Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis （SAP） in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ ...Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis （SAP） in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death, lts complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR （oxygen free radical）, endotoxin, etc. may play important roles in its progression.展开更多
AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to t...AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes.RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.展开更多
AIM： To observe the hepatic injury induced by carbon dioxide pneumoperitoneum in rats and to explore its potential mechanism.METHODS： Thirty healthy male SD rats were randomly divided into control group （n = 10）, ...AIM： To observe the hepatic injury induced by carbon dioxide pneumoperitoneum in rats and to explore its potential mechanism.METHODS： Thirty healthy male SD rats were randomly divided into control group （n = 10）, 0 h experimental group （n = 10） and 1 h experimental group （n = 10） after sham operation with carbon dioxide pneumoperitoneum. Histological changes in liver tissue were observed with hematoxylineosin staining. Liver function was assayed with an automatic biochemical analyzer. Concentration of malonyldialdehyde （MDA） and activity of superoxide dismutase （SOD） were assayed by colorimetry. Activity of adenine nucleotide translocator in liver tissue was detected with the atractyloside-inhibitor stop technique. Expression of hypoxia inducible factor-1 （HIF-1） mRNA in liver tissue was detected with in situ hybridization.RESULTS： Carbon dioxide 60 min could induce liver pneumoperitoneum for injury in rats. Alanine aminotransferase and aspartate aminotransferase were 95.7 ± 7.8 U/L and 86.8 ± 6.9 U/L in 0 h experimental group, and 101.4 ± 9.3 U/L and 106.6 ±8.7 U/L in 1 h experimental group. However, no significant difference was found in total billirubin, albumin, and pre-albumin in the three groups. In 0 h experimental group, the concentration of MDA was 9.83 ±2.53 μmol/g in liver homogenate and 7.64 ± 2.19 μmol/g in serum respectively, the activity of SOD was 67.58±9.75 nu/mg in liver and 64.47 ± 10.23 nu/mg in serum respectively. In 1 h experimental group, the concentration of MDA was 16.57±3.45 μmol/g in liver tissue and 12.49 ±4.21 μmol/g in serum respectively, the activity of SOD was 54.29 ±7.96 nu/mg in liver tissue and 56.31 ±9.85 nu/mg in serum respectively. The activity of ANT in liver tissue was 9.52 ± 1.56 in control group, 6.37± 1.33 in 0 h experimental group and 7.2 8±1.45 （10^-9 mol/min per gram protein） in 1 h experimental group, respectively. The expression of HIF-1 mRNA in liver tissue was not detected in control group, and its optical density difference value was 6.14±1.03 in 0 h experimental group and 9.51 ± 1.74 in 1 h experimental group, respectively. CONCLUSION： Carbon dioxide pneumoperitoneum during the sham operation can induce hepatic injury in rats. The probable mechanisms of liver injury include anoxia, ischemia reperfusion and oxidative stress. Liver injury should be avoided during clinical laparoscopic operation with carbon dioxide pneumoperitoneum.展开更多
Bergenin, isolated from the herb of Saxifrage stolonifera Curt.(Hu-Er-Cao) has hepatoprotective, anti-inflammatory, antitussive, and neuroprotective activities. The aim of the present study was to establish a simple, ...Bergenin, isolated from the herb of Saxifrage stolonifera Curt.(Hu-Er-Cao) has hepatoprotective, anti-inflammatory, antitussive, and neuroprotective activities. The aim of the present study was to establish a simple, rapid, and sensitive RP-HPLC method for determination of bergenin in rat plasma and compare its oral pharmacokinetic behaviors in normal and CCl_4-induced hepatic injury rats. With norisoboldine as an internal standard, chromatographic separation was performed on a C_(18) analytical column with acetonitrile and water(11 : 89, V/V) containing 0.1% formic acid as the mobile phase. A good linearity was obtained over the range of 100^(–1)0 000 ng·m L^(–1). The lower limit of quantification was 50 ng·m L~(^(–1)). The developed method was successfully applied to a study of the pharmacokinetic difference of bergenin(100 mg·kg^(–1)) between normal and hepatic injury rats after oral administration. Marked alterations of pharmacokinetic parameters in hepatic injury rats were observed. Compared to normal rats, the AUC_((0–∞)) of bergenin in hepatic injury rats was elevated to 2.11-fold and C_(max) was increased by 130%, whereas CL value was only 55% of the normal rats, suggesting that the systemic exposure of bergenin was significantly increased under hepatic injury status.展开更多
AIM:To observe the hepatic injury induced by carbon dioxide pneumoperitoneum(CDP) in rabbits,compare the eects olow-and high-pressure pneumoperitoneum,and to determine the degree o hepatic injury induced by these two ...AIM:To observe the hepatic injury induced by carbon dioxide pneumoperitoneum(CDP) in rabbits,compare the eects olow-and high-pressure pneumoperitoneum,and to determine the degree o hepatic injury induced by these two clinically relevant CDP pressures.METHODS:Thirty healthy male New Zealand rabbits weighing 3.0 to 3.5 kg were randomly divided into three groups(n = 10 for each group) and subjected to the ollowing to CDP pressures:no gas control,10 mmHg,or 15 mmHg.Histological changes in liver tissues were observed with hematoxylin and eosin staining and transmission electron microscopy.Liver unction was evaluated using an automatic biochemical analyzer.Adenine nucleotide translocator(ANT) activity in liver tissue was detected with the atractyloside-inhibitor stop technique.Bax and Bcl-2 expression levels were detected bywestern blotting.RESULTS:Liver Functions in the 10 mmHg and 15 mmHg experimental groups were significantly disturbed compared with the control group.After CDP,the levels or alanine transaminase and aspartate transaminase were 77.3 ± 14.5 IU/L and 60.1 ± 11.4 IU/L,respectively,in the 10 mmHg experimental group and 165.1 ± 19.4 IU/L and 103.8 ± 12.3 IU/L,respectively,in the 15 mmHg experimental group,which were all higher than those of the control group(p < 0.05).There was no difference in pre-albumin concentration between the 10 mmHg experimental group and the control group,but the prealbumin level of the 15 mmHg experimental group was significantly lower than that of the control group(p < 0.05).No significant differences were observed in the levels of total bilirubin or albumin among the three groups.After 30 and 60 min of CDP,pH was reduced(p < 0.05) and fa CO2 was elevated(p < 0.05) in the 10 mmHg group compared with controls,and these changes were more pronounced in the 15 mmHg group.Hematoxylin and eosin staining showed no significant change in liver morphology,except for mild hyperemia in the two experimental groups.Transmission electron microscopy showed mild mitochondrial swelling in hepatocytes of the 10 mmHg group,and this was more pronounced in the 15 mmHg group.No significant difference in ANT levels was found between the control and 10 mmHg groups.However,ANT concentration was significantly lower in the 15 mmHg group compared with the control group.The expression of hepatic Bax was significantly increased in the two experimental groups compared with the controls,but there were no differences in Bcl-2 levels among the three groups.Twelve hours after CDP induction,the expression of hepatic Bax was more significant in the 15 mmHg group than in the 10 mmHg group.CONCLUSION:A CDP pressure of 15 mmHg caused more substantial hepatic injury,such as increased levels of acidosis,mitochondrial damage,and apoptosis;therefore,10 mmHg CDP is preferable for laparoscopic operations.展开更多
AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombin...AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50μg/kg pcDNA3-ALR DNA.The effect of intravenous injection of recombinant pcDNA3ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid,the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P＜0.01).CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level ofAST and ALT in CCl4-intoxicated rats.展开更多
BACKGROUND:Stem cell transplantation provides a theoretical approach for liver regeneration medicine;it may promote liver regeneration and self-repair.However,the transplantation of bone marrow-mesenchymal stem cells ...BACKGROUND:Stem cell transplantation provides a theoretical approach for liver regeneration medicine;it may promote liver regeneration and self-repair.However,the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated.This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl 4 injury.METHODS:Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation,characterized by cytoflow immunofluorescence,and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl 4.The integration of bone marrow cells into the liver was examined microscopically,and plasma hepatic enzymes were determined biochemically.RESULTS:Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells.Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl 4-treated mice.Densitometry showed increased in situ cell proliferation(50±14 vs 20±3 cells/high-power field,P<0.05)and albumin expression(149±25 vs 20±5 cells/high-power field,P<0.05)in the liver,as well as reduced serum aminotransferase levels(P<0.05)and better survival rates(P<0.05)in animals receiving cultured bone marrow cells relative to controls.CONCLUSIONS:Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically-injured liver.Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.展开更多
AIM： To investigate apparent diffusion coefficient （ADC） values as an indication of reconditioning of acute hepatic injury （AHI） after allogeneic mononuclear bone marrow cell （MBMC） transplantation. METHODS： T...AIM： To investigate apparent diffusion coefficient （ADC） values as an indication of reconditioning of acute hepatic injury （AHI） after allogeneic mononuclear bone marrow cell （MBMC） transplantation. METHODS： Three groups were used in our study： a cell transplantation group （n = 21）, transplantation control group （n = 21） and normal control group （n = 10）. AHI model rabbits in the cell transplantation group were injected with 5 mL of MBMC suspension at multiple sites in the liver and the transplantation controls were injected with 5 mL D-Hanks solution. At the end of the 1st, 2nd and 4th wk, 7 rabbits were randomly selected from the cell transplantation group and trans- plantation control group for magnetic resonance diffu- sion-weighted imaging （MR-DWI） and measurement of the mean ADC values of injured livers. After MR-DWI examination, the rabbits were sacrificed and the livers subjected to pathological examination. Ten healthy rab- bits from the normal control group were used for MR- DWI examination and measurement of the mean ADC value of normal liver. RESULTS： At all time points, the liver pathological scores from the cell transplantation group were significantly lower than those in the transplantation control group （27.14± 1.46 vs 69.29± 6.16, 22.29 ± 2.29 vs 57.00± 1.53, 19.00 ± 2.31 vs 51.86 ± 6.04, P = 0.000）. The mean ADC values of the cell transplantation group were significantly higher than the transplantation con- trol group （（1.07± 0.07） ×10^-3 mm2/s vs （0.69 ± 0.05） ×10^-3 mm2/s, （1.41± 0.04） ×10^-3 mm2/s vs （0.84± 0.03） ×10^-3 mm2/s, （1.68 ± 0.04） ×10^-3 mm2/s vs （0.86± 0.04） ×10^-3 mm2/s, P = 0.000）. The pathological scores of the cell transplantation group and transplantation control group gradually decreased. However, their mean ADC values gradually increased to near that of the normal control. At the end of the 1st wk, the mean ADC values of the cell transplantation group and transplantation control group were significantly lower than those of the normal control group [（1.07 ± 0.07） ×10^-3 mm2/s vs （± 0.03） ×10^-3 mm2/s, （0.69± 0.05） ×10^-3 mm2/s vs （1.76 ± 0.03） ×10^-3 mm2/s, P = 0.000]. At any 2 time points, the pathological scores and the mean ADC values of the cell transplantation group were significantly different （P = 0.000）. At the end of the 1st wk, the pathological scores and the mean ADC values of the transplantation control group were significantly different from those at the end of the 2nd and 4th wk （P = 0.000）. However, there was no significant difference between the 2nd and 4th wk （P = 0.073 and 0.473, respectively）. The coefficient of correlation between the pathological score and the mean ADC value in the cell transplantation group was -0.883 （P = 0.000） and -0.762 （P = 0.000） in the transplantation control group. CONCLUSION： Tracking the longitudinally dynamic change in the mean ADC value of the AHI liver may reflect hepatic injury reconditioning after allogeneic MBMC transplantation.展开更多
N,N-Dimethylacetamide （DMAc） is a widely used organic solvent in modern chemical industry with low to moderate hepatotoxicity to occupational health of employees. But so far, there are fewer and less conclusive data...N,N-Dimethylacetamide （DMAc） is a widely used organic solvent in modern chemical industry with low to moderate hepatotoxicity to occupational health of employees. But so far, there are fewer and less conclusive data concerning its pathogenic mechanism in detail. In current study, the toxicity of DMAc was firstly investigated on human normal hepatocytes （LO-2）, using a series of molecular biology measurements to ananlyze the effect and mechanism of DMAc-induced hepatic cell injury and explore effective prophylactic measures. We found that DMAc triggered LO-2 apoptosis in a obviously dose-dependent manner, caused by increased ROS generation and activation of Bcl-2 pathway. Significantly, glutathione （GSH） rather than vitamin C （Vit C） could partially inhibit DMAc-induced apoptosis thus showing potential as a effective precaution for workers.展开更多
The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The ...The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.展开更多
AIM: To investigate the pharmacological effects of rice flavone (5,4'-dihydroxy-3',5'-dimethoxy-7-0-β-D-glucopyranosyloxy-flavone, RF) separated from panicle-differentiating to flowing rice on rat experim...AIM: To investigate the pharmacological effects of rice flavone (5,4'-dihydroxy-3',5'-dimethoxy-7-0-β-D-glucopyranosyloxy-flavone, RF) separated from panicle-differentiating to flowing rice on rat experimental hepatic injury. METHODS: Models of rat acute hepatic injury induced by carbon tetrachloride (CCl4) administration, rat hepatic fibrosis induced by thioacetamide, injury of primary cultured rat hepatocytes induced by CCl4, respectively, were established. After treated with RF, content of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and albumin (Alb), hyaluronic acid (HA), the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and hydroxyproline (Hyp) were measured and liver tissue was observed pathologically by hematoxylin-eosin (HE) staining. Effects of RF on pathological changes, function index, enzyme of scavenging free radicals and blood rheology were evaluated. RESULTS: In model of rat acute hepatic injury induced by CCI4, RF can significantly decrease the contents of serum ALT, AST, increase the content of Alb, improve the dropsy and fat denaturalization of hepatocytes. In model of rat hepatic fibrosis induced by thioacetamide, RF can inhibit the increase of HA, Hyp and whole blood viscosity, and improve the activities of GSH-Px and SOD, and inauricular microcirculation. CONCLUSION: RF has apparent protective effects on hepatic injury by increasing activity of GSH-Px and SOD, scavenging free radicals produced by CCI4, reducing blood viscosity, and improving microcirculation and blood supply.展开更多
