AIM： To build up the research models of hepatic fibrosis in mice.METHODS： Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate （ANIT）, allyl alcohol （AA）,carbon tetrachloride （CCl4...AIM： To build up the research models of hepatic fibrosis in mice.METHODS： Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate （ANIT）, allyl alcohol （AA）,carbon tetrachloride （CCl4）, 3,5-diethoxycarbonyl-l,4-dihydrocollidine （DDC）, and silica, or subjected to common bile duct ligation （CBDL） to induce hepatic injury. Liver biopsies were performed every 4 wk to evaluate hepatic fibrosis over a period of 6 mo. Cumulative cirrhosis and survival curves were constructed by life table method and compared with Wilcoxon test.RESULTS： Under the dosages used, there was neither mortality nor cirrhosis in AA and silica-treated groups. DDC and ANIT caused cirrhosis within 4-12 and 12-24 wk, respectively.Both showed significantly faster cirrhosis induction at high dosages without significant alteration of survival. The duration for cirrhosis induction by CCl4 ranged from 4 to 20 wk, mainly dependent upon the dosage. However, the increase in CCl4 dosage significantly worsened survival. Intraperitoneal CCl4 administration resulted in better survival in comparison with garage administration at high dosage, but not at medium and low dosages. After CBDL, all the mice developed liver cirrhosis within 4-8 wk and then died by the end of 26 wk.CONCLUSION： CBDL and administrations of ANIT, CCl4, and DDC ensured liver cirrhosis. CBDL required the least amount of time in cirrhosis induction, but caused shortened lives of mice. It was followed by DDC and ANIT administration with favorable survival. As for CCl4, the speed of cirrhosis induction and the mouse survival depended upon the dosages and the administration route.展开更多
Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligatio...Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Methods Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. Results There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Conclusion Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis.展开更多
AIM： To investigate the effects of heme oxygenase-1 （HO-1） against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either cobalt protoporphyrin （CoPP）, a HO-1 inducer, or saline were injecte...AIM： To investigate the effects of heme oxygenase-1 （HO-1） against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either cobalt protoporphyrin （CoPP）, a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and q/tokine and collagen- Iα （Col- I α） mRNA expression was detected using RNase protection assays.RESULTS： Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius redpositive areas were increased to about 11.7% after BDL. Collagen-1 α and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression.CONCLUSION： Hepatic fibrosis due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1 overexpression increases liver injury in rats under conditions of experimental chronic cholestasis.展开更多
Objective:To evaluate the possible protective effect of Citrus aurantium peel extract(CAE)against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice.Methods:Male ICR mice were divided to 5 g...Objective:To evaluate the possible protective effect of Citrus aurantium peel extract(CAE)against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice.Methods:Male ICR mice were divided to 5 groups:1)Control group(Sham-operated mice),2)Cholestatic liver injury group induced by bile duct ligation(BDL),3)BDL mice treated with silymarin(200 mg/kg)for 4 weeks,4)BDL mice treated with 50 mg/kg CAE for 4 weeks,5)BDL mice treated with 200 mg/kg CAE for 4 weeks.Mice were sacrificed and liver fibrosis was evaluated by serum and hepatic tissue biochemistry tests and liver histopathological examination.Effects of CAE on inflammation and apoptosis gene regulation were investigated through real-time PCR.CAE effect on lipid metabolism related signaling was determined by western blot analysis.Results:In BDL mice,administration of CAE for 4 weeks markedly attenuated liver fibrosis based on histopathological alteration.Serum and hepatic tissue biochemistry results revealed that CAE(50 and 200 mg/kg)decreased the levels of alanine transaminase,aspartate transaminase,gamma glutamyl transferase,total bilirubin,nitric oxide,and thiobarbituric acid reactive substances.Real-time PCR and western blot analysis showed that CAE regulated inflammation,apoptosis,and lipid metabolism factors increased by BDL.Interleukin family,tumor necrosis factorα,and related apoptosis factors m RNA levels were increased by BDL treatment.However,these increases were suppressed by CAE administration.In addition,CAE effectively increased phosphorylation of AMPactivated protein kinase,nuclear factor E2-related factor 2,and related cytoprotective proteins.Conclusions:CAE can efficiently regulate BDL-induced liver injury with antioxidant,antiinflammatory,and antiapoptotic activities.展开更多
The epididymis is divided into caput, corpus and cauda regions, organized into intraregional segments separated by connective tissue septa （CTS）. In the adult rat and mouse these segments are highly differentiated. ...The epididymis is divided into caput, corpus and cauda regions, organized into intraregional segments separated by connective tissue septa （CTS）. In the adult rat and mouse these segments are highly differentiated. Regulation of these segments is by endocrine, lumicrine and paracrine factors, the relative importance of which remains under investigation. Here, the ability of the CTS to limit signaling in the interstitial compartment is reviewed as is the effect of 15 days of unilateral efferent duct ligation （EDL） on ipsilateral segmental transcriptional profiles. Inter-segmental microperifusions of epidermal growth factor （EGF）, vascular endothelial growth factor （VEGFA） and fibroblast growth factor 2 （FGF2） increased phosphorylation of mitogen activated protein kinase （MAPK） in segments 1 and 2 of the rat epididymis and the effects of all factors were limited by the CTS separating the segments. Microan＇ay analysis of segmental gene expression determined the effect of 15 days of unilateral EDL on the transcriptome-wide gene expression of rat segments 1-4. Over 11 000 genes were expressed in each of the four segments and over 2 000 transcripts in segment 1 responded to deprivation of testicular lumicrine factors. Segments 1 and 2 of control tissues were the most transcriptionally different and EDL had its greatest effects there. In the absence of lumicrine factors, all four segments regressed to a transcriptionally undifferentiated state, consistent with the less differentiated histology. Deprivation of lumicrine factors could stimulate an individual gene＇s expression in some segments yet suppress it in others. Such results reveal a higher complexity of the regulation of rat epididymal segments than that is generally appreciated. （Asian J Androl 2007 July; 9： 565-573）展开更多
AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. METHODS: A total of 40 male Sprague-Dawley rats, weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 1...AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. METHODS: A total of 40 male Sprague-Dawley rats, weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 10) rats underwent laparotomy alone and the bile duct was just dissected from the surrounding tissue. Group 2 rats (untreated, n = 10) were subjected to bile duct ligation (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats (high-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. At the end of the two-week period, biochemical and histological evaluations were processed. RESULTS: The mean serum bilirubin and liver enzyme levels signifi cantly decreased, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) values were significantly increased in low-dose dexa and high-dose dexa groups when compared to the untreated group. The histopathological score was significantly less in the low-dose and high-dose dexa groups compared to the untreated rats. In the low-dose dexa group, moderate liver damage was seen, while mild liver damage was observed in the high-dose dexa group. CONCLUSION: Corticosteroids reduced liver damage produced by bile duct obstruction. However, the histopathological score was not signifi cantly lower in the high-dose corticosteroid group as compared to the low-dose group. Thus, low-dose corticosteroid provides asignifi cant reduction of liver damage without increased side effects, while high dose is associated not with lower fi brosis but with increased side effects.展开更多
AIM： To investigate the effects of （dietary） glycine against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawl...AIM： To investigate the effects of （dietary） glycine against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawley （SD） rats. Three days later, BDL or sham-operation was performed. Rats were sacrificed 1 to 3 d after BDL. The influence of deoxycholic acid （DCA） in the presence or absence of glycine on liver cells was determined by measurement of calcium and chloride influx in cultivated Kupffer cells and lactate dehydrogenase （LDH） activity was determined in the supernatant of cultivated hepatocytes.RESULTS： Serum alanine transaminase levels increased to about 600 U/L 1 d alter BDL. However, enzyme release was blunted by about two third in rats receiving glycine. Release of the alkaline phosphatase and aspartate aminotransferase was also blocked significantly in the group fed glycine. Focal necrosis was observed 2 d after BDL. Glycine partially blocked the histopathological changes. Incubation of Kupffer cells with DCA led to increased intracellular calcium that could be blocked by incubation with glycine. However, systemic blockage of Kupffer cells with gadolinium chloride had no effects on transaminase release. Incubation of isolated hepatocytes with DCA led to a significant release of LDH after 4 h. This release was largely blocked when incubation with glycine was performed.CONCLUSION： These data indicate that glycine significantly decreased liver injury, most likely by a direct effect on hepatocytes. Kupffer cells do not appear to play an important role in the pathological changes caused by cholestasis.展开更多
BACKGROUND Bile duct ligation(BDL)in animals is a classical method for mimicking cholestatic fibrosis.Although different surgical techniques have been described in rats and rabbits,mouse models can be more cost-effect...BACKGROUND Bile duct ligation(BDL)in animals is a classical method for mimicking cholestatic fibrosis.Although different surgical techniques have been described in rats and rabbits,mouse models can be more cost-effective and reproducible for investigating cholestatic fibrosis.Magnetic resonance imaging(MRI)has made great advances for noninvasive assessment of liver fibrosis.More comprehensive liver fibrotic features of BDL on MRI are important.However,the utility of multiparameter MRI to detect liver fibrosis in a BDL mouse model has not been assessed.AIM To evaluate the correlation between the pathological changes and multiparameter MRI characteristics of liver fibrosis in a BDL mouse model.METHODS Twenty-eight healthy adult male balb/c mice were randomly divided into four groups:sham,week 2 BDL,week 4 BDL,and week 6 BDL.Multiparameter MRI sequences,included magnetic resonance cholangiopancreatography,T1-weighted,T2-weighted,T2 mapping,and pre-and post-enhanced T1 mapping,were performed after sham and BDL surgery.Peripheral blood and liver tissue were collected after MRI.For statistical analysis,Student’s t-test and Pearson’s correlation coefficient were used.RESULTS Four mice died after BDL surgery;seven,six,five and six mice were included separately from the four groups.Signal intensities of liver parenchyma showed no difference on TI-and T2-weighted images.Bile duct volume,ΔT1 value,T2 value,and the rate of liver fibrosis increased steadily in week 2 BDL,week 4 BDL and week 6 BDL groups compared with those in the sham group(P<0.01).Alanine aminotransferase and aspartate transaminase levels initially surged after surgery,followed by a gradual decline over time.Strong correlations were found between bile duct volume(r=0.84),T2 value(r=0.78),ΔT1 value(r=0.62),and hepatic fibrosis rate(all P<0.01)in the BDL groups.CONCLUSION The BDL mouse model induces changes that can be observed on MRI.The MRI parameters correlate with the hepatic fibrosis rate and allow for detection of cholestatic fibrosis.展开更多
Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal...Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal Oct expressions using bile duct ligation(BDL)rats.Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure,associated with decreased intestinal absorption and increased urinary excretion.Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2.In vitro cell experiments show that chenodeoxycholic acid(CDCA),bilirubin and farnesoid X receptor(FXR)agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1,which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR.Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL,which are confirmed using CDCA-treated and bilirubin-treated rats.A disease-based physiologically based pharmacokinetic model characterizing intestinal,hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats.In conclusion,BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats,finally,decreasing plasma exposure and impairing hypoglycemic effects of metformin.BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.展开更多
