AIM:To investigate the effects of the heme oxygenase(HO)-1/carbon monoxide system on iron deposition and portal pressure in rats with hepatic fibrosis induced by bile duct ligation(BDL).METHODS:Male Sprague-Dawley rat...AIM:To investigate the effects of the heme oxygenase(HO)-1/carbon monoxide system on iron deposition and portal pressure in rats with hepatic fibrosis induced by bile duct ligation(BDL).METHODS:Male Sprague-Dawley rats were divided randomly into a Sham group,BDL group,Fe group,deferoxamine(DFX) group,zinc protoporphyrin(ZnPP) group and cobalt protoporphyrin(CoPP) group.The levels of HO-1 were detected using different methods.The serum carboxyhemoglobin(COHb),iron,and portal vein pressure(PVP) were also quantified.The plasma and mRNA levels of hepcidin were measured.Hepatic fibrosis and its main pathway were assessed using Van Gieson's stain,hydroxyproline,transforming growth factor-β1(TGF-β1),nuclear factor-E2-related factor 2(Nrf2),matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-1(TIMP-1).RESULTS:Serum COHb and protein and mRNA expression levels of HO-1 and Nrf2 were increased in the BDL group compared with the Sham group and were much higher in the CoPP group.The ZnPP group showed lower expression of HO-1 and Nrf2 and lower COHb.The levels of iron and PVP were enhanced in the BDL group but were lower in the ZnPP and DFX groups and were higher in the CoPP and Fe groups.Hepcidin levels were higher,whereas superoxide dismutase levels were increased and malonaldehyde levels were decreased in the ZnPP and DFX groups.The ZnPP group also showed inhibited TGF-β1 expression and regulated TIMP-1/MMP-2 expression,as well as obviously attenuated liver fibrosis.CONCLUSION:Reducing hepatic iron deposition and CO levels by inhibiting HO-1 activity though the Nrf2/Keap pathway could be helpful in improving hepatic fibrosis and regulating PVP.展开更多
Background A fatal complication after liver transplantation is anastomotic embolization of the hepatic artery. In order to solve this problem, the portal venous arterialization （PVA） is used to reconstruct the hepat...Background A fatal complication after liver transplantation is anastomotic embolization of the hepatic artery. In order to solve this problem, the portal venous arterialization （PVA） is used to reconstruct the hepatic arterial blood flow. The purpose of this study was to investigate the influence of PVA on rats with acute occlusion of hepatic artery. Methods Rat PVA models were established and then randomly divided into Group 1 （control group）, Group 2 （jaundice group）, Group 3 （bile duct recanalization group）, and Group 4 （portal vein arterilization group）. Recanalization of the common bile duct and PVA were performed 5 days after bile duct ligation in the rats. The influence of the PVA on general conditions, hepatic changes of structure and function, portal vein pressure and hepatic micrangium were observed for one month. Results Five days after common bile duct ligation the serum bilirubin, transaminase and alkaline phosphatase levels were significantly increased. Compared with group 1, there was a statistically significant difference （P 〈0.01）. These rats then underwent bile duct recanalization and PVA. After a month, the liver functions and microscopic structures completely returned to normal and, compared with group 1, there was no statistically significant difference in portal vein pressure （P 〉0.05）. Vascular casting samples showed that hepatic sinusoids were slightly thicker and more filled than normal ones and although they had some deformations, the hepatic sinusoids were still distributed around the central vein in radial form. Conclusion Within a month after operation, bile duct recanalization and PVA do not show obvious adverse effects on liver hemodynamics and hepatic micrangium, and the liver function and microscopic structure can return to normal.展开更多
目的:基于中医“同身寸”理念,对以门静脉直径(PVD)≥1.3 cm作为提示门静脉高压症(PHT)的临界值进行个体化评估,说明P V D存在较大个体差异性,P V D在肝硬化不同个体应该存在不同临界值。方法:本研究基于文献学调研及2010年1月至2019年1...目的:基于中医“同身寸”理念,对以门静脉直径(PVD)≥1.3 cm作为提示门静脉高压症(PHT)的临界值进行个体化评估,说明P V D存在较大个体差异性,P V D在肝硬化不同个体应该存在不同临界值。方法:本研究基于文献学调研及2010年1月至2019年12月解放军总医院第五医学中心收治的640例肝硬化患者。将640例肝硬化患者分为PHT组(531例)和非PHT组(109例),其中PHT组有75例肝硬化患者行肝静脉压力梯度(HVPG)测定。在640例患者中,有168例患者通过收集既往病历获得了其未出现门脉高压前正常状态下PVD。结果:非PHT组中有86例患者的PVD≥1.3 cm。75例行HVPG测定的诊断为PHT的患者中,有7例有严重PHT患者的PVD<1.3 cm。在168例患者中,通过PVD≥1.3 cm作为临界值提示PHT与通过PVD个体化(△D)为修正提示PHT的ROC曲线下面积分别为0.692和0.763。△D与直接以PVD≥1.3 cm作为提示临界值的Z检验结果为Z=2.824,P<0.05。结论:通过对肝硬化患者门静脉宽度进行个体化修正,其PVD对肝硬化PHT的提示作用有所提升。展开更多
