非酒精性脂肪性肝炎大鼠肠道分泌液sIgA的变化

摘要

目的 探讨非酒精性脂肪性肝炎形成过程中小肠分泌液sIgA和血浆内毒素水平的变化.方法 32只SD大鼠随机均分为对照组和模型组,对照组用普通饲料喂养,模型组通过高脂饮食建立大鼠非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)模型,并分别在8、12周末处死每组大鼠各8只,测定大鼠小肠分泌液中sIgA的水平和门静脉血浆中内毒素水平,测定小肠组织匀浆中SOD的活性和MDA的含量,并测定大鼠血清中TG、TC、ALT、AST,HE 染色观察肝脏病理改变.结果 8、12周模型组较正常对照组大鼠血清TC、ALT、AST明显升高(P＜0.05),肝脏病理分别表现为单纯性脂肪肝、脂肪性肝炎.8周末时模型组大鼠门静脉血浆中内毒素、小肠分泌液中sIgA的水平与对照组相比无明显变化(P＞0.05);12周末大鼠NASH阶段与对照组相比小肠分泌液中sIgA的水平明显降低(P＜0.05),门静脉血浆中内毒素水平与对照组相比明显升高(P＜0.05).并且门静脉血浆内毒素水平与小肠分泌液中sIgA水平呈负相关(r=-0.873,P＜0.05).8、12周末时模型组大鼠小肠组织匀浆中SOD活性明显降低,MDA含量明显升高(P＜0.05).结论 非酒精性脂肪性肝炎形成过程中小肠分泌液中sIgA明显降低,说明肠道免疫屏障受损,并且可能与肠道脂质过氧化增强有关,可能是NASH发生发展的重要发病机制之一.%Objective To explore the changes of sIgA of intestinal mucosal fluid and serum levels of endotoxin in the progress of non-alcoholic steatohepatitis(NASH) in rats. Methods Thirty-two SD rats were randomly divided into control group and model group. The rats in control group were fed with normal diet. The rats in model group were fed with fat-rich diet to establish the model of non-alcoholic steatohepatitis. The 8 rats in each group were killed at the end of 8th, 12th week respectively. The serum level of endotoxin in portal vein and the level of sIgA in intestinal mucosal fluid were measured. The activity of SOD and the content of MDA in intestinal tissue were measured. And the serum levels of TG, TC, ALT and AST were observed. The pathology of liver was observed by HE stain. Results The serum levels of TC, ALT and AST were higher in model group than those in control group at 8, 12th week. The pathology of liver represented simple fatty liver and steatohepatitis respectively. At the end of 8th week, there was no marked change in the levels of endotoxin and sIgA between model group and control group (P ＞0.05). At the end of 12th week, serum level of endotoxin in model group was higher than that in control group (P ＜ 0. 05 ), the level of sIgA of intestinal macosal fluid in model group was lower than that in control group (P ＜ 0. 05 ). Serum level of endotoxin in portal vein had a negative correlation with the level of sIgA of intestinal mucosal fluid (r = - 0. 873, P ＜ 0.05 ). Compared with control group, the content of MDA was increased and the activity of SOD was decreased in intestinal tissue in model group at 8, 12th week ( P ＜ 0. 05 ). Conclusion The level of sIgA of intestinal mucosal fluid is decreased in rats with NASH. It suggests that the intestinal mucosa immune barrier function destruction exists, and it is possible concerned with the intestinal lipid peroxidation upgraded, which may be one of important factors in the the pathogenesis and progress of NASH.