Objective:To investigate color and microvascular blood flow of the tongue in the mini-swine with immune hepatic injury. Methods: Six Chinese mini-swine for experimental use, 3 males and 3 females, were randomly divide...Objective:To investigate color and microvascular blood flow of the tongue in the mini-swine with immune hepatic injury. Methods: Six Chinese mini-swine for experimental use, 3 males and 3 females, were randomly divided into two groups, normal group and model group, 3 swine in each group. The swine in the model group was administrated by injection of 5 mg/kg ConA into the vein of auricular back, once every other day, 3 times each week, for 2 weeks in total. The animal in the control group was administrated with equal volume of saline. At 9 o’clock in the morning of the 15th day of the experiment, each swine was anesthetized with intramuscular injection of 9 ml 2.5% pentobarbital sodium and 3 ml Maleate, and then picture of the tongue was taken, microvascular blood flow on the tongue and the liver was detected with a laser Doppler blood flowmeter; Blood was taken from the precaval vein. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST),total bilirubin (Tbil) and total protein (TP) were determined; Pathological changes of the liver and tongue tissues were investigated by means of HE staining; Serum TNF-α content was detected with ELISA assay. Results: In the mini-swine with immune hepatic injury induced by ConA, the tongue color showed cyanotic color, microvascular perfusion in the liver and the tongue, and partial pressure of oxygen in the tongue tissue significantly decreased; and the microcirculatory perfusion of the tongue was significantly correlated with that of the liver and the HIS color spatial value of the tongue; Serum TNF-α content significantly increased. Conclusion: The mini-swine with immune hepatic injury induced by ConA conforms to pathological characteristics of immune hepatic injury. Formation of the cyanotic tongue is related with microcirculatory disturbance of the tongue, which can indirectly reflect hepatic microcirculatory state in the immune hepatic injury.展开更多
To explore the protective effect of extract powder of turmeric on carbon tetrachloride （CCl4）-induced acute hepatic injury, the mice were administrated with extract powder of turmeric with different doses （50, 100,...To explore the protective effect of extract powder of turmeric on carbon tetrachloride （CCl4）-induced acute hepatic injury, the mice were administrated with extract powder of turmeric with different doses （50, 100, 200 mg/kg） for 7 d. Then the mice were treated with 0.12% CCl4 by intraperitoneal injection. The levels of ALT, AST in serum and activities of SOD, CAT, MDA, GSH-Px in liver tissue were detected and the liver lesions were examined. The results showed that the activities of ALT, AST and the level of MDA in extract powder of turmeric group were signif- icantly decreased, and the activities of SOD, CAT, GSH-Px were significantly increased, and liver pathology were improved compared with the injured group （P〈 0.05 or P〈0.01）. It indicated that the extract powder of turmeric had significant protective effect against CCl4 induced acute hepatic injury in mice.展开更多
BACKGROUND:Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice,but the underlying mechanisms remain obscure.The pre...BACKGROUND:Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice,but the underlying mechanisms remain obscure.The present study aimed to determine the relative roles of Th1 and Th17 type responses in concanavalin A-induced hepatic injury in mice,and to investigate whether or not Kupffer cells contribute to hepatic injury via a Th1 or Th17 type response-dependent pathway.METHODS:Immune-mediated hepatic injury was induced in C57BL/6 mice by intravenous injection of concanavalin A.Kupffer cells were inactivated by pretreatment with gadolinium chloride 24 hours before the concanavalin A injection.The interferon-gamma(IFN-γ)and interleukin-17(IL-17)pathways were blocked by specific neutralizing antibodies.Hepatic injury was assessed using serum transferase activity and pathological analysis.Expression of inflammatory cytokines within the liver was detected by real-time polymerase chain reaction and immunohistochemistry.RESULTS:Neutralization of IFN-γsignificantly attenuated concanavalin A-induced hepatic injury.However,neutralization of IL-17 failed to suppress the injury.Inactivation of Kupffer cells by gadolinium chloride pretreatment protected against concanavalin A-induced injury and significantly reduced hepatic cytokine levels including TNF-α,IL-6 and IFN-γbut not IL-17.CONCLUSION:Our findings suggest that Kupffer cells contribute to concanavalin A-induced hepatic injury via a Th1 type response-dependent pathway and production of inflammatory cytokines including TNF-α,IL-6 and IFN-γ.展开更多
AIM To develop a novel rat model of heterogeneous hepatic injury.METHODS Seventy male Sprague-Dawley rats were randomly divided into a control group(n = 10) and a colchicine group(n =60). A 0.25% colchicine solution(0...AIM To develop a novel rat model of heterogeneous hepatic injury.METHODS Seventy male Sprague-Dawley rats were randomly divided into a control group(n = 10) and a colchicine group(n =60). A 0.25% colchicine solution(0.4 mL/kg) was injected via the splenic vein in the colchicine group to develop a rat model of heterogeneous hepatic injury. An equal volume of normal saline was injected via the splenic vein in the control group. At days 3, 7, and 14 and weeks 4, 8, and 12 after the operation, at least seven rats of the colchicine group were selected randomly for magnetic resonance imaging(MRI) examinations, and then they were euthanized. Ten rats of the control group underwent MRI examinations at the same time points, and then were euthanized at week 12. T2-weighted images(T2 WI) and diffusion weighted imaging(DWI) were used to evaluate the heterogeneous hepatic injury. The heterogeneous injury between the left and right hepatic lobes was assessed on liver sections according to the histological scoring criteria, and correlated with the results of MRI study. RESULTS Obvious pathological changes occurred in the hepatic parenchyma in the colchicine group. Hepatic injury scores were significantly different between the left and right lobes at each time point(P < 0.05). There was a significant difference in apparent diffusion coefficient(ADC) of DWI and liver-to-muscle ratio(LMR) of T2 WI between the left and right lobes of rats in the colchicine group(P < 0.05) at each time point, and similar results were observed between the colchicine and control groups. Besides, there was a significant correlation between hepatic injury scores and ADC values or LMR(r =-0.682, P = 0.000; r =-0.245, P = 0.018).CONCLUSION Injection with colchicine via the splenic vein can be used to successfully develop a rat model of heterogeneous hepatic injury. DWI and T2 WI may help evaluate the heterogeneous injury among liver lobes.展开更多
