Stroke is a leading cause of death worldwide. Up to one thousand potential drugs or interventions have been developed to treat stroke, out of which;60 have gone on to clinical trials. However, none of them has been su...Stroke is a leading cause of death worldwide. Up to one thousand potential drugs or interventions have been developed to treat stroke, out of which;60 have gone on to clinical trials. However, none of them has been successful. New insights into the molecular and cellular mechanisms of ischemia-induced injury are needed for discovering new therapeutic targets. Recently, Drosophila has been used to uncover new hypoxia-related genes. In this study, we describe an efficient and reliable assay with a sophisticated apparatus for studying the effects of oxygen deprivation on flies. Using this assay, wild-type flies were exposed to an anoxic environment for varying lengths of time, then the cumulative death rate and mobility recovery were systematically analyzed. We found that anoxia for over one hour caused lethality. The cumulative death rate on day 5 after anoxia was linearly and positively correlatedwith the duration of anoxia, and reached 50% when the duration was 2.5 h–3 h. We also found that the mobility recovery in normoxia was slow, as the climbing ability remained largely unchanged 4 h–6 h after 2.5-h of anoxia.We suggest that 2.5 h–3 h of anoxia and 4 h–6 h of recovery before mobility analysis are appropriate for future use of the anoxia assay.展开更多
AIM: To investigate the protective effect of isoflurane on energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation, and to compare isoflurane with halothane. METHODS: Hepatocytes freshly isolated f...AIM: To investigate the protective effect of isoflurane on energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation, and to compare isoflurane with halothane. METHODS: Hepatocytes freshly isolated from fed rats were suspended in Krebs-Henseleit buffer, and incubated in sealed flasks under O2/CO2 or N2/CO2 (95%/5%, V/V) for 30 or 60 min, followed by 5 or 10 min of reoxygenation, with an added volatile anesthetic or not. ATP, ADP, and adenosine monophosphate in hepatocytes were determined by high performance liquid chromatography, and energy charge was calculated. RESULTS: During 30 min of anoxia, the energy charge and total adenine nudeotide steadily increased with the isoflurane dose from 0 to 2 minimum alveolar anesthetic concentration (MAC), then decreased from 2 to 3 MAC. In short incubations (30-35 min) at 1 MAC isoflurane, energy charge modestly decreased during anoxia, which was partially prevented by isoflurane and completely reversed by reoxygenation, and total adenine nudeotide did not decrease. In long incubations (60-70 min), both energy charge and total adenine nudeotide greatly decreased during anoxia, with partial and no reversal by reoxygenation, respectively. Isoflurane partly prevented decreases in both energy charge and total adenine nudeotide during anoxia and reoxygenation. In addition, 1 MAC isoflurane obviously increased ATP/ADP, which could not be changed by 1 MAC halothane. CONCLUSION: Isoflurane partially protects isolated hepatocytes against decreases in both energy charge and total adenine nudeotide during short (reversible) or long (irreversible) anoxia.展开更多
Objective:To explore the effect of emulsified isoflurane(EI)on apoptosis of anoxia-reoxygenation neonatal rat cardiomyocytea and relevant protein expression.Methods:Cardiac muscle anoxiareoxygenation damage model was ...Objective:To explore the effect of emulsified isoflurane(EI)on apoptosis of anoxia-reoxygenation neonatal rat cardiomyocytea and relevant protein expression.Methods:Cardiac muscle anoxiareoxygenation damage model was established with culture in vitro neonatal rat cardiomyocytes.The cardiomyocytes were divided into control group,model group,fat emulsion group and EI group.The cardiomyocytes apoptosis rates and lactic dehydrogenase(LDH),superoxide dismutase(SOD)and malondialdehyde(MDA)index standardization were detected after relevant treatment The expression of apoptosis-related proteins Bel-2,Bax and Caspase-3 were detected with Western blot approach.Results:After hypoxia/reoxygenation(H/R)model was treated by EI,the cells apoptosis rate decreased and was dramatically below the fat emulsion group(P<0.05),Cardiomyocytes biochemical index detection presented that,compared with the control group that the LDH activity and MDA content dramatically increased(P<0.05),while the SOD activity notably decreased(P<0.05);compared with the H/R group,the SOD activity of the fat emulsion group and EI group increased(P<0.05);while the LDH activity and MDA content decreased(P<0.05).And the change of the EI group was more remarkable than the fat emulsion group(P<0.05).The Western blot analysis presented that,compared with the control group,the Bcl-2 protein expression of the other groups significantly decreased(P<0.05),the expressions of Bax protein and Caspase-3protein increased significantly(P<0.05);compared with H/R group,cardiomyocytes Bc1-2protein expression of EI group increased significantly(P<0.05),the expressions of Bax protein and Caspase-3 protein decreased significantly(P<0.05),and the change of EI group was more remarkable than the fat emulsion group(P<0.05).Conclusions:EI can inhabit the apoptosis of anoxia-reoxygenation damage model cardiomyocytes,and may he related to the up-regulation of expression of Bcl-2 and down-regulation of expression of Caspase-3 protein.展开更多