Hepatectomy is an effective surgical treatment for multiple bilobar liver metastases from colon cancer;however,one of the primary obstacles to completing surgical resection for these cases is an insufficient volume of...Hepatectomy is an effective surgical treatment for multiple bilobar liver metastases from colon cancer;however,one of the primary obstacles to completing surgical resection for these cases is an insufficient volume of the future remnant liver,which may cause postoperative liver failure.To induce atrophy of the unilateral lobe and hypertrophy of the future remnant liver,procedures to occlude the portal vein have been conventionally used prior to major hepatectomy.We report a case of a 50-year-old woman in whom two-stage hepatectomy was performed in combination with intraoperative ligation of the portal vein and the bile duct of the right hepatic lobe.This procedure was designed to promote the atrophic effect on the right hepatic lobe more effectively than the conventional technique,and to the best of our knowledge,it was used for the first time in the present case.Despite successful induction of liver volume shift as well as the following procedure,the patient died of subsequent liver failure after developing recurrent tumors.We discuss the first case in which simultaneous ligation of the portal vein and the biliary system was successfully applied as part of the first step of two-stage hepatectomy.展开更多
Background and Aims:Hepatopulmonary syndrome(HPS)is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease.To date,liver transplantation remains the only effective treatment ...Background and Aims:Hepatopulmonary syndrome(HPS)is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease.To date,liver transplantation remains the only effective treatment for HPS.This study aimed to explore the preventative role of baicalein in HPS development.Methods:Sixty male rats were randomly assigned to three groups:sham,common bile duct ligation(CBDL),and baicalein,receiving intraperitoneal injections of baicalein(40 mg·kg^(-1)·d^(-1),diluted in saline)for 21 days.Survival rate,liver and kidney function,and bile acid metabolism levels were evaluated.Liver and lung angiogenesis and hepatic glycogen staining were assessed,and the expression of relevant proteins was evaluated by immunohistochemistry.Results:Baicalein improved survival rates and hypoxemia in rats post-CBDL,reducing angiogenic protein levels and enhancing glucose homeostasis.Compared to the untreated group,baicalein suppressed the expression of vascular endothelial growth factor,placental growth factors,matrix metalloprotease 9 and C-X-C motif chemokine 2,and it increased the expression of glycemic regulatory proteins,including dipeptidyl peptidase-4,sirtuin 1,peroxisome proliferatoractivated receptor gamma co-activator 1α,and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3.Conclusion:Baicalein significantly improves hepatic function and hypoxia in HPS rats by attenuating pathological angiogenesis in the liver and lungs,showing promise as a treatment for HPS.展开更多
Objective Compared to portal vein ligation(PVL),simultaneous bile duct and portal vein ligation(BPL)can significantly enhance hypertrophy of the intact liver.This study aimed to investigate whether BPL could improve s...Objective Compared to portal vein ligation(PVL),simultaneous bile duct and portal vein ligation(BPL)can significantly enhance hypertrophy of the intact liver.This study aimed to investigate whether BPL could improve survival after extended hepatectomy independently of an increased remnant liver.Methods We adopted rat models of 90%BPL or 90%PVL.To investigate the role of bile acids(BAs)the BA pools in the PVL and BPL groups were altered by the diet.Staged resection preserving 10%of the estimated liver weight was performed 3 days after BPL;PVL;or sham operation.Histology,canalicular network(CN)continuity;and hepatocyte polarity were evaluated.Results At 3 days after BPL;PVL;or sham operation when the volumetric difference of the intended liver remained insignificant,the survival rates after extended hepatectomy were 86.7%,47%,and 23.3%,respectively(P<0.01).BPL induced faster restoration of canalicular integrity along with an intensive but transient BA overload.Staged hepatectomy after BPL shortened the duration of the bile CN disturbance and limited BA retention.Decreasing the BA pools in the rats that underwent BPL could compromise these effects,whereas increasing the BA pools of rats that underwent PVL could induce similar effects.The changes in CN restoration were associated with activation of LKB1.Conclusion In addition to increasing the future remnant liver,BPL shortened the duration of the spatial disturbance of the CN and could significantly improve the tolerance of the hypertrophied liver to staged resection.BPL may be a safe and efficient future option for patients with an insufficient remnant liver.展开更多
Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the r...Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.展开更多
AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology. METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation...AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology. METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk). To determine renal function parameters, rats wereplaced in metabolic cages and, at the end of the experiment, blood and urine samples were obtained. Histology and hydroxyproline content were analyzed in liver and renal tissue. RESULTS: Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P = 0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including signif icant increase in serum creatinine and reductions in creatinine clearance, water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic f ibrosis according to post-procedure time was confirmed by histology. The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue. CONCLUSION: Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.展开更多