AIM:To investigate melatonin's preventive action in oxidative stress in a rat model with high fat diet-induced non-alcoholic fatty liver disease(NAFLD).METHODS:NAFLD was induced by high fat diet(HFD)in adult,male,...AIM:To investigate melatonin's preventive action in oxidative stress in a rat model with high fat diet-induced non-alcoholic fatty liver disease(NAFLD).METHODS:NAFLD was induced by high fat diet(HFD)in adult,male,Wistar rats,weighing 180-230 g.After acclimatization for one week,they were randomly assigned to 6 experimental groups that comprised animals on regular diet plus 5 or 10 mg/kg melatonin,for 4 or 8 wk;animals on HFD,with or without 5 or 10 mg/kg melatonin,for 4 or 8 wk;and animals on HFD for 8 or 12 wk,with melatonin 10 mg/kg for the last 4 wk.Liver damage was assessed biochemically by the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and histologically.Lipid peroxidation and oxidative stress were assessed by malondialdehyde and glutathione levels in liver tissue.Lipidemic indices and portal vein pressure were also measured.RESULTS:Compared to rats not receiving melatonin,rats on 5 or 10 mg/kg of melatonin had lower mean liver weight(-5.0 g and-4.9 g)(P < 0.001)and lower liver weight to body weight ratio(-1.0%)(P < 0.001),for the two doses,respectively.All rats fed HFD without melatonin developed severe,grade Ⅲ,steatosis.Rats on HFD with concurrent use of melatonin showed significantly less steatosis,with grade Ⅲ steatosis observed in 1 of 29(3.4%)rats on 10 mg/kg melatonin and in 3 of 27(11.1%)rats on 5 mg/kg melatonin.Melatonin was ineffective in reversing established steatosis.Melatonin also had no effect on any of the common lipidemic serum markers,the levels of which did not differ significantly among the rats on HFD,irrespective of the use or not of melatonin.Liver cell necrosis was significantly less in rats on HFD receiving melatonin than in those not on melatonin,with the AST levels declining by a mean of 170 U/L(P = 0.01)and 224 U/L(P = 0.001),and the ALT levels declining by a mean of 62.9 U/L(P = 0.01)and 93.4 U/L(P < 0.001),for the 5 and 10 mg/kg melatonin dose,respectively.Melatonin mitigated liver damage due to peroxidation and oxidative stress in liver t展开更多
基金Supported by Grants from the National Natural Science Foun-dation of China,No. 30970886The Science and Technology Project of Dalian,No. 2010E15SF179the Initial Doctoral funding of Liaoning Province,No. 20121110
文摘AIM:To investigate the effects of the heme oxygenase(HO)-1/carbon monoxide system on iron deposition and portal pressure in rats with hepatic fibrosis induced by bile duct ligation(BDL).METHODS:Male Sprague-Dawley rats were divided randomly into a Sham group,BDL group,Fe group,deferoxamine(DFX) group,zinc protoporphyrin(ZnPP) group and cobalt protoporphyrin(CoPP) group.The levels of HO-1 were detected using different methods.The serum carboxyhemoglobin(COHb),iron,and portal vein pressure(PVP) were also quantified.The plasma and mRNA levels of hepcidin were measured.Hepatic fibrosis and its main pathway were assessed using Van Gieson's stain,hydroxyproline,transforming growth factor-β1(TGF-β1),nuclear factor-E2-related factor 2(Nrf2),matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-1(TIMP-1).RESULTS:Serum COHb and protein and mRNA expression levels of HO-1 and Nrf2 were increased in the BDL group compared with the Sham group and were much higher in the CoPP group.The ZnPP group showed lower expression of HO-1 and Nrf2 and lower COHb.The levels of iron and PVP were enhanced in the BDL group but were lower in the ZnPP and DFX groups and were higher in the CoPP and Fe groups.Hepcidin levels were higher,whereas superoxide dismutase levels were increased and malonaldehyde levels were decreased in the ZnPP and DFX groups.The ZnPP group also showed inhibited TGF-β1 expression and regulated TIMP-1/MMP-2 expression,as well as obviously attenuated liver fibrosis.CONCLUSION:Reducing hepatic iron deposition and CO levels by inhibiting HO-1 activity though the Nrf2/Keap pathway could be helpful in improving hepatic fibrosis and regulating PVP.