The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation（A/R） injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathwa...The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation（A/R） injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathway. We employed simulated A/R of neonatal rat ventricular myocytes（NRVM） as an in vitro model of ischemial/reperfusion（I/R） injury to the heart. NRVM were pretreated with four different concentrations of Rapamycin（20, 50, 100, 150 μmol/L）, and pretreated with 10 mmol/L 3-methyladenine（3MA） for inhibiting autophagy during A/R. Then, Western blot analysis was used to examine variation in the expression of LC3-Ⅱ, LC3-Ⅰ, Bim, caspase-3, p-PI3KⅠ, PI3KⅠ, p-Akt and Akt. In our model, Rapamycin had a preferential action on autophagy, increasing the expression of LC3-Ⅱ/ LC3-Ⅰ, whereas decreasing the expression of Bim and caspase-3. Moreover, our results also demonstrated that Rapamycin inhibited the activation of p-PI3KⅠ and enhanced the activation of p-Akt. It is concluded that Rapamycin has a cardioprotection effect by inducing autophagy in a concentration-dependent manner against apopotosis through PI3K/Akt signaling pathway during A/R in NRVM.展开更多
Objective： To study protective effect of insulin against cardiomyocyte apoptosis in anoxia/reoxygenation （A/R） injury of neonatal rat. Methods： The model of A/R injury was finished through receiving anoxia for 2h ...Objective： To study protective effect of insulin against cardiomyocyte apoptosis in anoxia/reoxygenation （A/R） injury of neonatal rat. Methods： The model of A/R injury was finished through receiving anoxia for 2h and reoxygenation for 4h in cultured cardiomyocytes of neonatal rat. The cardiomyocytes were divided randomly into 3 groups： control group （CON）, anoxia/reoxygenation group （A/R） and insulin-treated group （INS）. At the end of reoxygenation of 4 hours, activities of lactate dehydrogenase （LDH）, contents of malondiaidehyde （MDA）, were assessed through spectrophotometric procedures, myocyte apoptosis were detected through TUNEL and DNA Ladder. Results： MDA, LDH, and Apoptosis Index were significantly decreased in INS group compared with A/R group （P〈0.01）. Conclusion： Insulin has a protective effect against A/R injury in cultured cardiomyocyte of neonatal rat; the protective mechanism may contribute to antiapoptosis of insulin.展开更多
Lake Victoria is the second (excl. Caspian Sea) largest lake in the world by surface area and 7th by Volume. The lake and catchment territories are shared between three countries, Kenya, Uganda and Tanzania. A researc...Lake Victoria is the second (excl. Caspian Sea) largest lake in the world by surface area and 7th by Volume. The lake and catchment territories are shared between three countries, Kenya, Uganda and Tanzania. A research was carried out during 1990-1992 exploring the changes of the thermo-chemical structure occurred after the invasion of Nile Perch. Results of changes of physico-chemical (Temperature, DO and pH) conditions are summarized in this paper. The anoxic conditions by space and time were enhanced. Enhancement of pollutant supply from anthropogenic developments of terrestrial sources and atmospheric dust deposition accompanied by the deleterious effects of the Nile Perch invasion caused enhancement of anoxia in the lake in space and time. The combination of bottom-up nutrient supply and strong mixing conditions, expressed as low RTR values accelerate phytoplankton growth rate and production. The surplus of organic matter originated from algal biomass, enhanced anoxia.展开更多
Numerous diseases and pathologies impair the delivery of oxygen to brain, with rapid and deleterious consequences. For example, diseases related to systemic hypoxemia （e.g., chronic pulmonary disorders, cystic fibro...Numerous diseases and pathologies impair the delivery of oxygen to brain, with rapid and deleterious consequences. For example, diseases related to systemic hypoxemia （e.g., chronic pulmonary disorders, cystic fibrosis）, decreased oxygen carrying capacity of blood （e.g., anemia）, or decreased transport （e.g., heart attack, stroke） can all reduce or entirely prevent the delivery of oxygen to brain cells, resulting in the initiation of programmed cell death pathways, necrosis, or excitotoxic cell death in brain （Pamenter, 2014）. However, oxygen-limited environments are common on earth and many organisms naturally experience periods of intermit- tent or prolonged hypoxia or anoxia in their daily and/or annual life cycles （Bickler and Buck, 2007）.展开更多
Introduction: Neonatal asphyxia (NA) is one of the most likely causes of neuro-developmental abnormalities in children. In Mali it is responsible for half of the early deaths and the third of neonatal mortality. Updat...Introduction: Neonatal asphyxia (NA) is one of the most likely causes of neuro-developmental abnormalities in children. In Mali it is responsible for half of the early deaths and the third of neonatal mortality. Updated data would help understand and improve intervention strategies to reduce mortality. Objective: It is the study of epidemiological and clinical characteristics, the immediate outcome and the factors associated with newborn (NB) mortality with NA. Material and Methods: This was a prospective cross-sectional study from June 27th to September 3rd 2016 about the NBs admitted for NA in the Hospital Teaching Gabriel Touré of Bamako. The clinical and biological data including the prognosis were collected from the health records of women, the liaison sheets and the medical file. The analysis was done using the software Epi info version 3.5.1. Results: 76 NBs were included which represented 23.45% of hospitalizations. The majority (89.5%, n = 68) were admitted to less than 24 hours of life for NA grade III according to the Sarnat classification (43.4%, n = 33). The average age of mothers was 24.17 ± 5.5 years. Almost half (41.3%, n = 31) were primigravida. The most common obstetrical event was dystocia (64.5%, n = 49). The prognosis was poor in grade III anoxia in our patients (56%) of deaths. Conclusion: The périnatal anoxia (PA) is a major health issue in Mali because of its frequency and severity. Monitoring of pregnancies, delivery assisted by skillful and qualified personnel, mastery of neonatal resuscitation techniques are good means of prevention.展开更多
