罗格列酮对重症急性胰腺炎大鼠肝脏的保护作用

目的 探讨过氧化物酶体增殖物激活受体γ(PPAR-γ)激动剂罗格列酮(rosiglitazone,ROSI)对大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)肝脏组织高迁移率族蛋白Bl(high mobility group box-1 protein,HMGB1)表达的影响.方法 雄性SPF级 Wistar 大鼠120只,随机(随机数字法)分为3组:假手术组(SO组)、SAP组、ROSI组.其中SAP组随机分为3 h,6 h,12 h和24 h组,每组20只.采用大鼠胆胰管逆行注射5%牛磺胆酸钠溶液制备SAP模型.检测血清淀粉酶(amylase,AMY)和肝功能(ALT,AST),观察胰腺和肝脏组织病理变化,逆转录-聚合酶链反应(RT-PCR)检测核因子-κB(nuclear factor-kappa B,NF-κB)mRNA表达水平,免疫印迹法(western blotting)检测肝脏HMGB1蛋白的表达水平.采用SPSS 16.0统计分析软件对数据进行q检验、单向方差分析和相关分析.结果 SAP组各时间点ALT、AST、肝脏组织病理评分和HMGB1蛋白表达均较SO组显著升高(P＜0.01);HMGB1蛋白表达水平与ALT、AST、胰腺和肝脏组织病理评分均呈正相关,与AMY水平无明显相关性(P＞0.05).ROSI组NF-κB mRNA和HMGB1蛋白水平、AMY、ALT、AST、胰腺和肝脏病理评分均低于SAP 24h组(P＜0.01).结论 SAP时,HMGB1作为晚期炎症介质,参与了肝损伤的病理生理过程.ROSI能显著抑制HMGB1的表达,对SAP肝损伤有明显保护作用.

Protective effect of rosiglitazone on liver injury in rats with severe acute pancreatitis

Objective To explore the therapeutic effects of peroxisome proliferator activating receptor γagonist-rosiglitazone on HMGB1 expression in liver tissue of rats with SAP. Method A hundred and twenty Wistar rats were randomly (random number) divided into the sham operation group(SO group, n = 20) ,SAP group ( n=80) and ROSI treatment group (n =20). SAP group were randomly further divided into the 3 h, 6h, 12 h and 24h subgroups with 20 rats in each group. SAP model was made by retrograde injection of 5 % sodium deoxycholate into the biliopancreatic duct. The serum amylase, AST and ALT, and pathological scores of pancreas and liver tissue were observed. The expression of NF-κB mRNA and the level of HMGB1 protein were investigated respectively by Reverse transcription polymerase chain reaction (RT-PCR) and Westem blot method, respectively. SPSS 16.0software was used to make one-way ANOVA, q -test and correlation analysis. Results Serum amylase, AST and ALT, and pathological scores of pancreas and liver tissue, and the level of HMGB1 protein were markedly increased in each subgroup of SAP compared with SO group ( P ＜ 0.01). The level of HMGB1 protein was positively correlated with the changes of AST, ALT and pathological scores of pancreas and liver tissue. Correlation was not found between HMGB1 and amylase. Treatment with ROSI could significantly reduce the expression of NF-κB mR-NA and the levels of HMGB1 protein, serum AMY, AST and ALT, and pathological scores of pancreas and liver tissue in comparison with 24 h subgroup of SAP (P ＜0.01). Conclusions As a late-acting mediator of inflammation, HMGB1 was involved in the pathophysiological process of SAP-related liver injury. ROSI can reduce the liver injury by inhibition of the expression of the HMGB1.