AIM： TO assess the effect of iron reduction after phlebotomy in rats with ＂normal＂ hepatic iron concentration （HIC） on the progression of hepatic fibrosis, as a result of bile duct ligation （BDL）. METHODS： Rat...AIM： TO assess the effect of iron reduction after phlebotomy in rats with ＂normal＂ hepatic iron concentration （HIC） on the progression of hepatic fibrosis, as a result of bile duct ligation （BDL）. METHODS： Rats underwent phlebotomy before or after sham operation or BDL. Animals undergone only BDL or sham operation served as controls. Two weeks after surgery, indices of hepatic damage and fibrosis were evaluated. RESULTS： Phlebotomy lowered HIC. Phlebotomy after BDL was associated with body weight increase, lower hepatic weight, less portal hypertension, less periportal necrosis, less portal inflammation, lower hepatic activity index score and higher albumin levels. On the other hand, phlebotomy before BDL was associated with body weight decrease and hepatic activity index score increase. Phlebotomy after sham operation was not associated with any hepatic or systemic adverse effects. CONCLUSION： Reduction of HIC after induction of liver damage may have beneficial effects in BDL rats. However, iron deficiency could induce impairment of liver function and may make the liver more susceptible to insults like BDL.展开更多
A 58 years old male patient underwent esophagectomy for esophageal cancer.Refractory chylothorax happened after operation in spite of different treatment including conservation therapy and thoracic duct ligation.He wa...A 58 years old male patient underwent esophagectomy for esophageal cancer.Refractory chylothorax happened after operation in spite of different treatment including conservation therapy and thoracic duct ligation.He was enterally administrated 250 mL 30% intralipid before operation.Exploration showed there was a milky leakage from the soft tissue near the anastomotic stoma behind aortic arch where is difficult to handle.We gently mobilized the aorta in the front of the ninth spine and bundled it with its adjacent tissue including azygos vein and thoracic duct with a dacron patch.The leakage ceased rightly and the following recovery went smoothly.展开更多
Cholestasis results in a buildup of bile acids in serum and in hepatocytes.Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acidinduced apoptosis as the major cause of hepatocellu...Cholestasis results in a buildup of bile acids in serum and in hepatocytes.Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acidinduced apoptosis as the major cause of hepatocellular injury.Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology.Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum,liver,and bile to very low levels of detection.Interestingly,toxic bile acid levels are seemingly far lower than previously hypothesized.The initial hypothesis has been based largely upon the exposure of μmol/L concentrations of toxic bile acids and bile salts to primary hepatocytes in cell culture,the possibility that in vivo bile acid concentrations may be far lower than the observed in vitro toxicity has far reaching implications in the mechanism of injury.This review will focus on both how different bile acids and different bile acid concentrations can affect hepatocytes during cholestasis,and additionally provide insight into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis,but may involve largely inflammatory cell-mediated liver cell necrosis.展开更多
AIM: To investigate the role of heme oxygenase-1 (HO-1) in pathogenesis of experimental hepatorenal syndrome (HRS). METHODS: Rats were divided into liver cirrhotic group, zinc protoporphyrin IX (ZnPP) treatment group,...AIM: To investigate the role of heme oxygenase-1 (HO-1) in pathogenesis of experimental hepatorenal syndrome (HRS). METHODS: Rats were divided into liver cirrhotic group, zinc protoporphyrin IX (ZnPP) treatment group, cobalt protoporphyrin (CoPP) treatment group and sham group. Biliary cirrhosis was established by bile duct ligation in the first three groups. Rats in the ZnPP and CoPP treatment groups received intraperitoneal injection of ZnPP and CoPP, respectively, 24 h before sample collection. Expression of HO-1 mRNA in kidney was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohis-tochemical analysis. Hematoxylin and eosin staining was performed to observe liver cirrhosis and renal structure. Renal artery blood flow, mean arterial pressure and portal vein pressure, 24 h total urinary volume, serum and urine sodium concentrations, and creatinine clearance rate (Ccr) were also measured.RESULTS: The HO-1 mRNA and protein expression levels in kidney, 24 h total urinary volume, renal artery blood flow, serum and urine sodium concentration and Ccr were lower in cirrhotic group than in sham group (P < 0.05). However, they were significantly lower in ZnPP treatment group than in cirrhotic group and significantly higher in CoPP treatment group than in cirrhotic group (P < 0.05). CONCLUSION: Low HO-1 expression level in kidney is an important factor for experimental HRS.展开更多
Xerostomia is a severe side effect of radiation therapy in head and neck cancer patients. To date, no satisfactory treatment option has been established. Because mesenchymal stem cells（MSCs） have been identified as ...Xerostomia is a severe side effect of radiation therapy in head and neck cancer patients. To date, no satisfactory treatment option has been established. Because mesenchymal stem cells（MSCs） have been identified as a potential treatment modality, we aimed to evaluate stem cell distribution following intravenous and intraglandular injections using a surgical model of salivary gland damage and to analyse the effects of MSC injections on the recruitment of immune cells. The submandibular gland ducts of rats were surgically ligated. Syngeneic adult MSCs were isolated, immortalised by simian virus 40（SV40） large T antigen and characterized by flow cytometry. MSCs were injected intravenously and intraglandularly. After 1, 3 and 7 days, the organs of interest were analysed for stem cell recruitment. Inflammation was analysed by immunohistochemical staining. We were able to demonstrate that, after intravenous injection, MSCs were recruited to normal and damaged submandibular glands on days 1, 3 and 7. Unexpectedly, stem cells were recruited to ligated and non-ligated glands in a comparable manner. After intraglandular injection of MSCs into ligated glands, the presence of MSCs, leucocytes and macrophages was enhanced, compared to intravenous injection of stem cells. Our data suggest that injected MSCs were retained within the inflamed glands, could become activated and subsequently recruited leucocytes to the sites of tissue damage.展开更多