Here we report a detailed trace element study of the cherts from Liuchapo Formation, which is a terminal Ediacaran (551-542 Ma) succession in South China deposited in deep-water basinal setting. The REE of Liuchapo ch...Here we report a detailed trace element study of the cherts from Liuchapo Formation, which is a terminal Ediacaran (551-542 Ma) succession in South China deposited in deep-water basinal setting. The REE of Liuchapo cherts shows similar features as observed for anoxic modern seawater (but not for hydrothermal fluids), characterized by positive La anomaly (LaN/CeN = 0.83–1.91, average 1.37), moderately negative Ce anomaly (0.53–1.1, average 0.73), positive Gd anomaly (average 1.08), positive Y anomaly (average 1.21), and depleted LREE and MREE. In addition, the Liuchapo cherts have low ΣREE (3.36–56.13 ppm, average 20.6 ppm), low Al2O3, Ti, Th and Zr concentrations, and high Y/Ho ratios (up to 43.9). The redox-sensitive trace elements concentrations in the cherts do not correlate with detrital input proxies. All of these features suggest that the redox-sensitive trace elements in the cherts were authigenically concentrated in water column and their concentrations thus are excellent indicators of ancient redox conditions. Very low Th/U ratios, high V/(V+Ni) and Fe?/Al ratios, enrichments of redox-sensitive trace elements (U, V, Mo), and low concentration of Mn in the cherts imply anoxia in the deep seawater. Our data reveal that the terminal Ediacaran ocean was not completely oxidized and the deep ocean was still anoxic, at least in South China. We propose that although the oxidative events existed in the terminal Ediacaran oceans, decomposition of organic matter prolonged anoxia in the deep ocean.展开更多
Background Opioid preconditioning （PC） reduces anoxia/reoxygenation （A/R） injury to various cells. However, it remains unclear whether opioid-induced delayed PC would show anti-apoptotic effects on pulmonary arter...Background Opioid preconditioning （PC） reduces anoxia/reoxygenation （A/R） injury to various cells. However, it remains unclear whether opioid-induced delayed PC would show anti-apoptotic effects on pulmonary artery endothelial cells （PAECs） suffering from A/R injury. The present study was conducted to elucidate this issue and to investigate the potential mechanism of opioid-induced delayed PC. Methods Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour reoxygenation 24 hours after pretreatment with saline （NaCI; 0.9%） or morphine （1 μmol/L）. To determine the underlying mechanism, a non-selective KATe channel inhibitor glibenclamide （Glib; 10 μmol/L）, a nitric oxide （NO） synthase blocker NG-nitro-L-arginine methyl ester （L-NAME; 100 μmol/L）, and an opioid receptor antagonist naloxone （Nal; 10μmol/L） were given 30 minutes before the A/R load. The percentage of apoptotic cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） staining, eNOS mRNA level was measured by real-time polymerase chain reaction （PCR）. NO content of PAECs supernatants was measured with the Griess reagent. Results Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced PAECs apoptosis （（18.1±1.9）% vs （5.5±0.3）%; P 〈0.05）, increased NO release （（11.4±1.3） μmol/L vs （20.5±2.1） μmol/L, P 〈0.05）, and up-regulated eNOS gene expression nearly 9 times （P 〈0.05）. The anti-apoptosis effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and Nal offset the enhanced release of NO caused by pretreatment with morphine. Conclusions Morphine-induced delayed PC prevents A/R injury of PAECs. This effect may be mediated by activation of KATe channel via opioid receptor and NO signaling pathways.展开更多
目的研究高原地区脑小血管病(cerebral small vessel disease,CSVD)患者脑微出血(cerebral microbleeds,CMBs)的发生率及相关危险因素,为高原地区CSVD患者的预防和治疗提供依据。方法回顾性收集2022年1月至2023年12月西藏自治区人民医...目的研究高原地区脑小血管病(cerebral small vessel disease,CSVD)患者脑微出血(cerebral microbleeds,CMBs)的发生率及相关危险因素,为高原地区CSVD患者的预防和治疗提供依据。方法回顾性收集2022年1月至2023年12月西藏自治区人民医院神经内科诊断的CSVD患者共131例,其中男86例,女45例,年龄(55.3±17.2)岁。根据有无CMBs将患者分为有CMBs组和无CMBs组,比较两组患者临床资料的差异。采用多因素Logistics回归模型分析高原地区CSVD患者发生CMBs的影响因素。结果131例CSVD患者中37例(28.2%)存在CMBs,其中单纯脑叶型11例(8.4%)、深部/幕下型11例(8.4%)、混合型15例(11.5%)。多因素Logistic回归模型显示饮酒是CMBs发生的独立危险因素(OR=4.04,95%CI:1.11~31.65;P=0.047),去除单纯脑叶型患者的敏感性分析显示饮酒仍是CMBs发生的独立危险因素(OR=5.93,95%CI:1.11~31.65;P=0.037)。结论饮酒是高原地区CSVD患者中发生CMBs的独立危险因素。展开更多
Objective：To assess any direct effect of extract of Paris polyphylla Simth（EPPS）,a Chinese plant,on a cardiomyocyte subject to ischemia-reperfusion injury and to further elucidate its protective effect against myoc...Objective：To assess any direct effect of extract of Paris polyphylla Simth（EPPS）,a Chinese plant,on a cardiomyocyte subject to ischemia-reperfusion injury and to further elucidate its protective effect against myocardium ischemia on the cellular level.Methods：Neonatal rat cardiomyocytes were isolated and subjected to an anoxia-reoxia injury simulating the ischemia-reperfusion injury in vivo in the presence or absence of EPPS or diltizem,a positive control.The lactate dehydrogenase（LDH） activities in culture supematants and cell viabilities were analyzed using the enzymatic reaction kinetics monitoring-method and MTT method, respectively.Free intracellular calcium concentrations and activities of Na~＋-K~＋ ATPase and Ca^（2＋） ATPase in cells were also measured with laser confocal microscopy and the inorganic phosphorus-transformation method,respectively.Results：In cardiomyocytes subject to anoxia-reoxia injury,EPPS at 50-400 mg/L showed a concentration-dependent inhibition on LDH leakage and maintenance of cell viability,and the effect was significant at 275 and 400 mg/L（both P0.01）.In addition,EPPS at 275 and 400 mg/L significantly inhibited the increase in intracellular free calcium（both P0.01） as well as decreased the activities of Na~＋-K~＋ ATPase and Ca^（2＋） ATPase（P0.01,P0.05）.Conclusions：EPPS prevents anoxia-reoxia injury in neonatal rat cardiomyocytes in vitro by preservation of Na~＋-K~＋ ATPase and Ca^（2＋） ATPase activities and inhibition of calcium overload.The direct protective effect on cardiomyocytes may be one of the key mechanisms that underlie the potential therapeutic benefit of EPPS against myocardium ischemia.展开更多
