肠源性内毒素水平与肝脏Toll样受体4表达在大鼠重症急性胰腺炎肝损伤中变化

Alterations of intestinal endotoxin level and liver expression of Toll-like receptor 4 in rats with liver injury caused by severe acute pancreatitis

目的:探讨肠源性内毒素(ET)与肝脏Toll样受体4(TLR4)表达在重症急性胰腺炎(SAP)肝损伤中的关系。方法:48只Wistar大鼠随机均分为模型组和对照组,模型组用逆行胰胆管注射5%牛磺胆酸钠法制作SAP模型,对照组行假手术。两组分别于术后3,6,12 h随机各取8只大鼠,收集胰腺、肝脏组织及外周动脉血,行病理学检查,检测血淀粉酶(AMY),谷丙转氨酶(ALT)和ET水平,并用Western blot法检测肝脏TLR4表达。结果:与对照组比较,模型组胰腺与肝脏病理学评分、血AMY,ALT,ET水平,以及肝组织TLR4蛋白表达水平均明显升高(均P<0.05),且各指标均随时间不断升高;对照组各指标在各时间点上无明显变化(均P>0.05);模型组肝脏TLR4蛋白表达水平与血ET呈明显正相关(r=0.863,P<0.01)。结论:SAP时血ET水平升高与肝脏TLR4蛋白的表达上调存在相关性,两者的相互作用可能参与了SAP肝损伤的机制。

Objective： To investigate the relationship between intestinal endotoxin（ET） and liver expression of Toll-like receptor 4（TLR4） in liver injury induced by severe acute pancreatitis（SAP）. Methods： Forty-eight Wistar rats were equally randomized into model group and control group.Rats in model group were subjected to retrograde cholangiopancreatic duct injection of 5% sodium taurocholate to induce SAP,while rats in control group underwent sham operation.At 3,6 and 12 h after surgery,8 rats at each time point were randomly taken from each group,and their pancreatic and liver tissues as well as peripheral arterial blood samples were collected.Pathological examinations were performed,and the blood levels of amylase（AMY）,alanine transaminase（ALT） and ET,as well as the TLR4 expression in liver were determined. Results： Compared with control group,the pathological scores for pancreatic and liver injury,blood levels of AMY,ALT and ET,and liver expression level of TLR4 protein in model group were all increased significantly（all P〈0.05）,and all above parameters were increased in a time-dependent manner.All the parameters in control group showed no significant alteration across time points（all P〈0.05）.In model group,there was a significant positive correlationship between liver TLR4 expression and blood ET level（r=0.863,P〈0.01）. Conclusion： Blood ET level increase is correlated with liver TLR4 up-regulation during SAP,and the interaction between ET and TLR4 may be involved in the mechanism of SAP-induced liver damage.