Acute pancreatitis（AP） is characterized by its sudden onset and rapid progression and is often complicated by liver injury. APinduced liver injury may develop into hepatic failure and even result in death. Thus, it ...Acute pancreatitis（AP） is characterized by its sudden onset and rapid progression and is often complicated by liver injury. APinduced liver injury may develop into hepatic failure and even result in death. Thus, it is of importance to protect liver function and block injury-related pathways. In the pathogenesis of liver injury in AP, inflammatory cytokines, nuclear factor-kappa B（NF- κB） and oxygen free radicals play important roles. The complexity of the mechanism underlying the development of liver injury exerts, to some extent, a contribution to the difficulties in the treatment of this disease. Currently, the drugs used to treat the disease include L-arginine （L-Arg）, calcium ion antagonists, somatostatin and a variety of inflammatory mediator inhibitors. Additionally, some traditional Chinese medicines such as tfipterygium, wilfordii, rhubarb and salvia milfiorrhizae may also have some effects. In this article, the pathogenesis of liver injury in AP and its therapy are reviewed.展开更多
Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have ant...Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.展开更多
Summary： The regulating mechanism in hepatic injury caused by obstructive jaundice （OJ） was examined in this study. Rat hepatocytes were harvested by in situ collagenase perfusion and subjected to primary culture. ...Summary： The regulating mechanism in hepatic injury caused by obstructive jaundice （OJ） was examined in this study. Rat hepatocytes were harvested by in situ collagenase perfusion and subjected to primary culture. The heptocytes were pre-treated with various concentrations of protein kinase C （PKC） agonist PMA and its inhibitor chelerythrine and cultured for 20 min. After the treatment, 50μmol/L glycochenodeoxycholate （GCDC） was added and the cells were cultured for an additional 24 h. Cells were then detected by flow cytometry （FCM） and TUNEL. After hepatocytes were treated with different concentrations of fructose and 100μM GCDC, the cells were examined by FCM and TUNEL. Experimental obstructive jaundice （BDL） was induced by double ligation of the bile duct. After BDL, the rats were fed with or without fructos and sacrificed 3, 7, 14 and 21 days after the ligation. The apoptotic status was observed in liver of all rats with TUNEL and PKC protein in liver of OJ was studied by immunohistochemical method. Our results showed that PMA increased GCDC-induced apoptosis and chelerythrine decreased GCSX-induced apoptosis in a concentration-dependent manner. After the treatment with fructose of different concentrations, 100μM GCDC decreased the apoptotic rate and the apoptotic rate decreased with the increase of fructose concentration. The apoptotic rate of liver was related to the time of OJ. Without the treatment of fructose, PKC and apoptosis index （AI） were highest 14 days after the bile duct ligation. With the treatment of fructose, apoptosis index （AI） and PKC were decreased from the 14th day after the bile duct ligation. It is concluded that PKC is involved in the regulation of apoptosis in the liver cells with OJ and plays important roles in the development and progression of liver injury caused by OJ. Fructose can protect hepatocytes in the bile salt-induced apoptosis by regulating PKC.展开更多
Hepatic injury is rarely associated with undifferentiated connective tissue diseases (UCTD). We report, here, a case of a middle-aged woman with UCTD-related hepatic injury, including its case history, clinical manife...Hepatic injury is rarely associated with undifferentiated connective tissue diseases (UCTD). We report, here, a case of a middle-aged woman with UCTD-related hepatic injury, including its case history, clinical manifestations, laboratory findings, treatment and its short-term effect. The patient was admitted to the hospital with symptoms of fatigue, anorexia, low-grade fever and skin rashes. She had a past history of left knee joint replacement. Laboratory tests showed elevated levels of serum transaminase, IgG and globulin, accelerated erythrocyte sedimentation rate, eosinophilia and a high titer of antinuclear antibodies (1:320). Imaging studies showed interstitial pneumonitis and hydropericardium. Liver biopsy showed the features which were consistent with those of connective tissue diseases-related polyangitis. After treatment with a low-dose of oral prednisone, both symptoms and laboratory findings were significantly improved. UCTD-related hepatic injury should be considered in the differential diagnosis of connective tissue diseases with abnormal liver function tests. Low- dose prednisone may effectively improve both symptoms and laboratory tests.展开更多
BACKGROUND Hepatic ischemia-reperfusion injury(HIRI)remains one of the major causes of postoperative liver dysfunction following extensive hepatectomy and liver transplantation.Owing to its progressive and dynamic nat...BACKGROUND Hepatic ischemia-reperfusion injury(HIRI)remains one of the major causes of postoperative liver dysfunction following extensive hepatectomy and liver transplantation.Owing to its progressive and dynamic nature,HIRI may lead to multiple organ failure and a worsened outcome.Treprostinil is a relatively new synthetic prostacyclin analog with a potential beneficial effect against HIRI.Ischemic preconditioning(IP)is a promising method to protect against HIRI.AIM To investigate HIRI biomarkers,their effects on liver and heart,and the effects of treprostinil and IP on these processes.METHODS Forty male Wistar albino rats aged 3-4 months were randomly assigned to four groups of ten,subjected to a 3-hour surgical intervention,and then sacrificed.Hepatic ischemia was induced by clamping the hepatoduodenal ligament for 30 minutes,followed by reperfusion for 120 minutes.Treprostinil(100 ng/kg/minute for 24 hours)or IP before HIRI,no protection,and a sham operation were applied accordingly in each group.Liver and heart histopathology and specific serum and hepatic tissue biomarkers were assessed.RESULTS HIRI deteriorated hepatocellular function and exacerbated liver and myocardial damage in the control group.Furthermore,HIRI triggered cytokine overexpression and protein carbonyl content(P<0.001).Compared with those in the HIRI group,lower troponin I,tumor necrosis factor-α,endothelin-1,and interleukin-1βin serum and liver tissue were significantly correlated with reduced cellular necrosis and improved hepatocellular function in the treprostinil group(P<0.001).Similar but less pronounced effects were observed in the IP group.Both treprostinil and IP had protective effects in hepatic and cardiac tissues.However,treprostinil showed slightly superior cardioprotective efficacy,as evidenced by a statistically significant difference in troponin I levels(P<0.05)and histopathological scoring of myocardium samples,but there were no differences in the other parameters.CONCLUSION HIRI results in oxidative stress and cytokine overexpression,which deteriorate hepatic function and accelerates myocardial damage.Treprostinil and IP are promising strategies for preventing reperfusion-induced cellular and systemic damage.展开更多
基金Project supported by the Administration of Traditional Chinese Medicine of Zhejiang Province (Nos. 2003C130 and 2004C142)the Medical Science and Technology of Health Department of Zhejiang Province (No. 2003B134)the Technology and Development of Technological Bureau of Hangzhou (No. 2003123B19), China
文摘Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis （SAP） in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death, lts complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR （oxygen free radical）, endotoxin, etc. may play important roles in its progression.