文摘Background A fatal complication after liver transplantation is anastomotic embolization of the hepatic artery. In order to solve this problem, the portal venous arterialization （PVA） is used to reconstruct the hepatic arterial blood flow. The purpose of this study was to investigate the influence of PVA on rats with acute occlusion of hepatic artery. Methods Rat PVA models were established and then randomly divided into Group 1 （control group）, Group 2 （jaundice group）, Group 3 （bile duct recanalization group）, and Group 4 （portal vein arterilization group）. Recanalization of the common bile duct and PVA were performed 5 days after bile duct ligation in the rats. The influence of the PVA on general conditions, hepatic changes of structure and function, portal vein pressure and hepatic micrangium were observed for one month. Results Five days after common bile duct ligation the serum bilirubin, transaminase and alkaline phosphatase levels were significantly increased. Compared with group 1, there was a statistically significant difference （P 〈0.01）. These rats then underwent bile duct recanalization and PVA. After a month, the liver functions and microscopic structures completely returned to normal and, compared with group 1, there was no statistically significant difference in portal vein pressure （P 〉0.05）. Vascular casting samples showed that hepatic sinusoids were slightly thicker and more filled than normal ones and although they had some deformations, the hepatic sinusoids were still distributed around the central vein in radial form. Conclusion Within a month after operation, bile duct recanalization and PVA do not show obvious adverse effects on liver hemodynamics and hepatic micrangium, and the liver function and microscopic structure can return to normal.
文摘目的:基于中医“同身寸”理念,对以门静脉直径(PVD)≥1.3 cm作为提示门静脉高压症(PHT)的临界值进行个体化评估,说明P V D存在较大个体差异性,P V D在肝硬化不同个体应该存在不同临界值。方法:本研究基于文献学调研及2010年1月至2019年12月解放军总医院第五医学中心收治的640例肝硬化患者。将640例肝硬化患者分为PHT组(531例)和非PHT组(109例),其中PHT组有75例肝硬化患者行肝静脉压力梯度(HVPG)测定。在640例患者中,有168例患者通过收集既往病历获得了其未出现门脉高压前正常状态下PVD。结果:非PHT组中有86例患者的PVD≥1.3 cm。75例行HVPG测定的诊断为PHT的患者中,有7例有严重PHT患者的PVD<1.3 cm。在168例患者中,通过PVD≥1.3 cm作为临界值提示PHT与通过PVD个体化(△D)为修正提示PHT的ROC曲线下面积分别为0.692和0.763。△D与直接以PVD≥1.3 cm作为提示临界值的Z检验结果为Z=2.824,P<0.05。结论:通过对肝硬化患者门静脉宽度进行个体化修正,其PVD对肝硬化PHT的提示作用有所提升。
基金Supported by Grant from the Special Account for Research Funds (ELKE) of the National and Kapodistrian University of Athens,Greece,ref. 7493
文摘AIM:To investigate melatonin's preventive action in oxidative stress in a rat model with high fat diet-induced non-alcoholic fatty liver disease(NAFLD).METHODS:NAFLD was induced by high fat diet(HFD)in adult,male,Wistar rats,weighing 180-230 g.After acclimatization for one week,they were randomly assigned to 6 experimental groups that comprised animals on regular diet plus 5 or 10 mg/kg melatonin,for 4 or 8 wk;animals on HFD,with or without 5 or 10 mg/kg melatonin,for 4 or 8 wk;and animals on HFD for 8 or 12 wk,with melatonin 10 mg/kg for the last 4 wk.Liver damage was assessed biochemically by the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and histologically.Lipid peroxidation and oxidative stress were assessed by malondialdehyde and glutathione levels in liver tissue.Lipidemic indices and portal vein pressure were also measured.RESULTS:Compared to rats not receiving melatonin,rats on 5 or 10 mg/kg of melatonin had lower mean liver weight(-5.0 g and-4.9 g)(P < 0.001)and lower liver weight to body weight ratio(-1.0%)(P < 0.001),for the two doses,respectively.All rats fed HFD without melatonin developed severe,grade Ⅲ,steatosis.Rats on HFD with concurrent use of melatonin showed significantly less steatosis,with grade Ⅲ steatosis observed in 1 of 29(3.4%)rats on 10 mg/kg melatonin and in 3 of 27(11.1%)rats on 5 mg/kg melatonin.Melatonin was ineffective in reversing established steatosis.Melatonin also had no effect on any of the common lipidemic serum markers,the levels of which did not differ significantly among the rats on HFD,irrespective of the use or not of melatonin.Liver cell necrosis was significantly less in rats on HFD receiving melatonin than in those not on melatonin,with the AST levels declining by a mean of 170 U/L(P = 0.01)and 224 U/L(P = 0.001),and the ALT levels declining by a mean of 62.9 U/L(P = 0.01)and 93.4 U/L(P < 0.001),for the 5 and 10 mg/kg melatonin dose,respectively.Melatonin mitigated liver damage due to peroxidation and oxidative stress in liver t
