白芍总苷对脂肪肝大鼠增强胰岛素敏感性及抗脂肪肝作用

Effects of total glucosides of paeony on enhancing insulin sensitivity and antagonizing nonalcoholic fatty liver in rats

目的:研究白芍总苷对高脂诱导胰岛素抵抗-脂肪肝大鼠血糖、血脂、胰岛素抵抗及肝功能和肝细胞脂肪变性病理改变的作用。方法:采用高脂、高糖饲料喂养大鼠,饲养56 d;57d,测定大鼠空腹血糖(FBG)和口服糖耐量试验2 h血糖(OGTT-2 hBG),并依血糖和体重将大鼠均衡随机分为脂肪肝模型组、二甲双胍组(0.2 g.kg-1)、白芍总苷高剂量组(0.15 g.kg-1)和低剂量组(0.05 g.kg-1);连续灌胃给药28 d后,测定大鼠FBG,OG-TT-2hBG和血清胰岛素(Fins)水平,并计算胰岛素抵抗指数(HOMA-IRI)和胰岛素敏感指数(ISI);测定血浆三酰甘油(TC)、总胆固醇(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、游离脂肪酸(FFA)水平;测定天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆碱脂酶(ChE)和超氧化物歧化酶(SOD)活性以及丙二醛(MDA)含量等的变化,并评估肝组织脂肪变性。结果:与正常大鼠比较,模型组大鼠胰岛素含量和IRI明显升高(P<0.01),而ISI降低(P<0.01);FFA,TG,TC和LDL-C水平升高(P<0.01),HDL-C水平降低(P<0.05);SOD活性降低(P<0.01),MDA含量升高(P<0.05);AST,ALT和ChE活性增高(P<0.05,P<0.01);肝脏脂肪变性明显增强(P<0.01)。白芍总苷和二甲双胍均能不同程度地拮抗大鼠的高胰岛素血症和胰岛素抵抗(P<0.05,P<0.01);降低FFA,TG,TC和LDL-C水平以及提高HDL-C含量(P<0.05,P<0.01);降低AST,ALT和ChE活性(P<0.05,P<0.01);提高SOD活性(P<0.01),并降低MDA含量(P<0.05);二甲双胍能降低FBG和OGTT-2hBG含量,但白芍总苷对FBG和OGTT-2 hBG含量则未见明显改变。结论:白芍总苷对胰岛素抵抗-脂肪肝具有降低血脂和保肝作用,其作用机制可能与其提高胰岛素敏感性、降低血脂以及增强抗氧化能力有关。

Objective： To study the pathological changes of blood glucose, serum lipid, insulin resistance, liver function, liver cell denaturalization of total glucosides of paeony on nonalcoholic fatty liver rats caused by insulin resistance and discuss the acting mechanism. Method： Adult SD rats were maintained on high-fat-sugar-salt diet for 56 days. In the 57th day, their fasting blood glucose （FBG） and 2-hours blood glucose after oral glucose tolerance test （ OGTY-2 hBG） were mensurated, according to which and the weight the rats were divided randomly into nonalcoholic fatty liver model group, metformin group （0. 2g·kg^-1） and total glucosides of paeony group （high dosage 0. 15g·kg^-1, low dosage 0. 05g·kg^-1）. All the rats were still administered the same diet and given different drugs by intragastric administration for 28 days. In the 29th day, all of them were killed and the blood was sampled to measure the levels of blood glucose [ FBG, OGTT-2 hBG, fasting insulin （Fins） ] and serum lipid [ free fatty acids （ FFA）, triglyceride （TG）, total cholesterol （TC）, low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C）], then the HOMA insulin resistance index （ HOMA-IRI, fasting glucosexinsulin） and insulin sensitivity index （ISI） were counted. The activities of aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, cholinesterase （ChE）, superoxide dismutase （SOD） and the contents of malondialdehyde （MDA） were measured also. Livers were weighed and collected to be observed the pathological changes. Result： Compared with normal group, in nonalcoholic fatty liver model group the levels of Fins and IRI were increased obviously （P 〈 0.01 ）, ISI were decreased （ P 〈 0. 01 ） , FFA, TG, TC, LDL-C were increased （ P 〈 0. 01 ）, HDL-C were decreased （ P 〈 0. 05 ） ; the content of MDA were increased （P 〈 0. 05 ）, the activities of SOD were decreased （ P 〈 0. 01 ） ; AST, ALT and ChE were increased （P 〈0. 05, or P 〈0. 01 ）, the pathological changes of liver fat were severe（P 〈0. 01 ）. In glucosides of paeony group and mefformin group, hyperinsulinaemia and insulin resistence were resisted （P 〈0. 05, or P 〈0. 01 ） ; the levels of FFA, TG, TC, LDL- C were decreased and HDL-C were increased （ P 〈 0. 05, or P 〈 0. 01 ） ; the activities of AST, ALT, ChE were decreased （P 〈 0.05, or P 〈0.01） and SOD were increased （P 〈0. 01）. The contents of MDA were decreased （P 〈0. 05）. The levels of FBG and 2 hBG in mefformin group were decreased but in total glucosides of paeony group were not decreased obviously. Conclusion： Total glueosides of paeony may protect liver function and modulate serum lipid for the fatty liver rats caused by insulin resistance, and its action mechanism may be concerned with enhancing insulin sensitivity and antioxidative ability, decreasing serum lipid.