基金Supported by Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang province, No. 2003C130 and No. 2004C142Foundation Project For Medical Science and Technology of Zhejiang province, No. 2003B134+3 种基金Grave Foundation Project for Technological and Development of Hangzhou, No. 2003123B19Intensive Foundation Project for Technology of Hangzhou, No. 2004Z006Foundation Project for Medical Science and Technology of Hangzhou, No. 2003A004Foundation Project for Technology of Hangzhou, No. 2005224
文摘AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes.RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.
基金Supported by The Eleventh-five Medical Science Fund of Chengdu Military Command Area,NoMB07011
文摘AIM： To observe the hepatic injury induced by carbon dioxide pneumoperitoneum in rats and to explore its potential mechanism.METHODS： Thirty healthy male SD rats were randomly divided into control group （n = 10）, 0 h experimental group （n = 10） and 1 h experimental group （n = 10） after sham operation with carbon dioxide pneumoperitoneum. Histological changes in liver tissue were observed with hematoxylineosin staining. Liver function was assayed with an automatic biochemical analyzer. Concentration of malonyldialdehyde （MDA） and activity of superoxide dismutase （SOD） were assayed by colorimetry. Activity of adenine nucleotide translocator in liver tissue was detected with the atractyloside-inhibitor stop technique. Expression of hypoxia inducible factor-1 （HIF-1） mRNA in liver tissue was detected with in situ hybridization.RESULTS： Carbon dioxide 60 min could induce liver pneumoperitoneum for injury in rats. Alanine aminotransferase and aspartate aminotransferase were 95.7 ± 7.8 U/L and 86.8 ± 6.9 U/L in 0 h experimental group, and 101.4 ± 9.3 U/L and 106.6 ±8.7 U/L in 1 h experimental group. However, no significant difference was found in total billirubin, albumin, and pre-albumin in the three groups. In 0 h experimental group, the concentration of MDA was 9.83 ±2.53 μmol/g in liver homogenate and 7.64 ± 2.19 μmol/g in serum respectively, the activity of SOD was 67.58±9.75 nu/mg in liver and 64.47 ± 10.23 nu/mg in serum respectively. In 1 h experimental group, the concentration of MDA was 16.57±3.45 μmol/g in liver tissue and 12.49 ±4.21 μmol/g in serum respectively, the activity of SOD was 54.29 ±7.96 nu/mg in liver tissue and 56.31 ±9.85 nu/mg in serum respectively. The activity of ANT in liver tissue was 9.52 ± 1.56 in control group, 6.37± 1.33 in 0 h experimental group and 7.2 8±1.45 （10^-9 mol/min per gram protein） in 1 h experimental group, respectively. The expression of HIF-1 mRNA in liver tissue was not detected in control group, and its optical density difference value was 6.14±1.03 in 0 h experimental group and 9.51 ± 1.74 in 1 h experimental group, respectively. CONCLUSION： Carbon dioxide pneumoperitoneum during the sham operation can induce hepatic injury in rats. The probable mechanisms of liver injury include anoxia, ischemia reperfusion and oxidative stress. Liver injury should be avoided during clinical laparoscopic operation with carbon dioxide pneumoperitoneum.
基金supported by Health Innovation Personnel Training Project of Changzhou City(No.CWKJ 2010-368)Changzhou High Level Health Personnel Training Project
文摘Bergenin, isolated from the herb of Saxifrage stolonifera Curt.(Hu-Er-Cao) has hepatoprotective, anti-inflammatory, antitussive, and neuroprotective activities. The aim of the present study was to establish a simple, rapid, and sensitive RP-HPLC method for determination of bergenin in rat plasma and compare its oral pharmacokinetic behaviors in normal and CCl_4-induced hepatic injury rats. With norisoboldine as an internal standard, chromatographic separation was performed on a C_(18) analytical column with acetonitrile and water(11 : 89, V/V) containing 0.1% formic acid as the mobile phase. A good linearity was obtained over the range of 100^(–1)0 000 ng·m L^(–1). The lower limit of quantification was 50 ng·m L~(^(–1)). The developed method was successfully applied to a study of the pharmacokinetic difference of bergenin(100 mg·kg^(–1)) between normal and hepatic injury rats after oral administration. Marked alterations of pharmacokinetic parameters in hepatic injury rats were observed. Compared to normal rats, the AUC_((0–∞)) of bergenin in hepatic injury rats was elevated to 2.11-fold and C_(max) was increased by 130%, whereas CL value was only 55% of the normal rats, suggesting that the systemic exposure of bergenin was significantly increased under hepatic injury status.
基金Supported by The Eleventh-five Medical Science Fund of Chengdu Military Command Area,No. MB07011China Post doctoral Science Foundation,No. 20100471764
文摘AIM:To observe the hepatic injury induced by carbon dioxide pneumoperitoneum(CDP) in rabbits,compare the eects olow-and high-pressure pneumoperitoneum,and to determine the degree o hepatic injury induced by these two clinically relevant CDP pressures.METHODS:Thirty healthy male New Zealand rabbits weighing 3.0 to 3.5 kg were randomly divided into three groups(n = 10 for each group) and subjected to the ollowing to CDP pressures:no gas control,10 mmHg,or 15 mmHg.Histological changes in liver tissues were observed with hematoxylin and eosin staining and transmission electron microscopy.Liver unction was evaluated using an automatic biochemical analyzer.Adenine nucleotide translocator(ANT) activity in liver tissue was detected with the atractyloside-inhibitor stop technique.Bax and Bcl-2 expression levels were detected bywestern blotting.RESULTS:Liver Functions in the 10 mmHg and 15 mmHg experimental groups were significantly disturbed compared with the control group.After CDP,the levels or alanine transaminase and aspartate transaminase were 77.3 ± 14.5 IU/L and 60.1 ± 11.4 IU/L,respectively,in the 10 mmHg experimental group and 165.1 ± 19.4 IU/L and 103.8 ± 12.3 IU/L,respectively,in the 15 mmHg experimental group,which were all higher than those of the control group(p < 0.05).There was no difference in pre-albumin concentration between the 10 mmHg experimental group and the control group,but the prealbumin level of the 15 mmHg experimental group was significantly lower than that of the control group(p < 0.05).No significant differences were observed in the levels of total bilirubin or albumin among the three groups.After 30 and 60 min of CDP,pH was reduced(p < 0.05) and fa CO2 was elevated(p < 0.05) in the 10 mmHg group compared with controls,and these changes were more pronounced in the 15 mmHg group.Hematoxylin and eosin staining showed no significant change in liver morphology,except for mild hyperemia in the two experimental groups.Transmission electron microscopy showed mild mitochondrial swelling in hepatocytes of the 10 mmHg group,and this was more pronounced in the 15 mmHg group.No significant difference in ANT levels was found between the control and 10 mmHg groups.However,ANT concentration was significantly lower in the 15 mmHg group compared with the control group.The expression of hepatic Bax was significantly increased in the two experimental groups compared with the controls,but there were no differences in Bcl-2 levels among the three groups.Twelve hours after CDP induction,the expression of hepatic Bax was more significant in the 15 mmHg group than in the 10 mmHg group.CONCLUSION:A CDP pressure of 15 mmHg caused more substantial hepatic injury,such as increased levels of acidosis,mitochondrial damage,and apoptosis;therefore,10 mmHg CDP is preferable for laparoscopic operations.