The dynamic changes in CAP, and EP in the scale media were examined with single micropipet during anoxia and reventilation with oxygen. Also, the morphologic changes in IHC, OHC and synapse were observed in this exper...The dynamic changes in CAP, and EP in the scale media were examined with single micropipet during anoxia and reventilation with oxygen. Also, the morphologic changes in IHC, OHC and synapse were observed in this experiment. It was found that the amplitude of SP and EP values declined with alteration in polarity of these value. The changes in polarity and amplitude of SP followed the changes of CAP threshold induced by anoxia. The histologic examinations revcaled no cvidence of acetylcholinesterase (AChE) alteration in the synapse and no succinict dehydrogenase (SDH) changes in IHC appeared. However, the activity of SDH in the OHC decreased. The results suggest that the polarity and amplitude of SP were influenced passively by the changes of EP value. In addition, the change of SP polarity from positive tonegative during anoxia is due to the loss of mudulation process of OHC to IHC, while the SP polarity from negative to positive during the supply of oxygen is caused by regain of the modulation process of OHC.展开更多
Background A number of studies suggest that the expression of heat shock protein 70 （HSP70） induced by heat stress are associated with protection against ischemia-reperfusion injury. But the protective effects may b...Background A number of studies suggest that the expression of heat shock protein 70 （HSP70） induced by heat stress are associated with protection against ischemia-reperfusion injury. But the protective effects may be contaminated by other factors in the same stress. This study was conducted to explore the protective role of HSP70 expression in acute myocardial anoxia/reoxygeneration （A/R） injury with a liposome-mediated gene transfer technique for the introduction of pCDNA HSP70 into the neonatal rat myocardial cells. In addition, heat shock stress cytoprotection was also investigated for comparison. Methods The cultured primary neonatal rat myocardiocytes with an acute myocardial A/R injury model and the HS-treated rat myocardiocyte model were used. Three-day cultured myocardiocytes were randomly divided into four groups （n=8）： control group, A/R group, HS＋A/R group and pCDNA HSP70 ＋A/R group. A liposome-coated HSP70 pCDNA plasmid was transfected into the primary neonatal rat myocardiocytes; HSP70 mRNA and its protein were confirmed by reverse transcriptase polymerase chain reaction （RT-PCR） and Western blotting. The cell viability was assayed by monotetrazolium （MTT） and the lactate dehydrogenase （LDH） and creatine phosphokinase （CPK） activity of cells during incubation and the changes in cells ultrastructure were examined. NF-κB activity in the primary neonatal rat myocardiocytes was measured with flow cytometry. Results Compared with viability in the A/R group （（35.4±6.9）%） the cell viability in the HS＋A/R group （（72.8±11.6）%） and the pCDNA HSP70 ＋ A/R group （（76.3±12.2）%） was improved significantly （P〈0.05）. The activity of LDH and CPK was significantly elevated in the A/R group. However, in the HS＋A/R group and pCDNA HSP70 ＋A/R group, significant decreases in activity were observed. The cell ultrastructure of the A/R group cells was abnormal, whereas nearly normal ultrastructure was observed in HS＋A/R group and pCDNA HSP70＋A/R group. HSP70 mRNA and protein were slightly expressed in the myocardiocytes of the A/R group. However, obvious overexpression was observed in the HS＋A/R group and in the pCDNA HSP70＋A/R group （P〈0.01）. And there was a significant difference between the HS＋A/R group and the pCDNA HSP70＋A/R group in the expression of HSP70 mRNA and protein （P〈0.01）. A high activity of NF-κB （5.76±0.64） was detected in the A/R group. But in the HS＋A/R group there was a statistically significant decrease in the activity of N F-KB compared with the A/R group （3.11±0.52 vs 5.76±0.64, P〈0.01 ）. The same statistically significant difference was also observed in the pCDNA HSP70 ＋ A/R group and A/R group （2.83±0.49 vs 5.76±0.64, P〈0.01 ）. Conclusions Overexpression of HSP70 alone by gene transfection leads to protection for cardiac myocyte against anoxia-reoxygeneration. These cardioprotective effects were related to the reduction in activation of NF-κB.展开更多
Cardiomyopeptidin (CMP), a small molecular polypeptide, is a new drug extracted from pig myocardium. Recently, evidence of its protective effect on myocardium injured by ischemia or anoxia has appeared.^(1,2) Neurons ...Cardiomyopeptidin (CMP), a small molecular polypeptide, is a new drug extracted from pig myocardium. Recently, evidence of its protective effect on myocardium injured by ischemia or anoxia has appeared.^(1,2) Neurons are also vulnerable to ischemia/anoxia. The aim of this study was to evaluate the neuroprotection of CMP in an anoxic model, which was the cultured hippocampal neurons in vitro, and to determine the relationship between CMP and expression of Bcl-2.展开更多
