Diazoxide attenuates ischemia/reperfusion injuryvia upregulation of heme oxygenase-1 after liver transplantation in rats  

作　　者：Zhong Zeng Han-Fei Huang Fei He Lin-Xi Wu Jie Lin Ming-Qing Chen 

机构地区：[1]Organ Transplantation Center,the First Affili-ated Hospital of Kunming Medical College,Kunming 650032,Yunnan Province,China

出　　处：《World Journal of Gastroenterology》2012年第15期1765-1772,共8页世界胃肠病学杂志（英文版）

基　　金：Supported by Social Development Projects of Yunnan Province,No.2008CA026

摘　　要：AIM:To evaluate the effects of diazoxide on ischemia/reperfusion(I/R)-injured hepatocytes and further elucidate its underlying mechanisms.METHODS:Male Sprague-Dawley rats were randomized(8 for donor and recipient per group)into five groups:I/R group(4 h of liver cold ischemia followed by 6 h of reperfusion);heme oxygenase-1(HO-1)small interfering RNA(siRNA)group(injection of siRNA via donor portal vein 48 h prior to harvest);diazoxide(DZ) group(injection of DZ via donor portal vein 10 min prior to harvest);HO-1 siRNA+DZ group;and siRNA control group.Blood and liver samples were collected at 6 h after reperfusion.The mRNA expressions and protein levels of HO-1 were determined by reverse transcription polymerase chain reaction and Western blotting,and tissue morphology was examined by light and transmission electron microscopy.Serum transaminases level and cytokines concentration were also measured.RESULTS:We observed that a significant reduction of HO-1 mRNA and protein levels in HO-1 siRNA and HO-1 siRNA+DZ group when compared with I/R group,while the increases were prominent in the DZ group.Light and transmission electron microscopy indicated severe disruption of tissue with lobular distortion and mitochondrial cristae damage in the HO-1 siRNA and HO-1 siRNA+DZ groups compared with DZ group.Serum alanine aminotransferase,aspartate transaminase,tumor necrosis factor-αand interleukin-6 levels increased in the HO-1 siRNA and HO-1 siRNA+DZ groups,and decreased in the DZ group.CONCLUSION:The protective effect of DZ may be induced by upregulation of HO-1.By inhibiting expression of HO-1,this protection pretreated with DZ was abolished.AIM：To evaluate the effects of diazoxide on ischemia/reperfusion（I/R）-injured hepatocytes and further elucidate its underlying mechanisms.METHODS：Male Sprague-Dawley rats were randomized（8 for donor and recipient per group）into five groups：I/R group（4 h of liver cold ischemia followed by 6 h of reperfusion）;heme oxygenase-1（HO-1）small interfering RNA（siRNA）group（injection of siRNA via donor portal vein 48 h prior to harvest）;diazoxide（DZ） group（injection of DZ via donor portal vein 10 min prior to harvest）;HO-1 siRNA＋DZ group;and siRNA control group.Blood and liver samples were collected at 6 h after reperfusion.The mRNA expressions and protein levels of HO-1 were determined by reverse transcription polymerase chain reaction and Western blotting,and tissue morphology was examined by light and transmission electron microscopy.Serum transaminases level and cytokines concentration were also measured.RESULTS：We observed that a significant reduction of HO-1 mRNA and protein levels in HO-1 siRNA and HO-1 siRNA＋DZ group when compared with I/R group,while the increases were prominent in the DZ group.Light and transmission electron microscopy indicated severe disruption of tissue with lobular distortion and mitochondrial cristae damage in the HO-1 siRNA and HO-1 siRNA＋DZ groups compared with DZ group.Serum alanine aminotransferase,aspartate transaminase,tumor necrosis factor-αand interleukin-6 levels increased in the HO-1 siRNA and HO-1 siRNA＋DZ groups,and decreased in the DZ group.CONCLUSION：The protective effect of DZ may be induced by upregulation of HO-1.By inhibiting expression of HO-1,this protection pretreated with DZ was abolished.

关 键 词：Ischemia/reperfusion injury DIAZOXIDE Heme oxygenase-1 Liver transplantation RAT 

分 类 号：Q344[生物学—遗传学] Q95-331