异丙酚对大鼠肝缺血再灌注损伤时HMGB-1/TLR4信号通路的影响

Effect of propofol on HMGB1/TLR4 signaling pathway during hepatic ischemia-reperfusion injury in rats

目的评价异丙酚对大鼠肝缺血再灌注损伤时高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)信号通路的影响.方法清洁级健康雄性SD大鼠36只,3月龄,体重250~300 g,采用随机数字表法分为3组(n=12):假手术组(S组)、肝缺血再灌注组(I/R组)和异丙酚组(P组).采用夹闭肝门左叶、中叶肝动脉、门静脉lh,再灌注6h的方法制备大鼠肝缺血再灌注损伤模型.P组于缺血前20 min时经尾静脉泵注异丙酚12mg·kg^-1·h^-1至再灌注6h.于再灌注6h时处死大鼠取肝左叶组织,观察病理学结果并行肝组织病理学损伤评分,采用Western blot法检测HMGB1、TLR4、TNF-α和IL-6的表达.结果与S组比较,I/R组和P组肝组织病理学损伤评分升高,HMGB1、TLR4、TNF-α和IL-6表达上调(P<0.05);与I/R组比较,P组肝组织病理学损伤评分降低,HMGB1、TLR4、TNF-α和IL-6表达下调(P<0.05).结论异丙酚减轻大鼠肝缺血再灌注损伤的机制与阻断HMGB-1/TLR4信号通路,抑制炎性反应有关.

Objective To evaluate the effect of propofol on high-mobility group box 1 protein(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway during hepatic ischemia-reperfusion(I/R)injury in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 3 months,weighing 250-300 g,were divided into 3 groups(n=12 each)using a random number table method:sham operation group(group S),hepatic I/R group(group I/R)and propofol group(group P).Hepatic I/R injury was induced by occluding the portal vein and hepatic artery supplying the left and middle lobes of the liver for 1 h followed by 6-h reperfusion in anesthetized rats.Propofol was infused via the tail vein at a rate of 12 mg·kg^-1·h^-1 starting from 20 min before ischemia until 6 h of reperfusion in group P.The rats were sacrificed at 6 h of reperfusion,and the left lobe of the liver was removed for microscopic examination of the pathological changes which were scored and for determination of the expression of HMGB1,TLR4,tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-6)in liver tissues(by Western blot).Results Compared with group S,pathological scores of liver tissues were significantly increased,and the expression of HMGB1,TLR4,TNF-αand IL-6 was up-regulated in I/R and P groups(P<0.05).Compared with group I/R,pathological scores of liver tissues were significantly decreased,and the expression of HMGB1,TLR4,TNF-αand IL-6 was down-regulated in group P(P<0.05).Conclusion The mechanism by which propofol reduces liver I/R injury is associated with blocking HMGB-1/TLR4 signaling pathway and inhibiting inflammatory responses in rats.