The mechanism of reperfusion injury of ischemic myocardium is not clear yet, and there has not been effective therapeutic methods up to now. Recently, growing evidence shows that the myocardial ischemia-reperfusion in...The mechanism of reperfusion injury of ischemic myocardium is not clear yet, and there has not been effective therapeutic methods up to now. Recently, growing evidence shows that the myocardial ischemia-reperfusion injury is similar in pathologic character and展开更多
基金supported by the National Key Basic Research Program of China(2013CB530900)the National Natural Science Foundation of China(81371400 and 81771416)Shanghai Municipal Commission of Health and Family Planning(201740153)
文摘Stroke is a leading cause of death worldwide. Up to one thousand potential drugs or interventions have been developed to treat stroke, out of which;60 have gone on to clinical trials. However, none of them has been successful. New insights into the molecular and cellular mechanisms of ischemia-induced injury are needed for discovering new therapeutic targets. Recently, Drosophila has been used to uncover new hypoxia-related genes. In this study, we describe an efficient and reliable assay with a sophisticated apparatus for studying the effects of oxygen deprivation on flies. Using this assay, wild-type flies were exposed to an anoxic environment for varying lengths of time, then the cumulative death rate and mobility recovery were systematically analyzed. We found that anoxia for over one hour caused lethality. The cumulative death rate on day 5 after anoxia was linearly and positively correlatedwith the duration of anoxia, and reached 50% when the duration was 2.5 h–3 h. We also found that the mobility recovery in normoxia was slow, as the climbing ability remained largely unchanged 4 h–6 h after 2.5-h of anoxia.We suggest that 2.5 h–3 h of anoxia and 4 h–6 h of recovery before mobility analysis are appropriate for future use of the anoxia assay.
基金Supported by the National Natural Science Foundation of China, No. 39900140
文摘AIM: To investigate the protective effect of isoflurane on energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation, and to compare isoflurane with halothane. METHODS: Hepatocytes freshly isolated from fed rats were suspended in Krebs-Henseleit buffer, and incubated in sealed flasks under O2/CO2 or N2/CO2 (95%/5%, V/V) for 30 or 60 min, followed by 5 or 10 min of reoxygenation, with an added volatile anesthetic or not. ATP, ADP, and adenosine monophosphate in hepatocytes were determined by high performance liquid chromatography, and energy charge was calculated. RESULTS: During 30 min of anoxia, the energy charge and total adenine nudeotide steadily increased with the isoflurane dose from 0 to 2 minimum alveolar anesthetic concentration (MAC), then decreased from 2 to 3 MAC. In short incubations (30-35 min) at 1 MAC isoflurane, energy charge modestly decreased during anoxia, which was partially prevented by isoflurane and completely reversed by reoxygenation, and total adenine nudeotide did not decrease. In long incubations (60-70 min), both energy charge and total adenine nudeotide greatly decreased during anoxia, with partial and no reversal by reoxygenation, respectively. Isoflurane partly prevented decreases in both energy charge and total adenine nudeotide during anoxia and reoxygenation. In addition, 1 MAC isoflurane obviously increased ATP/ADP, which could not be changed by 1 MAC halothane. CONCLUSION: Isoflurane partially protects isolated hepatocytes against decreases in both energy charge and total adenine nudeotide during short (reversible) or long (irreversible) anoxia.
基金supported by the Scientific Research Foundation of Health Department of Human Province(B2009-011)
文摘Objective:To explore the effect of emulsified isoflurane(EI)on apoptosis of anoxia-reoxygenation neonatal rat cardiomyocytea and relevant protein expression.Methods:Cardiac muscle anoxiareoxygenation damage model was established with culture in vitro neonatal rat cardiomyocytes.The cardiomyocytes were divided into control group,model group,fat emulsion group and EI group.The cardiomyocytes apoptosis rates and lactic dehydrogenase(LDH),superoxide dismutase(SOD)and malondialdehyde(MDA)index standardization were detected after relevant treatment The expression of apoptosis-related proteins Bel-2,Bax and Caspase-3 were detected with Western blot approach.Results:After hypoxia/reoxygenation(H/R)model was treated by EI,the cells apoptosis rate decreased and was dramatically below the fat emulsion group(P<0.05),Cardiomyocytes biochemical index detection presented that,compared with the control group that the LDH activity and MDA content dramatically increased(P<0.05),while the SOD activity notably decreased(P<0.05);compared with the H/R group,the SOD activity of the fat emulsion group and EI group increased(P<0.05);while the LDH activity and MDA content decreased(P<0.05).And the change of the EI group was more remarkable than the fat emulsion group(P<0.05).The Western blot analysis presented that,compared with the control group,the Bcl-2 protein expression of the other groups significantly decreased(P<0.05),the expressions of Bax protein and Caspase-3protein increased significantly(P<0.05);compared with H/R group,cardiomyocytes Bc1-2protein expression of EI group increased significantly(P<0.05),the expressions of Bax protein and Caspase-3 protein decreased significantly(P<0.05),and the change of EI group was more remarkable than the fat emulsion group(P<0.05).Conclusions:EI can inhabit the apoptosis of anoxia-reoxygenation damage model cardiomyocytes,and may he related to the up-regulation of expression of Bcl-2 and down-regulation of expression of Caspase-3 protein.
