摘要
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。
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.
出处
《临床医学工程》
2012年第4期520-523,共4页
Clinical Medicine & Engineering
基金
广东省医学科学技术基金(A2004546)资助
关键词
茵陈蒿汤
代谢综合征
非酒精性脂肪肝
胰岛素抵抗
高脂血症
氧化应激
Capillaris decoction
Metabolic syndrome
Nonalcoholic fatty liver
Insulin resistance
Hyperlipidemia
Oxidative stress
作者简介
钟成(1974-),男,主管中药师,从事中药学及药理实验研究。
通讯作者:潘竞锵(1956-),男,E-mail:pjq56@yahoo.com.cn。