BACKGROUND Cirrhosis is an important health problem characterized by a significant change in liver parenchyma.In animals,this can be reproduced by an experimental model of bile duct ligation(BDL).Melatonin(MLT)is a ph...BACKGROUND Cirrhosis is an important health problem characterized by a significant change in liver parenchyma.In animals,this can be reproduced by an experimental model of bile duct ligation(BDL).Melatonin(MLT)is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties,including its antioxidant potential.AIM To evaluate MLT’s effects on oxidative stress,the inflammatory process,and DNA damage in an experimental model of secondary biliary cirrhosis.METHODS Male Wistar rats were divided into 4 groups:Control(CO),CO+MLT,BDL,and BDL+MLT.MLT was administered(20 mg/kg)daily beginning on day 15 after biliary obstruction.On day 29 the animals were killed.Blood samples,liver tissue,and bone marrow were collected for further analysis.RESULTS BDL caused changes in biochemical and histological parameters and markers of inflammatory process.Thiobarbituric acid(0.46±0.01)reactive substance levels,superoxide dismutase activity(2.30±0.07)and nitric oxide levels(2.48±0.36)were significantly lower(P<0.001)n the groups that received MLT.DNA damage was also lower(P<0.001)in MLT-treated groups(171.6±32.9)than the BDL-only group(295.5±34.8).Tissue damage and the expression of nuclear factor kappa B,interleukin-1β,Nrf2,NQO1 and Hsp70 were significantly lower in animals treated with MLT(P<0.001).CONCLUSION When administered to rats with BDL-induced secondary biliary cirrhosis,MLT effectively restored the evaluated parameters.展开更多
基金Supported by the Chang Gung Memorial Hospital, Taoyuan, Taiwan, China, CMRPG 33014, CMRPG 33063 and CMRP 800
文摘AIM： To build up the research models of hepatic fibrosis in mice.METHODS： Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate （ANIT）, allyl alcohol （AA）,carbon tetrachloride （CCl4）, 3,5-diethoxycarbonyl-l,4-dihydrocollidine （DDC）, and silica, or subjected to common bile duct ligation （CBDL） to induce hepatic injury. Liver biopsies were performed every 4 wk to evaluate hepatic fibrosis over a period of 6 mo. Cumulative cirrhosis and survival curves were constructed by life table method and compared with Wilcoxon test.RESULTS： Under the dosages used, there was neither mortality nor cirrhosis in AA and silica-treated groups. DDC and ANIT caused cirrhosis within 4-12 and 12-24 wk, respectively.Both showed significantly faster cirrhosis induction at high dosages without significant alteration of survival. The duration for cirrhosis induction by CCl4 ranged from 4 to 20 wk, mainly dependent upon the dosage. However, the increase in CCl4 dosage significantly worsened survival. Intraperitoneal CCl4 administration resulted in better survival in comparison with garage administration at high dosage, but not at medium and low dosages. After CBDL, all the mice developed liver cirrhosis within 4-8 wk and then died by the end of 26 wk.CONCLUSION： CBDL and administrations of ANIT, CCl4, and DDC ensured liver cirrhosis. CBDL required the least amount of time in cirrhosis induction, but caused shortened lives of mice. It was followed by DDC and ANIT administration with favorable survival. As for CCl4, the speed of cirrhosis induction and the mouse survival depended upon the dosages and the administration route.
文摘Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Methods Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. Results There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Conclusion Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis.
基金grants from the National Institute of Health and by a grant from the Deutsche Forschungsgemeinschaft, No. FR 1644/4-1
文摘AIM： To investigate the effects of heme oxygenase-1 （HO-1） against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either cobalt protoporphyrin （CoPP）, a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and q/tokine and collagen- Iα （Col- I α） mRNA expression was detected using RNase protection assays.RESULTS： Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius redpositive areas were increased to about 11.7% after BDL. Collagen-1 α and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression.CONCLUSION： Hepatic fibrosis due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1 overexpression increases liver injury in rats under conditions of experimental chronic cholestasis.
基金supported by‘Cooperative Research Program for Agriculture Science&Technology Development’(No.PJ01132001)funded by Rural Development Administration,Republic of Korea
文摘Objective:To evaluate the possible protective effect of Citrus aurantium peel extract(CAE)against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice.Methods:Male ICR mice were divided to 5 groups:1)Control group(Sham-operated mice),2)Cholestatic liver injury group induced by bile duct ligation(BDL),3)BDL mice treated with silymarin(200 mg/kg)for 4 weeks,4)BDL mice treated with 50 mg/kg CAE for 4 weeks,5)BDL mice treated with 200 mg/kg CAE for 4 weeks.Mice were sacrificed and liver fibrosis was evaluated by serum and hepatic tissue biochemistry tests and liver histopathological examination.Effects of CAE on inflammation and apoptosis gene regulation were investigated through real-time PCR.CAE effect on lipid metabolism related signaling was determined by western blot analysis.Results:In BDL mice,administration of CAE for 4 weeks markedly attenuated liver fibrosis based on histopathological alteration.Serum and hepatic tissue biochemistry results revealed that CAE(50 and 200 mg/kg)decreased the levels of alanine transaminase,aspartate transaminase,gamma glutamyl transferase,total bilirubin,nitric oxide,and thiobarbituric acid reactive substances.Real-time PCR and western blot analysis showed that CAE regulated inflammation,apoptosis,and lipid metabolism factors increased by BDL.Interleukin family,tumor necrosis factorα,and related apoptosis factors m RNA levels were increased by BDL treatment.However,these increases were suppressed by CAE administration.In addition,CAE effectively increased phosphorylation of AMPactivated protein kinase,nuclear factor E2-related factor 2,and related cytoprotective proteins.Conclusions:CAE can efficiently regulate BDL-induced liver injury with antioxidant,antiinflammatory,and antiapoptotic activities.