基金supported by grants from Natural National Science Foundation of China(No.81260023)National Science and Technology Infrastructure Program(No.2013BAI05B10)+1 种基金Graduate Innovation Special Fund of Jiangxi Province(No.YC2012-S029)Graduate Innovation Special Fund of Jiangxi Province(No.YC2014-B019)
文摘The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation（A/R） injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathway. We employed simulated A/R of neonatal rat ventricular myocytes（NRVM） as an in vitro model of ischemial/reperfusion（I/R） injury to the heart. NRVM were pretreated with four different concentrations of Rapamycin（20, 50, 100, 150 μmol/L）, and pretreated with 10 mmol/L 3-methyladenine（3MA） for inhibiting autophagy during A/R. Then, Western blot analysis was used to examine variation in the expression of LC3-Ⅱ, LC3-Ⅰ, Bim, caspase-3, p-PI3KⅠ, PI3KⅠ, p-Akt and Akt. In our model, Rapamycin had a preferential action on autophagy, increasing the expression of LC3-Ⅱ/ LC3-Ⅰ, whereas decreasing the expression of Bim and caspase-3. Moreover, our results also demonstrated that Rapamycin inhibited the activation of p-PI3KⅠ and enhanced the activation of p-Akt. It is concluded that Rapamycin has a cardioprotection effect by inducing autophagy in a concentration-dependent manner against apopotosis through PI3K/Akt signaling pathway during A/R in NRVM.
文摘Objective： To study protective effect of insulin against cardiomyocyte apoptosis in anoxia/reoxygenation （A/R） injury of neonatal rat. Methods： The model of A/R injury was finished through receiving anoxia for 2h and reoxygenation for 4h in cultured cardiomyocytes of neonatal rat. The cardiomyocytes were divided randomly into 3 groups： control group （CON）, anoxia/reoxygenation group （A/R） and insulin-treated group （INS）. At the end of reoxygenation of 4 hours, activities of lactate dehydrogenase （LDH）, contents of malondiaidehyde （MDA）, were assessed through spectrophotometric procedures, myocyte apoptosis were detected through TUNEL and DNA Ladder. Results： MDA, LDH, and Apoptosis Index were significantly decreased in INS group compared with A/R group （P〈0.01）. Conclusion： Insulin has a protective effect against A/R injury in cultured cardiomyocyte of neonatal rat; the protective mechanism may contribute to antiapoptosis of insulin.
文摘Lake Victoria is the second (excl. Caspian Sea) largest lake in the world by surface area and 7th by Volume. The lake and catchment territories are shared between three countries, Kenya, Uganda and Tanzania. A research was carried out during 1990-1992 exploring the changes of the thermo-chemical structure occurred after the invasion of Nile Perch. Results of changes of physico-chemical (Temperature, DO and pH) conditions are summarized in this paper. The anoxic conditions by space and time were enhanced. Enhancement of pollutant supply from anthropogenic developments of terrestrial sources and atmospheric dust deposition accompanied by the deleterious effects of the Nile Perch invasion caused enhancement of anoxia in the lake in space and time. The combination of bottom-up nutrient supply and strong mixing conditions, expressed as low RTR values accelerate phytoplankton growth rate and production. The surplus of organic matter originated from algal biomass, enhanced anoxia.
基金supported by Natural Sciences and Engineering Research Council of Canada Discovery grant and a Parker B Francis Fellowship to MEP
文摘Numerous diseases and pathologies impair the delivery of oxygen to brain, with rapid and deleterious consequences. For example, diseases related to systemic hypoxemia （e.g., chronic pulmonary disorders, cystic fibrosis）, decreased oxygen carrying capacity of blood （e.g., anemia）, or decreased transport （e.g., heart attack, stroke） can all reduce or entirely prevent the delivery of oxygen to brain cells, resulting in the initiation of programmed cell death pathways, necrosis, or excitotoxic cell death in brain （Pamenter, 2014）. However, oxygen-limited environments are common on earth and many organisms naturally experience periods of intermit- tent or prolonged hypoxia or anoxia in their daily and/or annual life cycles （Bickler and Buck, 2007）.
文摘Introduction: Neonatal asphyxia (NA) is one of the most likely causes of neuro-developmental abnormalities in children. In Mali it is responsible for half of the early deaths and the third of neonatal mortality. Updated data would help understand and improve intervention strategies to reduce mortality. Objective: It is the study of epidemiological and clinical characteristics, the immediate outcome and the factors associated with newborn (NB) mortality with NA. Material and Methods: This was a prospective cross-sectional study from June 27th to September 3rd 2016 about the NBs admitted for NA in the Hospital Teaching Gabriel Touré of Bamako. The clinical and biological data including the prognosis were collected from the health records of women, the liaison sheets and the medical file. The analysis was done using the software Epi info version 3.5.1. Results: 76 NBs were included which represented 23.45% of hospitalizations. The majority (89.5%, n = 68) were admitted to less than 24 hours of life for NA grade III according to the Sarnat classification (43.4%, n = 33). The average age of mothers was 24.17 ± 5.5 years. Almost half (41.3%, n = 31) were primigravida. The most common obstetrical event was dystocia (64.5%, n = 49). The prognosis was poor in grade III anoxia in our patients (56%) of deaths. Conclusion: The périnatal anoxia (PA) is a major health issue in Mali because of its frequency and severity. Monitoring of pregnancies, delivery assisted by skillful and qualified personnel, mastery of neonatal resuscitation techniques are good means of prevention.