基金Supported by the Natural Science Foundation of Hebei Province, No. 302489
文摘AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50μg/kg pcDNA3-ALR DNA.The effect of intravenous injection of recombinant pcDNA3ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid,the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P＜0.01).CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level ofAST and ALT in CCl4-intoxicated rats.
基金supported in part by a grant from the Project of Science and Technology Research from the Education Bureau of Heilongjiang Province,China(11551245)
文摘BACKGROUND:Stem cell transplantation provides a theoretical approach for liver regeneration medicine;it may promote liver regeneration and self-repair.However,the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated.This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl 4 injury.METHODS:Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation,characterized by cytoflow immunofluorescence,and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl 4.The integration of bone marrow cells into the liver was examined microscopically,and plasma hepatic enzymes were determined biochemically.RESULTS:Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells.Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl 4-treated mice.Densitometry showed increased in situ cell proliferation(50±14 vs 20±3 cells/high-power field,P<0.05)and albumin expression(149±25 vs 20±5 cells/high-power field,P<0.05)in the liver,as well as reduced serum aminotransferase levels(P<0.05)and better survival rates(P<0.05)in animals receiving cultured bone marrow cells relative to controls.CONCLUSIONS:Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically-injured liver.Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.
基金Supported by The National Natural Science Foundation of China,No. 30070235,No. 30470508 and No. 30870695The Natural Science Foundation of Hunan Province,No. 06JJ2008,07JJ6040
文摘AIM： To investigate apparent diffusion coefficient （ADC） values as an indication of reconditioning of acute hepatic injury （AHI） after allogeneic mononuclear bone marrow cell （MBMC） transplantation. METHODS： Three groups were used in our study： a cell transplantation group （n = 21）, transplantation control group （n = 21） and normal control group （n = 10）. AHI model rabbits in the cell transplantation group were injected with 5 mL of MBMC suspension at multiple sites in the liver and the transplantation controls were injected with 5 mL D-Hanks solution. At the end of the 1st, 2nd and 4th wk, 7 rabbits were randomly selected from the cell transplantation group and trans- plantation control group for magnetic resonance diffu- sion-weighted imaging （MR-DWI） and measurement of the mean ADC values of injured livers. After MR-DWI examination, the rabbits were sacrificed and the livers subjected to pathological examination. Ten healthy rab- bits from the normal control group were used for MR- DWI examination and measurement of the mean ADC value of normal liver. RESULTS： At all time points, the liver pathological scores from the cell transplantation group were significantly lower than those in the transplantation control group （27.14± 1.46 vs 69.29± 6.16, 22.29 ± 2.29 vs 57.00± 1.53, 19.00 ± 2.31 vs 51.86 ± 6.04, P = 0.000）. The mean ADC values of the cell transplantation group were significantly higher than the transplantation con- trol group （（1.07± 0.07） ×10^-3 mm2/s vs （0.69 ± 0.05） ×10^-3 mm2/s, （1.41± 0.04） ×10^-3 mm2/s vs （0.84± 0.03） ×10^-3 mm2/s, （1.68 ± 0.04） ×10^-3 mm2/s vs （0.86± 0.04） ×10^-3 mm2/s, P = 0.000）. The pathological scores of the cell transplantation group and transplantation control group gradually decreased. However, their mean ADC values gradually increased to near that of the normal control. At the end of the 1st wk, the mean ADC values of the cell transplantation group and transplantation control group were significantly lower than those of the normal control group [（1.07 ± 0.07） ×10^-3 mm2/s vs （± 0.03） ×10^-3 mm2/s, （0.69± 0.05） ×10^-3 mm2/s vs （1.76 ± 0.03） ×10^-3 mm2/s, P = 0.000]. At any 2 time points, the pathological scores and the mean ADC values of the cell transplantation group were significantly different （P = 0.000）. At the end of the 1st wk, the pathological scores and the mean ADC values of the transplantation control group were significantly different from those at the end of the 2nd and 4th wk （P = 0.000）. However, there was no significant difference between the 2nd and 4th wk （P = 0.073 and 0.473, respectively）. The coefficient of correlation between the pathological score and the mean ADC value in the cell transplantation group was -0.883 （P = 0.000） and -0.762 （P = 0.000） in the transplantation control group. CONCLUSION： Tracking the longitudinally dynamic change in the mean ADC value of the AHI liver may reflect hepatic injury reconditioning after allogeneic MBMC transplantation.
基金supported by Jiangsu Province’s Outstanding Medical Academic Leader Program(LJ201130)
文摘N,N-Dimethylacetamide （DMAc） is a widely used organic solvent in modern chemical industry with low to moderate hepatotoxicity to occupational health of employees. But so far, there are fewer and less conclusive data concerning its pathogenic mechanism in detail. In current study, the toxicity of DMAc was firstly investigated on human normal hepatocytes （LO-2）, using a series of molecular biology measurements to ananlyze the effect and mechanism of DMAc-induced hepatic cell injury and explore effective prophylactic measures. We found that DMAc triggered LO-2 apoptosis in a obviously dose-dependent manner, caused by increased ROS generation and activation of Bcl-2 pathway. Significantly, glutathione （GSH） rather than vitamin C （Vit C） could partially inhibit DMAc-induced apoptosis thus showing potential as a effective precaution for workers.
文摘The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.
