白藜芦醇通过高迁移率族蛋白B1抗大鼠肝脏缺血再灌注损伤的作用及机制

Effect and mechanism of resveratrol alleviates hepatic ischemia reperfusion injury by HMGB1 in rats

目的:探讨白藜芦醇对大鼠肝脏缺血再灌注损伤中高迁移率族蛋白B1(HMGB1)表达的影响及机制。方法:健康雄性SD大鼠30只随机分为3组,假手术对照(SC)组、肝脏缺血再灌注(HIR)组、白藜芦醇(Res)组。各组分别采集血液标本,处死动物收集肝组织标本。检测血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)和碱性磷酸酶(AKP)及炎症因子IL-6、TNF-α的变化。应用Western Blot及RT-PCR方法检测HMGB1、Toll样受体4(Toll-like receptor4,TLR4)蛋白及基因表达情况。光镜下观察经HE染色肝组织形态学变化。结果:与HIR组相比,Res使大鼠肝组织病理学变化明显改善,血清中反映肝脏功能学的指标ALT、AST及AKP的浓度明显降低,同时肝组织HMGBl、TLR4蛋白及mRNA的表达降低,血清中炎症因子IL-6和TNF-α含量亦显著降低。结论:白藜芦醇对肝脏缺血再灌注损伤的保护作用可能与其通过抑制HMGB1-TLR4信号通路,从而减少其下游促炎细胞因子表达,减轻再灌注过程中炎性反应有关。

AIM：To investigate the effect and mechanism of resveratrol on the expression of high mobility group box 1 in rats with hepatic ischemiareperfusion injury.METHODS：Thirty healthy male Sprague-Dawley （SD） rats were randomly divided into three groups：sham control （SC） group,hepatic ischemia reperfusion injury （HIR） group and resveratrol （Res） group.The blood samples and liver tissue samples were collected.The pathological changes of the liver were observed.Serum ALT,AST and AKP activity were detected as indicators of liver function damage and the content of TNF-α and IL-6 in serum were detected by ELISA.The expressions of HMGB1 and TLR4 protein and mRNA were determined by Western Blot and RTPCR.RESULTS：Compared with the HIR group,the pathological injury of the liver was significantly improved and the concentrations of serum AST,ALT and AKP were significantly lower in Res group （P 〈0.01）;meanwhile,the expression of HMGB1 and TLR4 protein and mRNA of hepatic tissue were decreased,serum inflammatory factors IL-6 and TNF-α were also significantly decreased （P 〈 0.01）.CONCLUSION：Resveratrol shows significant protective effect on hepatic ischemia reperfusion injury in rat.This may be related with inhibiting the HMGB1-TLR4 signaling pathway and alleviating the inflammatory response.