基金National Natural Science Foundation of China (Grants Nos. 40532012, 40873007, 40603021)Chinese Academy of Sciences (Grant No. KZCX3- SW-141)
文摘Here we report a detailed trace element study of the cherts from Liuchapo Formation, which is a terminal Ediacaran (551-542 Ma) succession in South China deposited in deep-water basinal setting. The REE of Liuchapo cherts shows similar features as observed for anoxic modern seawater (but not for hydrothermal fluids), characterized by positive La anomaly (LaN/CeN = 0.83–1.91, average 1.37), moderately negative Ce anomaly (0.53–1.1, average 0.73), positive Gd anomaly (average 1.08), positive Y anomaly (average 1.21), and depleted LREE and MREE. In addition, the Liuchapo cherts have low ΣREE (3.36–56.13 ppm, average 20.6 ppm), low Al2O3, Ti, Th and Zr concentrations, and high Y/Ho ratios (up to 43.9). The redox-sensitive trace elements concentrations in the cherts do not correlate with detrital input proxies. All of these features suggest that the redox-sensitive trace elements in the cherts were authigenically concentrated in water column and their concentrations thus are excellent indicators of ancient redox conditions. Very low Th/U ratios, high V/(V+Ni) and Fe?/Al ratios, enrichments of redox-sensitive trace elements (U, V, Mo), and low concentration of Mn in the cherts imply anoxia in the deep seawater. Our data reveal that the terminal Ediacaran ocean was not completely oxidized and the deep ocean was still anoxic, at least in South China. We propose that although the oxidative events existed in the terminal Ediacaran oceans, decomposition of organic matter prolonged anoxia in the deep ocean.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30371373）.
文摘Background Opioid preconditioning （PC） reduces anoxia/reoxygenation （A/R） injury to various cells. However, it remains unclear whether opioid-induced delayed PC would show anti-apoptotic effects on pulmonary artery endothelial cells （PAECs） suffering from A/R injury. The present study was conducted to elucidate this issue and to investigate the potential mechanism of opioid-induced delayed PC. Methods Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour reoxygenation 24 hours after pretreatment with saline （NaCI; 0.9%） or morphine （1 μmol/L）. To determine the underlying mechanism, a non-selective KATe channel inhibitor glibenclamide （Glib; 10 μmol/L）, a nitric oxide （NO） synthase blocker NG-nitro-L-arginine methyl ester （L-NAME; 100 μmol/L）, and an opioid receptor antagonist naloxone （Nal; 10μmol/L） were given 30 minutes before the A/R load. The percentage of apoptotic cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） staining, eNOS mRNA level was measured by real-time polymerase chain reaction （PCR）. NO content of PAECs supernatants was measured with the Griess reagent. Results Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced PAECs apoptosis （（18.1±1.9）% vs （5.5±0.3）%; P 〈0.05）, increased NO release （（11.4±1.3） μmol/L vs （20.5±2.1） μmol/L, P 〈0.05）, and up-regulated eNOS gene expression nearly 9 times （P 〈0.05）. The anti-apoptosis effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and Nal offset the enhanced release of NO caused by pretreatment with morphine. Conclusions Morphine-induced delayed PC prevents A/R injury of PAECs. This effect may be mediated by activation of KATe channel via opioid receptor and NO signaling pathways.
文摘目的研究高原地区脑小血管病(cerebral small vessel disease,CSVD)患者脑微出血(cerebral microbleeds,CMBs)的发生率及相关危险因素,为高原地区CSVD患者的预防和治疗提供依据。方法回顾性收集2022年1月至2023年12月西藏自治区人民医院神经内科诊断的CSVD患者共131例,其中男86例,女45例,年龄(55.3±17.2)岁。根据有无CMBs将患者分为有CMBs组和无CMBs组,比较两组患者临床资料的差异。采用多因素Logistics回归模型分析高原地区CSVD患者发生CMBs的影响因素。结果131例CSVD患者中37例(28.2%)存在CMBs,其中单纯脑叶型11例(8.4%)、深部/幕下型11例(8.4%)、混合型15例(11.5%)。多因素Logistic回归模型显示饮酒是CMBs发生的独立危险因素(OR=4.04,95%CI:1.11~31.65;P=0.047),去除单纯脑叶型患者的敏感性分析显示饮酒仍是CMBs发生的独立危险因素(OR=5.93,95%CI:1.11~31.65;P=0.037)。结论饮酒是高原地区CSVD患者中发生CMBs的独立危险因素。
基金Supported by the Major Scientific and Technological Specialized Project for"Significant New Formulation of New Drugs(No. 2009ZX09301,2009ZX09303-003)"
文摘Objective：To assess any direct effect of extract of Paris polyphylla Simth（EPPS）,a Chinese plant,on a cardiomyocyte subject to ischemia-reperfusion injury and to further elucidate its protective effect against myocardium ischemia on the cellular level.Methods：Neonatal rat cardiomyocytes were isolated and subjected to an anoxia-reoxia injury simulating the ischemia-reperfusion injury in vivo in the presence or absence of EPPS or diltizem,a positive control.The lactate dehydrogenase（LDH） activities in culture supematants and cell viabilities were analyzed using the enzymatic reaction kinetics monitoring-method and MTT method, respectively.Free intracellular calcium concentrations and activities of Na~＋-K~＋ ATPase and Ca^（2＋） ATPase in cells were also measured with laser confocal microscopy and the inorganic phosphorus-transformation method,respectively.Results：In cardiomyocytes subject to anoxia-reoxia injury,EPPS at 50-400 mg/L showed a concentration-dependent inhibition on LDH leakage and maintenance of cell viability,and the effect was significant at 275 and 400 mg/L（both P0.01）.In addition,EPPS at 275 and 400 mg/L significantly inhibited the increase in intracellular free calcium（both P0.01） as well as decreased the activities of Na~＋-K~＋ ATPase and Ca^（2＋） ATPase（P0.01,P0.05）.Conclusions：EPPS prevents anoxia-reoxia injury in neonatal rat cardiomyocytes in vitro by preservation of Na~＋-K~＋ ATPase and Ca^（2＋） ATPase activities and inhibition of calcium overload.The direct protective effect on cardiomyocytes may be one of the key mechanisms that underlie the potential therapeutic benefit of EPPS against myocardium ischemia.
