PPARγ激动剂干预对急性胰腺炎小鼠肝损伤的影响

The effect of PPARγagonists in acute pancreatitis with hepatic injury

目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮对急性胰腺炎小鼠肝损伤的影响并对其机制进行初步研究。方法 72只健康雄性昆明小鼠分为3组,急性胰腺炎组(AP组)、罗格列酮预处理组(AP-ROS组)和生理盐水组(NS组),每组24只。分别于建模后6h、12h和24h处死小鼠,全自动生化分析仪检测血清淀粉酶、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平。运用RT-PCR方法检测肝脏组织NF-κB和PPARγmRNA表达,应用Western blot技术检测肝脏组织PPARγ和NF-κB p65蛋白表达。结果小鼠血清淀粉酶、ALT和AST水平在相对应的各时间点AP组比NS组明显升高(P<0.01),AP-ROS组较AP组明显降低(P<0.01)。AP组肝脏组织PPARγmRNA和蛋白表达在造模后6h和12h均低于NS组(P<0.05);AP-ROS组PPARγmRNA和蛋白表达在各时间点均明显高于AP组和NS组(P<0.01)。AP组肝脏组织NF-κB mRNA和NF-κB p65蛋白表达水平在各时间点与AP-ROS组和NS组相比较均升高(P<0.01)。结论 NF-κB与小鼠急性胰腺炎肝损伤有明显关系,PPARγ在肝损伤中的表达受到抑制;罗格列酮在AP早期能增强PPARγ表达,抑制NF-κB的表达。

Objective To observe the peroxidase body growth activated receptorγ（PPARγ）agonist rosiglitazone on acute pancreatitis in mice with hepatic injury and to investigate the mechanism of hepatic injury.Methods Seventy-two male Kunming mice were randomly allocated into three groups（24 cases for each group）：acute pancreatitis group（AP group）,rosiglitazone group（AP-ROS group）,saline group（NS group）.Mice were killed at 6,12 and 24h after induction of acute pancreatitis.Serum amylase,ALT and AST activities were measured.The expressions of NF-κB and PPARγmRNA were assessed by RT-PCR.The expressions of NF-κB and PPARγprotein were assessed by Western blot.Results Compared with NS group,serum amylase,ALT and AST levels at each time point significantly increased in AP group（P〈0.01）;serum amylase,ALT and AST levels in AP-ROS group were significantly lower than those in AP group（P〈0.01）.Compared with NS group,the expressions of liver PPARγmRNA and protein in AP group were markedly lower at 6h and 12h（P〈0.05）,and the expressions of PPARγmRNA and protein in AP-ROS group were significantly higher than those in NS group and AP group（P〈0.01）.The expressions of liver NF-κB mRNA and NF-κB p65 protein in AP group were significantly higher than those in NS group and AP-ROS group at all time points（P〈0.01）.Conclusion There are clear relationships between NF-κB and hepatic injury in acute pancreatitis.The expressions of PPARγin injuried hepatic decreased.Rosiglitazone can increase the expressions of PPARγand prevent the expressions of NF-κB in hepatic during the early phase of acute pancreatitis.