文摘The epididymis is divided into caput, corpus and cauda regions, organized into intraregional segments separated by connective tissue septa （CTS）. In the adult rat and mouse these segments are highly differentiated. Regulation of these segments is by endocrine, lumicrine and paracrine factors, the relative importance of which remains under investigation. Here, the ability of the CTS to limit signaling in the interstitial compartment is reviewed as is the effect of 15 days of unilateral efferent duct ligation （EDL） on ipsilateral segmental transcriptional profiles. Inter-segmental microperifusions of epidermal growth factor （EGF）, vascular endothelial growth factor （VEGFA） and fibroblast growth factor 2 （FGF2） increased phosphorylation of mitogen activated protein kinase （MAPK） in segments 1 and 2 of the rat epididymis and the effects of all factors were limited by the CTS separating the segments. Microan＇ay analysis of segmental gene expression determined the effect of 15 days of unilateral EDL on the transcriptome-wide gene expression of rat segments 1-4. Over 11 000 genes were expressed in each of the four segments and over 2 000 transcripts in segment 1 responded to deprivation of testicular lumicrine factors. Segments 1 and 2 of control tissues were the most transcriptionally different and EDL had its greatest effects there. In the absence of lumicrine factors, all four segments regressed to a transcriptionally undifferentiated state, consistent with the less differentiated histology. Deprivation of lumicrine factors could stimulate an individual gene＇s expression in some segments yet suppress it in others. Such results reveal a higher complexity of the regulation of rat epididymal segments than that is generally appreciated. （Asian J Androl 2007 July; 9： 565-573）
文摘AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. METHODS: A total of 40 male Sprague-Dawley rats, weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 10) rats underwent laparotomy alone and the bile duct was just dissected from the surrounding tissue. Group 2 rats (untreated, n = 10) were subjected to bile duct ligation (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats (high-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. At the end of the two-week period, biochemical and histological evaluations were processed. RESULTS: The mean serum bilirubin and liver enzyme levels signifi cantly decreased, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) values were significantly increased in low-dose dexa and high-dose dexa groups when compared to the untreated group. The histopathological score was significantly less in the low-dose and high-dose dexa groups compared to the untreated rats. In the low-dose dexa group, moderate liver damage was seen, while mild liver damage was observed in the high-dose dexa group. CONCLUSION: Corticosteroids reduced liver damage produced by bile duct obstruction. However, the histopathological score was not signifi cantly lower in the high-dose corticosteroid group as compared to the low-dose group. Thus, low-dose corticosteroid provides asignifi cant reduction of liver damage without increased side effects, while high dose is associated not with lower fi brosis but with increased side effects.
基金Grants from the National Institute of Alcohol Abuse and Alcoholism (NIAAA)by a grant from the Deutsche Forschungsgemeinschaft,No.FR 1644/4-1
文摘AIM： To investigate the effects of （dietary） glycine against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawley （SD） rats. Three days later, BDL or sham-operation was performed. Rats were sacrificed 1 to 3 d after BDL. The influence of deoxycholic acid （DCA） in the presence or absence of glycine on liver cells was determined by measurement of calcium and chloride influx in cultivated Kupffer cells and lactate dehydrogenase （LDH） activity was determined in the supernatant of cultivated hepatocytes.RESULTS： Serum alanine transaminase levels increased to about 600 U/L 1 d alter BDL. However, enzyme release was blunted by about two third in rats receiving glycine. Release of the alkaline phosphatase and aspartate aminotransferase was also blocked significantly in the group fed glycine. Focal necrosis was observed 2 d after BDL. Glycine partially blocked the histopathological changes. Incubation of Kupffer cells with DCA led to increased intracellular calcium that could be blocked by incubation with glycine. However, systemic blockage of Kupffer cells with gadolinium chloride had no effects on transaminase release. Incubation of isolated hepatocytes with DCA led to a significant release of LDH after 4 h. This release was largely blocked when incubation with glycine was performed.CONCLUSION： These data indicate that glycine significantly decreased liver injury, most likely by a direct effect on hepatocytes. Kupffer cells do not appear to play an important role in the pathological changes caused by cholestasis.
基金the Natural Science Foundation of Hunan Province,No.2019JJ40444(to Xiao EH)and 2021JJ30945(to Luo YH).
文摘BACKGROUND Bile duct ligation(BDL)in animals is a classical method for mimicking cholestatic fibrosis.Although different surgical techniques have been described in rats and rabbits,mouse models can be more cost-effective and reproducible for investigating cholestatic fibrosis.Magnetic resonance imaging(MRI)has made great advances for noninvasive assessment of liver fibrosis.More comprehensive liver fibrotic features of BDL on MRI are important.However,the utility of multiparameter MRI to detect liver fibrosis in a BDL mouse model has not been assessed.AIM To evaluate the correlation between the pathological changes and multiparameter MRI characteristics of liver fibrosis in a BDL mouse model.METHODS Twenty-eight healthy adult male balb/c mice were randomly divided into four groups:sham,week 2 BDL,week 4 BDL,and week 6 BDL.Multiparameter MRI sequences,included magnetic resonance cholangiopancreatography,T1-weighted,T2-weighted,T2 mapping,and pre-and post-enhanced T1 mapping,were performed after sham and BDL surgery.Peripheral blood and liver tissue were collected after MRI.For statistical analysis,Student’s t-test and Pearson’s correlation coefficient were used.RESULTS Four mice died after BDL surgery;seven,six,five and six mice were included separately from the four groups.Signal intensities of liver parenchyma showed no difference on TI-and T2-weighted images.Bile duct volume,ΔT1 value,T2 value,and the rate of liver fibrosis increased steadily in week 2 BDL,week 4 BDL and week 6 BDL groups compared with those in the sham group(P<0.01).Alanine aminotransferase and aspartate transaminase levels initially surged after surgery,followed by a gradual decline over time.Strong correlations were found between bile duct volume(r=0.84),T2 value(r=0.78),ΔT1 value(r=0.62),and hepatic fibrosis rate(all P<0.01)in the BDL groups.CONCLUSION The BDL mouse model induces changes that can be observed on MRI.The MRI parameters correlate with the hepatic fibrosis rate and allow for detection of cholestatic fibrosis.
基金supported by the National Natural Science Foundation of China(Nos.82173884,81872930,82073922 and 81872833)the“Double First-Class”university project(No.CPU2018GY22,China)。
文摘Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal Oct expressions using bile duct ligation(BDL)rats.Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure,associated with decreased intestinal absorption and increased urinary excretion.Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2.In vitro cell experiments show that chenodeoxycholic acid(CDCA),bilirubin and farnesoid X receptor(FXR)agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1,which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR.Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL,which are confirmed using CDCA-treated and bilirubin-treated rats.A disease-based physiologically based pharmacokinetic model characterizing intestinal,hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats.In conclusion,BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats,finally,decreasing plasma exposure and impairing hypoglycemic effects of metformin.BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.
