降脂理肝汤对非酒精性脂肪肝大鼠肠黏膜屏障的影响

Effects of Jiangzhi Ligan Decoction on Intestinal Mucosal Barrier in Rats with Non-alcoholic Fatty Liver Disease

目的观察降脂理肝汤对非酒精性脂肪肝大鼠肠黏膜屏障的影响,探讨降脂理肝汤干预非酒精性脂肪肝的机制。方法40只SD雄性大鼠随机分为正常组(10只)和造模组(30只),采用高脂饮食喂养复制非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)大鼠模型,造模组大鼠再随机分为高脂饮食模型组、降脂理肝汤低剂量及高剂量组(4.6、9.2g/kg),分别予以相应干预6周后取小肠和门静脉血液,检测肠黏膜结构、紧密连接蛋白(Occludin)和ZO-1蛋白水平以及血浆内毒素水平。结果与正常组比较,高脂饮食大鼠小肠绒毛稀疏且排列不整齐、小肠绒毛高度明显降低(P<0.01),Occludin和ZO-1蛋白表达水平显著降低(P<0.05),血浆内毒素水平显著上升(P<0.01)。与高脂饮食模型组比较,高剂量降脂理肝汤组小肠绒毛排列较整齐,断裂较少,绒毛高度显著升高(P<0.01),Occludin和ZO-1蛋白水平显著上升(P<0.05),血浆内毒素水平明显降低(P<0.01);而低剂量降脂理肝汤组仅显著降低了血浆内毒素水平(P<0.01)。结论降脂理肝汤干预非酒精性脂肪肝的机制可能与其改善小肠绒毛结构,恢复Occludin和ZO-1蛋白水平从而减轻肠黏膜屏障损伤,降低血浆中的内毒素水平有关。

Objective To explore the effects of Jiangzhi Ligan Decoction (JZLGT) on intestinal mucosal barrier in rats with non-alcoholic fatty liver disease (NAFLD),and to explore the intervention mechanism of JZLGT in NAFLD.Methods Forty male Sprague-Dawley (SD) rats were divided into a normal diet (ND) group (10 rats) and a model group (30 rats).NAFLD rat model was successfully replicated by high-fat diet (HFD) feeding.Then the 30 rats in the model group were randomly divided into a HFD model group,a JZLGT-Low group and a JZLGT-High group (treated with 4.6 and 9.2 g/kg,respectively).After 6 weeks of corresponding intervention,blood of intestine and portal vein was collected.The structure of intestinal mucosa,levels of Occludin,ZO-1 and plasma endotoxin were determined.Results Compared with the ND group,the villi of the small intestine in the HFD rats were sparse and irregularly ranged,with the length of the small intestinal villi dramatically decreased (P<0.01);the expression levels of Occludin and ZO-1 were significantly decreased (P<0.05),and the plasma endotoxin level was notably increased (P<0.01).Compared with the HFD model group,the villi of the small intestine in the JZLGT-High group were neatly ranged and less fractured,with the length of villi obviously increased (P<0.01);the levels of Occludin and ZO-1 were remarkably increased (P<0.05),and the plasma endotoxin level was significantly decreased (P<0.01).However,only the plasma endotoxin level was decreased significantly in rats of the JZLGT-Low group (P<0.01).Conclusion The intervention mechanism of JZLGT on NAFLD may be related to the structural improvement of small intestinal villi and the restored expression levels of Occludin and ZO-1 proteins,which can relieve the injury of intestinal mucosal barrier and decrease the level of plasma endotoxin.