FK506抑制HMGB1的释放减轻肝移植大鼠肝脏缺血再灌注损伤  

FK506 reduces liver ischemia-reperfusion injury in a rat model of autoiogous orthotopic liver transplantation by decreasing HMGB1 release

作　　者：陈峰[1] 王建[2] 张雅敏[2] 

机构地区：[1]天津医科大学一中心临床学院,天津市300070 [2]天津市第一中心医院肝胆外科,天津市300192

出　　处：《世界华人消化杂志》2017年第4期326-333,共8页World Chinese Journal of Digestology

基　　金：国家临床重点专科建设基金资助项目(器官移植);No.201354413;天津市应用基础与前沿技术研究计划资助项目;No.14JCYBJC24800;国家自然科学基金资助项目;No.81370576;中国肝炎防治基金会天晴肝病研究基金;No.TQGB20170123~~

摘　　要：目的研究他克莫司(tacrolimus,FK506)预处理对自体原位肝移植(autologous orthotopic liver transplantation,AOLT)大鼠肝脏缺血再灌注(ischemia reperfusion,IR)损伤的作用.方法将32只成熟的♂SD大鼠随机分为4组:假手术组(S组)、AOLT组、AOLT+FK506低剂量处理组(L组)、AOLT+FK506高剂量处理组(H组).术后6 h取材,检测4组大鼠血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)水平;观察肝组织病理学改变;测定高迁移率族蛋白B1(high mobility group box 1,HMGBl)的mRNA及蛋白表达情況.结果肝移植术后,L组和H组血清中的ALT、AST及炎症因子TNF-α、IL-6水平均显著低于AOLT组,但明显高于S组(P<0.05).肝组织病理表明,AOLT组肝血窦淤血、肝细胞坏死及炎症细胞浸润程度较显著,而L组和H组较AOLT组明显减轻.L组和H组中HMGB1mRNA及蛋白表达水平显著低于AOLT组,但高于S组(P<0.05).上述检测指标在L组和H组之间比较无显著差异.结论 FK506预处理可以显著降低AOLT大鼠肝脏HMGB1的表达,抑制炎症因子释放,减少细胞坏死,从而减轻肝脏IR损伤,保护移植肝脏.AIM To evaluate the effect of tacrolimus（FK506）pretreatment on liver ischemia-reperfusion injury in a rat model of autologous orthotopic liver transplantation（AOLT）.METHODS Thirty-two adult SD rats were randomly divided into four groups：sham-operated group（S）,AOLT group,low dose FK506-treated group（L）,and high dose FK506-treated group（H）.After 6 h of reperfusion,serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6）levels were detected using commercial assay kits.The histopathological changes in the rat liver were assessed by HE staining.The high mobility group box 1（HMGB1） expression was tested by immunohistochemistry,RT-qPCR and Western blot assays.RESULTS Compared with the S group,serum ALT,AST,TNF-α and IL-6 levels were markedly increased in the AOLT group,but decreased in the FK506-treated groups（P〈0.05）.The histopathological changes in the liver of rats in the AOLT group included hepatic sinusoidal congestion,neutrophil infiltration,and hepatocyte necrosis,which were alleviated in the L group and H group.Compared with the S,L and H groups,there was a marked increase in HMGB1 translocation and release in the AOLT group,but FK506 pretreatment（L and H groups） reduced the HMGB1 expression in hepatocytes.Compared with the S group,the expression of HMGB1 mRNA and protein also demonstrated a marked increase in the AOLT group,but decreased in the FK506 pretreatment groups.However,there was no significant difference in the above indicators between the L and H groups.CONCLUSION FK506 pretreatment has a protective effect against liver ischemia-reperfusion injury by inhibiting HMGB1 translocation and release,suppressing the release of inflammatory factors,and reducing hepatocyte necrosis in the AOLT rat model.

关 键 词：他克莫司 肝脏 自体原位肝移植 高迁移率族蛋白B1 肝保护 

分 类 号：R657.3[医药卫生—外科学]