大黄提取物治疗高糖-高脂诱导大鼠非酒精性脂肪性肝病作用及机制

目的 探讨大黄( rhubarb rhizomes,Rhub)提取物治疗高糖-高脂诱导大鼠非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的作用及机制.方法 Sprague-Dawley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NAFLD大鼠随机分为模型对照、水飞蓟宾(Silybin,Sily)0.15 mg/kg组以及Rhub 2.0g和1.0g/kg两个剂量组;分别 灌胃给药或蒸馏水,每天1次,连续4周;禁食24h后,处死大鼠,并收集血清,测定大鼠空腹血清胰岛素(Fins)、血糖(FBG)、甘油三酯(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(ADP),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)及肝指数;光学显微镜下观察肝脏组织的病理学改变.结果 NAFLD大鼠TC、TG、LDL-C、FFA、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,差异有统计学意义(P＜0.05或P＜0.01).Rhub 2.0g及1.0g/kg以及Silybin 0.15mg/kg处理NAFLD大鼠后,能不同程度地降低NAFLD大鼠TC、TG、LDL-C、FFA、MDA、FBG、Fins含量和AST、ALT、ChE活性,升高HDL-C、NO和ADP含量,增强ISI,肝指数下降并改善脂肪肝组织病理改变,差异有统计学意义(P＜0.05或P＜0.01).结论 Rhub和Silybin对抗NAFLD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,降低肝细胞膜漏出的氨基转移酶和ChE活性,改善肝内血管内皮功能,以及不同程度地改善脂肪肝组织的病理改变,是Rhub拮抗NAFLD的部分作用机制.Rhub以上效应显示量效关系.

The effect and mechanism of Rhubarb extract on administrating nonalcoholic fatty liver disease in high-sugar and high-fat diet-fed rats

Objective To observe the effect and mechanism of Rhubarb extract on administrating nonalcoholic fatty liver disease(NAFLD)in high-sugar and high-fat diet-fed rats.Methods Excluding the blank control group eating standard chow and distilled water,the others were fed with high-sugar and high-fat diet for 8 weeks,and then the rats were divided randomly into fatty liver model group,Silybin group(0.15 mg/kg),and two groups of Rhubarb extract(high dosage 2.0g/kg,low dosage 1.0g/kg).All the rats were still administered the same diet and given different drugs by intragastric administration for 4 week.After absolute diet 24 h,all the rats were executed and serum collected,the levels of fasting insulin(Fins),fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),free fatty acid(FFA),adiponectin(ADP),malondialdehyde(MDA),nitric oxide(NO) were detectd,and the activities of nitricoxide synthase(NOS),aspartate aminotransferase(AST),alanine aminotransferase(ALT),cholinesterase(ChE) and superoxide dismutase(SOD) were determined,as well as insulin resistance index(HOMA-IRI),insulin sensitivity index(ISI),and liver index were be counted,livers were weighed and collected to be observed the liver histopathologic changes under light microscope.Results In NAFLD rats,the contents of TC,TG,LDL-C,FFA,MDA,FBG and Fins were increased,HDL-C,NO and ADP were decreased,the activities of AST,ALT,ChE,and liver index were raised,ISI and activity of NOS,SOD were weakened,livers histopathological change was revealed adipose degeneration.They are diffferent from the normal control rats significantly(P<0.05 or P<0.01).The contents of TC,FFA,TG,LDL-C,MDA,FBG and Fins were lowed,the activities of AST,ALT,ChE,and liver index were decreased,ISI and activity of SOD were raised,the contents of ADP was increased,these results were revealed by Silybin 0.15 mg/kg and Rhubarb extract(2.0g/kg,1.0g/kg) compared with the NAFLD rats(P<0.05 or P<0.01),and livers histopathological changes were ameliorated.Conclusion Rhubarb and Silybin are able to antagonize the insulin resistance,enhance the insulin sensitivity,modify hyperinsulinemia,antagonize disorder of glucose-lipid metabolism,inhibit the oxidative stress reaction and liver injury,reduce the enzymes activities of liver cell membrane-exudated,reform the intrahepatic vascular endothelial function,improve the fatty liver pathological changes in different levels in NAFLD rats.These may be the part of the effective mechanism for Rhubarb to antagonize NAFLD.The effects of Rhubarb on anti-nonalcoholic fatty liver show dose-effect relationships.