大鼠非酒精性脂肪性肝病MTP活性表达变化

The changes on expression of MTP activity in NAFLD rats with high fat diet

目的探讨微粒体三酰甘油转移蛋白(MTP)对大鼠高脂性非酒精性脂肪性肝病(NAFLD)形成的影响。方法雄性Wistar大鼠随机分为对照组(NC)和高脂组(HF),NC组正常饲料喂养,HF组高脂饮食喂养12周,测定动物体重、肝湿重和肝指数,血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血清和肝三酰甘油(TG)、总胆固醇(TCH)和病理组织学观察肝脂肪变情况;使用稳态寿命荧光光谱法检测肝和小肠微粒体MTP活性,Western blot检测肝和小肠微粒体MTP蛋白表达。结果与NC组比较,肝细胞呈明显脂肪变性,肝小叶内可见炎性细胞浸润和空泡变性;HF组大鼠肝湿重、肝指数,血清ALT、AST、TCH,肝TG、TCH值明显升高(P<0.01,P<0.05);肝和小肠微粒体MTP活性和蛋白表达量明显降低(P<0.05)。结论高脂饮食诱导的大鼠NAFLD形成可能与抑制肝和小肠MTP活性及蛋白表达有关。

Objective To investigate potential effect of microsomal triglyceride transfer protein（ MTP） of liver and small intestine on nonalcoholic fatty liver disease（ NAFLD） rats with high fat diet. Methods Twenty male Wistar rats were randomly divided into two groups： normal control（ NC） group and high fat（ HF） group. The HF group was fed with high fat diet while the NC group with common diet for 12 weeks. The hepatic pathology,body weight,liver humid weight and liver index,levels of alanine aminotransferase（ ALT） and aspartate aminotransferase（ AST）,triglycerides（ TG）,total cholesterol（ TCH） in serum,and TG,TCH in liver were detected. MTP activities in heptic and small intestinal microsome were observed by fluorescence lifetime and steady state spectrometer,the level of MTP protein in heptic and small intestine were determined by western blot. Results Compared with NC group,the rats fed with high-fat diets showed that the key histological features of NAFLD,including pronounced hepatic steatosis,inflammatory cell infiltration,and hepatocyte balloonings,with significant increasing liver humid weight and liver index,and concentrations of serum AST,ALT,TCH and hepatic TG,TCH（ P 0. 01,P 0. 05）. MTP activities and protein levels in liver and small intestine were reduced（ P 0. 05）. Conclusion NAFLD rat induced by feeding of a high fat diet is potentially associated with the decrease of MTP activities and protein levels in heptic and small intestine microsome.