薏苡仁提取物改善大鼠非酒精性脂肪肝游离脂肪酸的代谢机制研究

摘要

目的：：观察薏苡仁提取物对非酒精性脂肪肝的作用效果,从游离脂肪酸角度探讨薏苡仁提取物调节非酒精性脂肪性肝病的作用机制。方法：SD大鼠60只,随机分为6组,每组大鼠10只,分别为正常对照组、模型对照组、阳性对照组(血脂康胶囊,1 g·kg-1)、薏苡仁提取物高(20 g·kg-1)、中(10 g·kg-1)、低(5 g·kg-1)剂量组,正常对照组给予正常基础饲料喂养,其余5组大鼠均采用高脂饲料复制非酒精性脂肪性肝脏病变大鼠模型,造模时间为8周,从第5~8周开始药物干预治疗,观察薏苡仁提取物干预后对大鼠肝重、脂肪重及其指数的影响,检测血清总胆固醇( TC)、丙氨酸转移酶( ALT)、天冬氨酸转移酶( AST)、游离脂肪酸( FFA)、脂肪酸合成酶( FAS)、乙酰辅酶A羧化酶( ACCa-se)、丙二酰辅酶A( MALONYL-CoA)、单磷酸腺苷活化的蛋白激酶( AMPK)、脂联素( ADP)的含量。结果：模型对照组大鼠脂质代谢相关指标与正常对照组相比均出现显著异常(P<0.05),提示模型复制成功。药物干预治疗后,阳性对照组和薏苡仁水煎液3个剂量组均可不同程度的调整大鼠脂质代谢相关指标；与模型对照组相比,高剂量组和阳性对照组可显著提升TC、FFA、AMPK表达水平(P<0.05),降低ALT、AST、FAS、ACCa-se、MALONYL-CoA指标(P<0.05)；薏苡仁提取液3个剂量组均可明显降低NAFLD大鼠的体质量、肝湿重,改善相关指数。结论：薏苡仁水煎液具有显著改善高脂饮食诱导的大鼠非酒精性脂肪性肝病的药理效应；提高血清脂联素水平,改善低脂联素血症,再引起下游脂质代谢连锁反应；其改善大鼠非酒精性脂肪性肝病的游离脂肪酸代谢是通过调节“ADP-AMPK-ACCase-malony-CoA-FFA”脂质代谢通路实现的。%Objective:To observe the effect of coix seed extract on non-alcoholic fatty liver disease (NAFLD), and discuss the mechanism of coix seed extract in the treatment of NAFLD in the repect of free fatty acid. Methods:Totally 60 SD rats were randomly divided into 6 groups with 10 ones in each, the normal group, the model group, the positive group ( Xuezhikang capsules, 1 g · kg-1), three coix seed extract groups respectively at high (20 g·kg-1), medium (10 g·kg-1) and low (5 g·kg-1) dosage. The normal group was given basic diet, the other 5 groups were given high fat diet to establish NAFLD rat model, the modeling time was 8 weeks, and the drug treatment started from the 5th week till the 8th week. The liver weight and fat weight and index were observed after the drug intervention. The serum total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), fatty acid synthase (FAS), acetyl coenzyme A carboxylase (ACCa-se), C two acyl coenzyme A (MALONYL-CoA) , adenosine content of protein kinase ( AMPK) and adiponectin ( ADP) activated by glycosides were detected. Results: Com-pared with those in the normal group, the lipid metabolism related indices in the model group were significantly abnormal (P<0. 05), which suggested that the model was established successfully. After the drug intervention, the lipid metabolism related indicators in the positive group and the three drug groups were adjusted in varying degrees. Compared with those in the model group, TC, FFA and AMPK expression levels increased notably in the high dosage group and the positive group (P<0. 05), and the levels of ALT, AST, FAS, ACCa-se, MALONYL-CoA decreased at the same time (P<0. 05). Coix seed extract could decrease the body weight and liver wet weight in NAFLD rats and improve the related index significantly. Conclusion: The findings indicated that coix seed extract is highly effective in improving the pharmacological effect on NAFLD induced by high-fat diet, and the mechanism is achieved through ADP-AMPK-ACCase-malony-CoA-FFA axis.