文摘Hepatectomy is an effective surgical treatment for multiple bilobar liver metastases from colon cancer;however,one of the primary obstacles to completing surgical resection for these cases is an insufficient volume of the future remnant liver,which may cause postoperative liver failure.To induce atrophy of the unilateral lobe and hypertrophy of the future remnant liver,procedures to occlude the portal vein have been conventionally used prior to major hepatectomy.We report a case of a 50-year-old woman in whom two-stage hepatectomy was performed in combination with intraoperative ligation of the portal vein and the bile duct of the right hepatic lobe.This procedure was designed to promote the atrophic effect on the right hepatic lobe more effectively than the conventional technique,and to the best of our knowledge,it was used for the first time in the present case.Despite successful induction of liver volume shift as well as the following procedure,the patient died of subsequent liver failure after developing recurrent tumors.We discuss the first case in which simultaneous ligation of the portal vein and the biliary system was successfully applied as part of the first step of two-stage hepatectomy.
基金supported by the National Science Foundation of China(No.82070630 to BY,No.82100658 to YL)Science Foundation of Chongqing(cstc2019jcyj-msxmX0667 to ZZ)National Key R&D Program of China(No.2018YFC0116702 to BY).
文摘Background and Aims:Hepatopulmonary syndrome(HPS)is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease.To date,liver transplantation remains the only effective treatment for HPS.This study aimed to explore the preventative role of baicalein in HPS development.Methods:Sixty male rats were randomly assigned to three groups:sham,common bile duct ligation(CBDL),and baicalein,receiving intraperitoneal injections of baicalein(40 mg·kg^(-1)·d^(-1),diluted in saline)for 21 days.Survival rate,liver and kidney function,and bile acid metabolism levels were evaluated.Liver and lung angiogenesis and hepatic glycogen staining were assessed,and the expression of relevant proteins was evaluated by immunohistochemistry.Results:Baicalein improved survival rates and hypoxemia in rats post-CBDL,reducing angiogenic protein levels and enhancing glucose homeostasis.Compared to the untreated group,baicalein suppressed the expression of vascular endothelial growth factor,placental growth factors,matrix metalloprotease 9 and C-X-C motif chemokine 2,and it increased the expression of glycemic regulatory proteins,including dipeptidyl peptidase-4,sirtuin 1,peroxisome proliferatoractivated receptor gamma co-activator 1α,and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3.Conclusion:Baicalein significantly improves hepatic function and hypoxia in HPS rats by attenuating pathological angiogenesis in the liver and lungs,showing promise as a treatment for HPS.
基金supported by the Natural Science Foundation of Beijing Municipality(No.7194317).
文摘Objective Compared to portal vein ligation(PVL),simultaneous bile duct and portal vein ligation(BPL)can significantly enhance hypertrophy of the intact liver.This study aimed to investigate whether BPL could improve survival after extended hepatectomy independently of an increased remnant liver.Methods We adopted rat models of 90%BPL or 90%PVL.To investigate the role of bile acids(BAs)the BA pools in the PVL and BPL groups were altered by the diet.Staged resection preserving 10%of the estimated liver weight was performed 3 days after BPL;PVL;or sham operation.Histology,canalicular network(CN)continuity;and hepatocyte polarity were evaluated.Results At 3 days after BPL;PVL;or sham operation when the volumetric difference of the intended liver remained insignificant,the survival rates after extended hepatectomy were 86.7%,47%,and 23.3%,respectively(P<0.01).BPL induced faster restoration of canalicular integrity along with an intensive but transient BA overload.Staged hepatectomy after BPL shortened the duration of the bile CN disturbance and limited BA retention.Decreasing the BA pools in the rats that underwent BPL could compromise these effects,whereas increasing the BA pools of rats that underwent PVL could induce similar effects.The changes in CN restoration were associated with activation of LKB1.Conclusion In addition to increasing the future remnant liver,BPL shortened the duration of the spatial disturbance of the CN and could significantly improve the tolerance of the hypertrophied liver to staged resection.BPL may be a safe and efficient future option for patients with an insufficient remnant liver.
基金supported by grants from the National Natural Science Foundation of China(No.81102692)the Natural Science Foundation of Hubei Province,China(No.JX6B09)the Fundamental Research Funds for the Central Universities,China(No.2015QN203)
文摘Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.
基金FAPEMIG (Funda■o de Amparo à Pesquisa do Estado de Minas Gerais)CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico)PRONEX (Grupos de Excelência)
文摘AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology. METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk). To determine renal function parameters, rats wereplaced in metabolic cages and, at the end of the experiment, blood and urine samples were obtained. Histology and hydroxyproline content were analyzed in liver and renal tissue. RESULTS: Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P = 0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including signif icant increase in serum creatinine and reductions in creatinine clearance, water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic f ibrosis according to post-procedure time was confirmed by histology. The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue. CONCLUSION: Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.
文摘AIM： TO assess the effect of iron reduction after phlebotomy in rats with ＂normal＂ hepatic iron concentration （HIC） on the progression of hepatic fibrosis, as a result of bile duct ligation （BDL）. METHODS： Rats underwent phlebotomy before or after sham operation or BDL. Animals undergone only BDL or sham operation served as controls. Two weeks after surgery, indices of hepatic damage and fibrosis were evaluated. RESULTS： Phlebotomy lowered HIC. Phlebotomy after BDL was associated with body weight increase, lower hepatic weight, less portal hypertension, less periportal necrosis, less portal inflammation, lower hepatic activity index score and higher albumin levels. On the other hand, phlebotomy before BDL was associated with body weight decrease and hepatic activity index score increase. Phlebotomy after sham operation was not associated with any hepatic or systemic adverse effects. CONCLUSION： Reduction of HIC after induction of liver damage may have beneficial effects in BDL rats. However, iron deficiency could induce impairment of liver function and may make the liver more susceptible to insults like BDL.