基金Supported by the National Natural Science Foundation of China, No. 30170105
文摘AIM: To investigate the pharmacological effects of rice flavone (5,4'-dihydroxy-3',5'-dimethoxy-7-0-β-D-glucopyranosyloxy-flavone, RF) separated from panicle-differentiating to flowing rice on rat experimental hepatic injury. METHODS: Models of rat acute hepatic injury induced by carbon tetrachloride (CCl4) administration, rat hepatic fibrosis induced by thioacetamide, injury of primary cultured rat hepatocytes induced by CCl4, respectively, were established. After treated with RF, content of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and albumin (Alb), hyaluronic acid (HA), the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and hydroxyproline (Hyp) were measured and liver tissue was observed pathologically by hematoxylin-eosin (HE) staining. Effects of RF on pathological changes, function index, enzyme of scavenging free radicals and blood rheology were evaluated. RESULTS: In model of rat acute hepatic injury induced by CCI4, RF can significantly decrease the contents of serum ALT, AST, increase the content of Alb, improve the dropsy and fat denaturalization of hepatocytes. In model of rat hepatic fibrosis induced by thioacetamide, RF can inhibit the increase of HA, Hyp and whole blood viscosity, and improve the activities of GSH-Px and SOD, and inauricular microcirculation. CONCLUSION: RF has apparent protective effects on hepatic injury by increasing activity of GSH-Px and SOD, scavenging free radicals produced by CCI4, reducing blood viscosity, and improving microcirculation and blood supply.
基金supported by a grant from Beijing Municipal Personnel and Organization Ministry (No.20071D0501800247)Natural Science Grant of Capital Medical University (No.2006ZR01)
文摘Objective:To investigate color and microvascular blood flow of the tongue in the mini-swine with immune hepatic injury. Methods: Six Chinese mini-swine for experimental use, 3 males and 3 females, were randomly divided into two groups, normal group and model group, 3 swine in each group. The swine in the model group was administrated by injection of 5 mg/kg ConA into the vein of auricular back, once every other day, 3 times each week, for 2 weeks in total. The animal in the control group was administrated with equal volume of saline. At 9 o’clock in the morning of the 15th day of the experiment, each swine was anesthetized with intramuscular injection of 9 ml 2.5% pentobarbital sodium and 3 ml Maleate, and then picture of the tongue was taken, microvascular blood flow on the tongue and the liver was detected with a laser Doppler blood flowmeter; Blood was taken from the precaval vein. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST),total bilirubin (Tbil) and total protein (TP) were determined; Pathological changes of the liver and tongue tissues were investigated by means of HE staining; Serum TNF-α content was detected with ELISA assay. Results: In the mini-swine with immune hepatic injury induced by ConA, the tongue color showed cyanotic color, microvascular perfusion in the liver and the tongue, and partial pressure of oxygen in the tongue tissue significantly decreased; and the microcirculatory perfusion of the tongue was significantly correlated with that of the liver and the HIS color spatial value of the tongue; Serum TNF-α content significantly increased. Conclusion: The mini-swine with immune hepatic injury induced by ConA conforms to pathological characteristics of immune hepatic injury. Formation of the cyanotic tongue is related with microcirculatory disturbance of the tongue, which can indirectly reflect hepatic microcirculatory state in the immune hepatic injury.
基金Supported by the Scientific and Technological Innovation Project of Wuhan Academy of Agricultural Science&Technology(CX201417)~~
文摘To explore the protective effect of extract powder of turmeric on carbon tetrachloride （CCl4）-induced acute hepatic injury, the mice were administrated with extract powder of turmeric with different doses （50, 100, 200 mg/kg） for 7 d. Then the mice were treated with 0.12% CCl4 by intraperitoneal injection. The levels of ALT, AST in serum and activities of SOD, CAT, MDA, GSH-Px in liver tissue were detected and the liver lesions were examined. The results showed that the activities of ALT, AST and the level of MDA in extract powder of turmeric group were signif- icantly decreased, and the activities of SOD, CAT, GSH-Px were significantly increased, and liver pathology were improved compared with the injured group （P〈 0.05 or P〈0.01）. It indicated that the extract powder of turmeric had significant protective effect against CCl4 induced acute hepatic injury in mice.
基金supported by grants from the National Basic Research Program of China(973 Program)(2009CB522403)the Key Program of the National Natural Science Foundation of China(30730085)the National Natural Science Youth Foundation of China(J20090846)
文摘BACKGROUND:Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice,but the underlying mechanisms remain obscure.The present study aimed to determine the relative roles of Th1 and Th17 type responses in concanavalin A-induced hepatic injury in mice,and to investigate whether or not Kupffer cells contribute to hepatic injury via a Th1 or Th17 type response-dependent pathway.METHODS:Immune-mediated hepatic injury was induced in C57BL/6 mice by intravenous injection of concanavalin A.Kupffer cells were inactivated by pretreatment with gadolinium chloride 24 hours before the concanavalin A injection.The interferon-gamma(IFN-γ)and interleukin-17(IL-17)pathways were blocked by specific neutralizing antibodies.Hepatic injury was assessed using serum transferase activity and pathological analysis.Expression of inflammatory cytokines within the liver was detected by real-time polymerase chain reaction and immunohistochemistry.RESULTS:Neutralization of IFN-γsignificantly attenuated concanavalin A-induced hepatic injury.However,neutralization of IL-17 failed to suppress the injury.Inactivation of Kupffer cells by gadolinium chloride pretreatment protected against concanavalin A-induced injury and significantly reduced hepatic cytokine levels including TNF-α,IL-6 and IFN-γbut not IL-17.CONCLUSION:Our findings suggest that Kupffer cells contribute to concanavalin A-induced hepatic injury via a Th1 type response-dependent pathway and production of inflammatory cytokines including TNF-α,IL-6 and IFN-γ.
基金Supported by the Chinese National Natural Science Foundation,No.81471719
文摘AIM To develop a novel rat model of heterogeneous hepatic injury.METHODS Seventy male Sprague-Dawley rats were randomly divided into a control group(n = 10) and a colchicine group(n =60). A 0.25% colchicine solution(0.4 mL/kg) was injected via the splenic vein in the colchicine group to develop a rat model of heterogeneous hepatic injury. An equal volume of normal saline was injected via the splenic vein in the control group. At days 3, 7, and 14 and weeks 4, 8, and 12 after the operation, at least seven rats of the colchicine group were selected randomly for magnetic resonance imaging(MRI) examinations, and then they were euthanized. Ten rats of the control group underwent MRI examinations at the same time points, and then were euthanized at week 12. T2-weighted images(T2 WI) and diffusion weighted imaging(DWI) were used to evaluate the heterogeneous hepatic injury. The heterogeneous injury between the left and right hepatic lobes was assessed on liver sections according to the histological scoring criteria, and correlated with the results of MRI study. RESULTS Obvious pathological changes occurred in the hepatic parenchyma in the colchicine group. Hepatic injury scores were significantly different between the left and right lobes at each time point(P < 0.05). There was a significant difference in apparent diffusion coefficient(ADC) of DWI and liver-to-muscle ratio(LMR) of T2 WI between the left and right lobes of rats in the colchicine group(P < 0.05) at each time point, and similar results were observed between the colchicine and control groups. Besides, there was a significant correlation between hepatic injury scores and ADC values or LMR(r =-0.682, P = 0.000; r =-0.245, P = 0.018).CONCLUSION Injection with colchicine via the splenic vein can be used to successfully develop a rat model of heterogeneous hepatic injury. DWI and T2 WI may help evaluate the heterogeneous injury among liver lobes.
