金钗石斛多糖通过下调CYP2E1表达改善非酒精性脂肪肝病大鼠症状

Dendrobium nobile polysaccharide improves symptoms of NAFLD rats by down-regulating CYP2E1 expression

目的建立非酒精性脂肪肝病(NAFLD)大鼠模型,观察金钗石斛多糖对肝细胞色素P4502E1蛋白及mRNA表达的影响。方法选用SPF级,雄性SD大鼠60只,随机分为正常组、模型组、多烯磷脂酰胆碱组、金钗石斛多糖低、中和高剂量组6组,每组10只。高脂高糖饮食构建非酒精性脂肪肝病大鼠模型,给予相应治疗6周后,观察大鼠一般情况,提取肝脏检测肝脏病理学、肝组织CYP2E1蛋白和mRNA表达,收集血液检测天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆固醇(TC)、甘油三酯(TG)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活力。结果模型组出现一定的脂肪样变性,部分肝细胞有炎性因子浸润;与模型组相比,各治疗组均有改善。与正常组相比,模型组肝指数、AST、ALT、TG、TC、CYP2E1蛋白及mRNA明显升高,CAT和SOD明显降低(各P<0.05);与模型组相比,金钗石斛多糖三个剂量组和多烯磷脂酰胆碱组AST、ALT、TG、TC、CYP2E1蛋白及mRNA均明显降低(P<0.05),CAT和SOD明显升高(P<0.05),且金钗石斛多糖高剂量组TG和TC明显低于多烯磷脂酰胆碱组(P<0.05),金钗石斛多糖三个剂量组CYP2E1蛋白及mRNA明显低于多烯磷脂酰胆碱组(P<0.05)。结论金钗石斛多糖可明显降低NAFLD大鼠肝脏中CYP2E1蛋白及mRNA表达,进而改善肝功能和血脂水平,提高CAT和SOD活力,最终有效缓解NAFLD大鼠症状。

Objective To establish a rat model of nonalcoholic fatty liver disease(NAFLD) and observe the effect of Dendrobium nobile polysaccharide on the expression of cytochrome P4502 E1 protein and mRNA. Methods 60 male SD rats of SPF grade were randomly divided into normal group, model group, polyene phosphatidylcholine group, Dendrobium nobile polysaccharide low, medium and high dose group, 10 rats in each group. The model of nonalcoholic fatty liver disease was established by high fat and high sugar diet. After 6 weeks of treatment, the general situation of rats was observed, the liver pathology, the expression of CYP2 E1 protein and mRNA in liver tissue were detected, and the activities of aspartate aminotransferase(AST), alanine aminotransferase(ALT), cholesterol(TC), triglyceride(TG), catalase(CAT) and superoxide dismutase(SOD) in blood were detected. Results In the model group, there was a certain degree of fatty degeneration, and some hepatocytes were infiltrated with inflammatory factors. Compared with the model group, each treatment group improved. Compared with the normal group, the liver index, AST, ALT, TG, TC, CYP2 E1 protein and mRNA in the model group increased significantly, while CAT and SOD decreased significantly(P<0.05). Compared with the model group, AST, ALT, TG, TC, CYP2 E1 protein and mRNA in the three dose groups of Dendrobium nobile polysaccharide and polyene phosphatidylcholine group were significantly lower(P<0.05), CAT and SOD were significantly higher(P<0.05), and TG and TC in the high dose group of Dendrobium nobile polysaccharide were significantly lower than those in the polyene phosphatidylcholine group(P<0.05). The protein and mRNA of CYP2 E1 in three dosages of Dendrobium nobile polysaccharide group were significantly lower than those in polyene phosphatidylcholine group(P<0.05). Conclusion Dendrobium nobile polysaccharide can significantly reduce the expression of CYP2 E1 protein and mRNA in the liver of NAFLD rats, improve the liver function and blood lipid level, improve the activity of cat and SOD, and finally effectively alleviate the symptoms of NAFLD rats.