文摘A 58 years old male patient underwent esophagectomy for esophageal cancer.Refractory chylothorax happened after operation in spite of different treatment including conservation therapy and thoracic duct ligation.He was enterally administrated 250 mL 30% intralipid before operation.Exploration showed there was a milky leakage from the soft tissue near the anastomotic stoma behind aortic arch where is difficult to handle.We gently mobilized the aorta in the front of the ninth spine and bundled it with its adjacent tissue including azygos vein and thoracic duct with a dacron patch.The leakage ceased rightly and the following recovery went smoothly.
基金Supported by The National Institutes of Health grants,R01 DK070195 and R01 AA12916,to Jaeschke Hthe "Training Program in Environmental Toxicology",T32 ES007079-26A2 from the National Institute of Environmental Health Sciences
文摘Cholestasis results in a buildup of bile acids in serum and in hepatocytes.Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acidinduced apoptosis as the major cause of hepatocellular injury.Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology.Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum,liver,and bile to very low levels of detection.Interestingly,toxic bile acid levels are seemingly far lower than previously hypothesized.The initial hypothesis has been based largely upon the exposure of μmol/L concentrations of toxic bile acids and bile salts to primary hepatocytes in cell culture,the possibility that in vivo bile acid concentrations may be far lower than the observed in vitro toxicity has far reaching implications in the mechanism of injury.This review will focus on both how different bile acids and different bile acid concentrations can affect hepatocytes during cholestasis,and additionally provide insight into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis,but may involve largely inflammatory cell-mediated liver cell necrosis.
基金Supported by National Natural Science Foundation of China, No. 30970886Science and Technology Project of Dalian,No. 2008E13SF193
文摘AIM: To investigate the role of heme oxygenase-1 (HO-1) in pathogenesis of experimental hepatorenal syndrome (HRS). METHODS: Rats were divided into liver cirrhotic group, zinc protoporphyrin IX (ZnPP) treatment group, cobalt protoporphyrin (CoPP) treatment group and sham group. Biliary cirrhosis was established by bile duct ligation in the first three groups. Rats in the ZnPP and CoPP treatment groups received intraperitoneal injection of ZnPP and CoPP, respectively, 24 h before sample collection. Expression of HO-1 mRNA in kidney was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohis-tochemical analysis. Hematoxylin and eosin staining was performed to observe liver cirrhosis and renal structure. Renal artery blood flow, mean arterial pressure and portal vein pressure, 24 h total urinary volume, serum and urine sodium concentrations, and creatinine clearance rate (Ccr) were also measured.RESULTS: The HO-1 mRNA and protein expression levels in kidney, 24 h total urinary volume, renal artery blood flow, serum and urine sodium concentration and Ccr were lower in cirrhotic group than in sham group (P < 0.05). However, they were significantly lower in ZnPP treatment group than in cirrhotic group and significantly higher in CoPP treatment group than in cirrhotic group (P < 0.05). CONCLUSION: Low HO-1 expression level in kidney is an important factor for experimental HRS.
基金supported by the Novartis Foundation for Therapeutic Research
文摘Xerostomia is a severe side effect of radiation therapy in head and neck cancer patients. To date, no satisfactory treatment option has been established. Because mesenchymal stem cells（MSCs） have been identified as a potential treatment modality, we aimed to evaluate stem cell distribution following intravenous and intraglandular injections using a surgical model of salivary gland damage and to analyse the effects of MSC injections on the recruitment of immune cells. The submandibular gland ducts of rats were surgically ligated. Syngeneic adult MSCs were isolated, immortalised by simian virus 40（SV40） large T antigen and characterized by flow cytometry. MSCs were injected intravenously and intraglandularly. After 1, 3 and 7 days, the organs of interest were analysed for stem cell recruitment. Inflammation was analysed by immunohistochemical staining. We were able to demonstrate that, after intravenous injection, MSCs were recruited to normal and damaged submandibular glands on days 1, 3 and 7. Unexpectedly, stem cells were recruited to ligated and non-ligated glands in a comparable manner. After intraglandular injection of MSCs into ligated glands, the presence of MSCs, leucocytes and macrophages was enhanced, compared to intravenous injection of stem cells. Our data suggest that injected MSCs were retained within the inflamed glands, could become activated and subsequently recruited leucocytes to the sites of tissue damage.
基金Supported by Fundo de IncentivoàPesquisa e Eventos(FIPE).
文摘BACKGROUND Cirrhosis is an important health problem characterized by a significant change in liver parenchyma.In animals,this can be reproduced by an experimental model of bile duct ligation(BDL).Melatonin(MLT)is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties,including its antioxidant potential.AIM To evaluate MLT’s effects on oxidative stress,the inflammatory process,and DNA damage in an experimental model of secondary biliary cirrhosis.METHODS Male Wistar rats were divided into 4 groups:Control(CO),CO+MLT,BDL,and BDL+MLT.MLT was administered(20 mg/kg)daily beginning on day 15 after biliary obstruction.On day 29 the animals were killed.Blood samples,liver tissue,and bone marrow were collected for further analysis.RESULTS BDL caused changes in biochemical and histological parameters and markers of inflammatory process.Thiobarbituric acid(0.46±0.01)reactive substance levels,superoxide dismutase activity(2.30±0.07)and nitric oxide levels(2.48±0.36)were significantly lower(P<0.001)n the groups that received MLT.DNA damage was also lower(P<0.001)in MLT-treated groups(171.6±32.9)than the BDL-only group(295.5±34.8).Tissue damage and the expression of nuclear factor kappa B,interleukin-1β,Nrf2,NQO1 and Hsp70 were significantly lower in animals treated with MLT(P<0.001).CONCLUSION When administered to rats with BDL-induced secondary biliary cirrhosis,MLT effectively restored the evaluated parameters.