文摘The dynamic changes in CAP, and EP in the scale media were examined with single micropipet during anoxia and reventilation with oxygen. Also, the morphologic changes in IHC, OHC and synapse were observed in this experiment. It was found that the amplitude of SP and EP values declined with alteration in polarity of these value. The changes in polarity and amplitude of SP followed the changes of CAP threshold induced by anoxia. The histologic examinations revcaled no cvidence of acetylcholinesterase (AChE) alteration in the synapse and no succinict dehydrogenase (SDH) changes in IHC appeared. However, the activity of SDH in the OHC decreased. The results suggest that the polarity and amplitude of SP were influenced passively by the changes of EP value. In addition, the change of SP polarity from positive tonegative during anoxia is due to the loss of mudulation process of OHC to IHC, while the SP polarity from negative to positive during the supply of oxygen is caused by regain of the modulation process of OHC.
文摘Background A number of studies suggest that the expression of heat shock protein 70 （HSP70） induced by heat stress are associated with protection against ischemia-reperfusion injury. But the protective effects may be contaminated by other factors in the same stress. This study was conducted to explore the protective role of HSP70 expression in acute myocardial anoxia/reoxygeneration （A/R） injury with a liposome-mediated gene transfer technique for the introduction of pCDNA HSP70 into the neonatal rat myocardial cells. In addition, heat shock stress cytoprotection was also investigated for comparison. Methods The cultured primary neonatal rat myocardiocytes with an acute myocardial A/R injury model and the HS-treated rat myocardiocyte model were used. Three-day cultured myocardiocytes were randomly divided into four groups （n=8）： control group, A/R group, HS＋A/R group and pCDNA HSP70 ＋A/R group. A liposome-coated HSP70 pCDNA plasmid was transfected into the primary neonatal rat myocardiocytes; HSP70 mRNA and its protein were confirmed by reverse transcriptase polymerase chain reaction （RT-PCR） and Western blotting. The cell viability was assayed by monotetrazolium （MTT） and the lactate dehydrogenase （LDH） and creatine phosphokinase （CPK） activity of cells during incubation and the changes in cells ultrastructure were examined. NF-κB activity in the primary neonatal rat myocardiocytes was measured with flow cytometry. Results Compared with viability in the A/R group （（35.4±6.9）%） the cell viability in the HS＋A/R group （（72.8±11.6）%） and the pCDNA HSP70 ＋ A/R group （（76.3±12.2）%） was improved significantly （P〈0.05）. The activity of LDH and CPK was significantly elevated in the A/R group. However, in the HS＋A/R group and pCDNA HSP70 ＋A/R group, significant decreases in activity were observed. The cell ultrastructure of the A/R group cells was abnormal, whereas nearly normal ultrastructure was observed in HS＋A/R group and pCDNA HSP70＋A/R group. HSP70 mRNA and protein were slightly expressed in the myocardiocytes of the A/R group. However, obvious overexpression was observed in the HS＋A/R group and in the pCDNA HSP70＋A/R group （P〈0.01）. And there was a significant difference between the HS＋A/R group and the pCDNA HSP70＋A/R group in the expression of HSP70 mRNA and protein （P〈0.01）. A high activity of NF-κB （5.76±0.64） was detected in the A/R group. But in the HS＋A/R group there was a statistically significant decrease in the activity of N F-KB compared with the A/R group （3.11±0.52 vs 5.76±0.64, P〈0.01 ）. The same statistically significant difference was also observed in the pCDNA HSP70 ＋ A/R group and A/R group （2.83±0.49 vs 5.76±0.64, P〈0.01 ）. Conclusions Overexpression of HSP70 alone by gene transfection leads to protection for cardiac myocyte against anoxia-reoxygeneration. These cardioprotective effects were related to the reduction in activation of NF-κB.
文摘Cardiomyopeptidin (CMP), a small molecular polypeptide, is a new drug extracted from pig myocardium. Recently, evidence of its protective effect on myocardium injured by ischemia or anoxia has appeared.^(1,2) Neurons are also vulnerable to ischemia/anoxia. The aim of this study was to evaluate the neuroprotection of CMP in an anoxic model, which was the cultured hippocampal neurons in vitro, and to determine the relationship between CMP and expression of Bcl-2.
文摘The mechanism of reperfusion injury of ischemic myocardium is not clear yet, and there has not been effective therapeutic methods up to now. Recently, growing evidence shows that the myocardial ischemia-reperfusion injury is similar in pathologic character and
