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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 receptor 4,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。
Objective: To investigate the effect and mechanism of resveratrol on high mobility group box 1 (HMGB1) expression during hepatic ischemia-reperfusion injury in rats. Methods: Thirty healthy male Sprague-Dawley rats were randomly divided into 3 groups: sham operation control group (SC), hepatic ischemia-reperfusion (HIR) group and resveratrol group. Blood samples were taken from each group, and animals were sacrificed to collect liver tissue samples. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) and inflammatory cytokines IL-6 and TNF-α were measured. Western Blot and RT-PCR were used to detect the protein and gene expression of HMGB1 and Toll-like receptor 4 (TLR4). The morphological changes of liver tissue were observed under light microscope. Results: Compared with HIR group, Res significantly improved the histopathological changes of liver in rats. The concentrations of serum ALT, AST and AKP in serum decreased significantly, while the expression of HMGB1, TLR4 protein and mRNA in liver decreased , Serum inflammatory cytokines IL-6 and TNF-α content also significantly reduced. CONCLUSION: The protective effect of resveratrol on liver ischemia-reperfusion injury may be related to its inhibition of HMGB1-TLR4 signaling pathway, thereby reducing the expression of pro-inflammatory cytokines downstream of it and reducing the inflammatory reaction during reperfusion.