基金technological foundation project of Tradi-tional Chinese Medicine Science of Zhejiang province(NO.2003C130 NO.2004C142)+4 种基金foundation project for medical science and technology of Zhejiang province(NO.2003B134)grave foundation project for tech-nological and development of Hangzhou(NO.2003123B19)intensive foundation project for technology of Hangzhou(NO.2004Z006)foundation project for medical science and technology of Hangzhou(No.2003A004)foundation project for technology of Hangzhou(NO.2005224)
文摘Acute pancreatitis（AP） is characterized by its sudden onset and rapid progression and is often complicated by liver injury. APinduced liver injury may develop into hepatic failure and even result in death. Thus, it is of importance to protect liver function and block injury-related pathways. In the pathogenesis of liver injury in AP, inflammatory cytokines, nuclear factor-kappa B（NF- κB） and oxygen free radicals play important roles. The complexity of the mechanism underlying the development of liver injury exerts, to some extent, a contribution to the difficulties in the treatment of this disease. Currently, the drugs used to treat the disease include L-arginine （L-Arg）, calcium ion antagonists, somatostatin and a variety of inflammatory mediator inhibitors. Additionally, some traditional Chinese medicines such as tfipterygium, wilfordii, rhubarb and salvia milfiorrhizae may also have some effects. In this article, the pathogenesis of liver injury in AP and its therapy are reviewed.
基金supported by the Russian Foundation for Basic Research (Grant No. 20-04-00526А)
文摘Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.
文摘Summary： The regulating mechanism in hepatic injury caused by obstructive jaundice （OJ） was examined in this study. Rat hepatocytes were harvested by in situ collagenase perfusion and subjected to primary culture. The heptocytes were pre-treated with various concentrations of protein kinase C （PKC） agonist PMA and its inhibitor chelerythrine and cultured for 20 min. After the treatment, 50μmol/L glycochenodeoxycholate （GCDC） was added and the cells were cultured for an additional 24 h. Cells were then detected by flow cytometry （FCM） and TUNEL. After hepatocytes were treated with different concentrations of fructose and 100μM GCDC, the cells were examined by FCM and TUNEL. Experimental obstructive jaundice （BDL） was induced by double ligation of the bile duct. After BDL, the rats were fed with or without fructos and sacrificed 3, 7, 14 and 21 days after the ligation. The apoptotic status was observed in liver of all rats with TUNEL and PKC protein in liver of OJ was studied by immunohistochemical method. Our results showed that PMA increased GCDC-induced apoptosis and chelerythrine decreased GCSX-induced apoptosis in a concentration-dependent manner. After the treatment with fructose of different concentrations, 100μM GCDC decreased the apoptotic rate and the apoptotic rate decreased with the increase of fructose concentration. The apoptotic rate of liver was related to the time of OJ. Without the treatment of fructose, PKC and apoptosis index （AI） were highest 14 days after the bile duct ligation. With the treatment of fructose, apoptosis index （AI） and PKC were decreased from the 14th day after the bile duct ligation. It is concluded that PKC is involved in the regulation of apoptosis in the liver cells with OJ and plays important roles in the development and progression of liver injury caused by OJ. Fructose can protect hepatocytes in the bile salt-induced apoptosis by regulating PKC.
文摘Hepatic injury is rarely associated with undifferentiated connective tissue diseases (UCTD). We report, here, a case of a middle-aged woman with UCTD-related hepatic injury, including its case history, clinical manifestations, laboratory findings, treatment and its short-term effect. The patient was admitted to the hospital with symptoms of fatigue, anorexia, low-grade fever and skin rashes. She had a past history of left knee joint replacement. Laboratory tests showed elevated levels of serum transaminase, IgG and globulin, accelerated erythrocyte sedimentation rate, eosinophilia and a high titer of antinuclear antibodies (1:320). Imaging studies showed interstitial pneumonitis and hydropericardium. Liver biopsy showed the features which were consistent with those of connective tissue diseases-related polyangitis. After treatment with a low-dose of oral prednisone, both symptoms and laboratory findings were significantly improved. UCTD-related hepatic injury should be considered in the differential diagnosis of connective tissue diseases with abnormal liver function tests. Low- dose prednisone may effectively improve both symptoms and laboratory tests.
文摘BACKGROUND Hepatic ischemia-reperfusion injury(HIRI)remains one of the major causes of postoperative liver dysfunction following extensive hepatectomy and liver transplantation.Owing to its progressive and dynamic nature,HIRI may lead to multiple organ failure and a worsened outcome.Treprostinil is a relatively new synthetic prostacyclin analog with a potential beneficial effect against HIRI.Ischemic preconditioning(IP)is a promising method to protect against HIRI.AIM To investigate HIRI biomarkers,their effects on liver and heart,and the effects of treprostinil and IP on these processes.METHODS Forty male Wistar albino rats aged 3-4 months were randomly assigned to four groups of ten,subjected to a 3-hour surgical intervention,and then sacrificed.Hepatic ischemia was induced by clamping the hepatoduodenal ligament for 30 minutes,followed by reperfusion for 120 minutes.Treprostinil(100 ng/kg/minute for 24 hours)or IP before HIRI,no protection,and a sham operation were applied accordingly in each group.Liver and heart histopathology and specific serum and hepatic tissue biomarkers were assessed.RESULTS HIRI deteriorated hepatocellular function and exacerbated liver and myocardial damage in the control group.Furthermore,HIRI triggered cytokine overexpression and protein carbonyl content(P<0.001).Compared with those in the HIRI group,lower troponin I,tumor necrosis factor-α,endothelin-1,and interleukin-1βin serum and liver tissue were significantly correlated with reduced cellular necrosis and improved hepatocellular function in the treprostinil group(P<0.001).Similar but less pronounced effects were observed in the IP group.Both treprostinil and IP had protective effects in hepatic and cardiac tissues.However,treprostinil showed slightly superior cardioprotective efficacy,as evidenced by a statistically significant difference in troponin I levels(P<0.05)and histopathological scoring of myocardium samples,but there were no differences in the other parameters.CONCLUSION HIRI results in oxidative stress and cytokine overexpression,which deteriorate hepatic function and accelerates myocardial damage.Treprostinil and IP are promising strategies for preventing reperfusion-induced cellular and systemic damage.
