茵陈蒿汤对代谢综合征-脂肪肝大鼠增强胰岛素敏感性及抗脂肪肝作用

目的观察茵陈蒿汤(capillaris decoction)对高脂-高糖诱导代谢综合征(metabolic syndrome,MetS)-脂肪肝(fattyliver,FL)大鼠的防治作用及机制。方法 SD大鼠,雌雄各半,除空白对照组食用标准饲料和饮用蒸馏水外,其余动物随机喂饲富含高脂肪(25%)饲料和高蔗糖(10%)饮水,造模8周;然后将大鼠随机分为模型对照、silibinin150mg.kg-1以及茵陈蒿汤5.0g.kg-1及2.5g.kg-1两个剂量组;分别灌胃给药或蒸馏水,qd×4w,测定大鼠空腹血清胰岛素(Fins)、血糖(FBG)、三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、脂联素,天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆碱酯酶(ChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮合酶(NOS)和一氧化氮(NO),并计算胰岛素敏感指数(ISI)、胰岛素抵抗指数(IRI)及肝指数;光学显微镜下观察肝脏组织的病理学改变。结果 MetS-FL大鼠TC、FFA、TG、LDL-C、MDA、FBG和Fins含量升高,HDL-C、NO和脂联素含量下降,AST、ALT、ChE活性升高,NOS和SOD活性降低,ISI减弱,肝指数升高并呈脂肪肝组织病理改变,与正常对照组比较,差异有显著性(P<0.05或P<0.01)。茵陈蒿汤5.0g.kg-1及2.5g.kg-1以及silibinin150mg.kg-1处理MetS-FL大鼠后,不同程度地降低MetS-FL大鼠TC、FFA、TG、LDL-C、MDA、FBG、Fins含量和AST、ALT、ChE活性,升高HDL-C、NO和脂联素含量,增强ISI,肝指数下降并改善脂肪肝组织病理改变,差异有显著性(P<0.05或P<0.01)。结论茵陈蒿汤对抗MetS-FL大鼠IR、增强胰岛素敏感性、纠正高胰岛素血症,改善血糖-脂代谢紊乱,抑制氧化应激反应和肝细胞损伤,降低氨基转移酶和ChE活性,以及不同程度地改善脂肪肝组织的病理改变,是茵陈蒿汤拮抗代谢综合征-脂肪肝的部分作用机制。茵陈蒿汤抗脂肪肝效应显示量效关系。

Effects of Capillaris Decoction on Enhancing Insulin Sensitivity and Antagonizing Fatty Liver in Rats with Metabolic Syndrome

Objective To investigate the prevention and treatment effects and mechanism of capillaris decoction on metabolic syndrome(Met S)-fatty liver(FL) in rats caused by feeding high-fat and high-sugar diet.Methods Excluding the blank control group eating standard chow and distilled water,the rats were fed with high-fat and high-sugar diet for 8 weeks,and then were randomly divided into fatty liver model group,silibinin group(150 mg·kg-1),and two groups of capillaris decoction(high dosage 5.0 g·kg-1,low dosage 2.5 g·kg-1).All the rats were still administered the same diet and given different drugs by intragastric administration for 4 weeks.After absolute diet 24 h,the levels of fasting insulin(Fins),fasting blood glucose(FBG),2-hours blood glucose(2h BG) after oral glucose tolerance test(OGTT),triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),free fatty acid(FFA),malonaldehyde(MDA) were determined;the activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT),cholinesterase(ChE),and superoxide dismutase(SOD) were measured,as well as insulin sensitivity index(ISI),insulin resistance index(HOMA-IRI) and liver index were counted;livers were weighed and collected to be observed for liver histopathologic changes under light microscope.Results In MS-FL rats,the contents of FBG,OGTT-2h BG,TC,FFA,TG,LDL-C,MDA and Fins increased,the IRI and activities of AST,ALT,ChE,and liver index raised;ISI and activity of SOD were weakened,the contents of adiponectin was lowered in contrast to the normal control rats(P <0.05 or P <0.01);Livers histopathological change revealed adipose degeneration.The contents of FBG,OGTT-2h BG,TC,FFA,TG,LDL-C,MDA and Fins were lowered,the IRI and activities of AST,ALT,ChE,and liver index decreased,ISI and activity of SOD raised,the contents of adiponectin increased,these results were revealed by Silibinin 150 mg·kg-1 and the group of capillaris decoction 5.0 g·kg-1 compared with the MS-Ht rats(P <0.05 or P <0.01),and livers histopathological changes were ameliorated.Conclusions Capillaris decoction and silibinin are able to enhance the insulin sensitivity and modify hyperinsulinemia,antagonize disorder of lipid metabolism by down-regulating FFA,TG,TC,LDL-C and up-regulating HDL-C,adiponectin;augment the antioxidant capacity by increasing SOD and inhibiting form of MDA;relieve liver injury by interfering release of AST,ALT,ChE,the degrees of fatty liver lesion is depressed in MS-FL rats.The effects of capillaris decoction on anti-nonalcoholic fatty liver show dose-effect relationship.