调脂积冲剂对高脂诱导肥胖大鼠肝脏IRS-1、IRS-2mRNA表达的影响

Influence of Tiaozhiji on IRS-1 and IRS-2mRNA in Liver of Obesity Rats Induced by High Fat

目的:观察调脂积冲剂对高脂饮食诱导的肥胖大鼠减肥降脂作用,观察对真胰岛素、游离脂肪酸(FFA)水平及肝脏组织胰岛素受体底物-1/-2(IRS-1、IRS-2)mRNA表达的影响,探讨调脂积冲剂改善胰岛素抵抗的相关减肥机制。方法:雄性SD大鼠65只,设正常对照组10只,其余55只用于造模。7周后,选择出高于正常组体重20%的肥胖大鼠并测量身长并计算Lee's指数,再随机分为调脂积冲剂组、荷丹片组及肥胖模型对照组。调脂积冲剂组、荷丹片组给予相应计量的调脂积冲剂、荷丹片混匀药液,模型组正常组给予相对计量的生理盐水。给药5周后的动物称体重,测体长,计算Lee's指数,测定大鼠TC、TG、FFA、FBG的含量,用ELISA试剂盒测空腹真胰岛素,用实时荧光定量RT-PCR检测肝脏组织胰岛素受体底物-1/-2 mRNA的表达水平。结果:调脂积冲剂组大鼠体重、Lee's指数低于肥胖模型组大鼠(P<0.05);调脂积冲剂组大鼠血清TC、TG水平低于肥胖模型组大鼠(P<0.05);调脂积冲剂组大鼠血清FFA水平明显低于肥胖模型组大鼠(P<0.01);调脂积冲剂组大鼠血清真胰岛素水平明显低于肥胖模型组大鼠(P<0.05);调脂积冲剂组大鼠肝脏组织胰岛素受体底物-1(IRS-1)mRNA的表达水平明显高于肥胖模型组大鼠(P<0.05);肝脏组织胰岛素受体底物-2(IRS-2)mRNA的表达水平有一定升高,与肥胖模型组大鼠无明显差异(P>0.05)。结论:调脂积冲剂对肥胖大鼠具有减轻体重的作用;调脂积冲剂对肥胖大鼠具有调脂作用;可以降低肥胖大鼠血清FFA,可能是其治疗肥胖的作用机制之一;调脂积冲剂可以降低真胰岛素水平,增加肥胖大鼠肝脏组织胰岛素受体底物-1/-2(IRS-1、IRS-2)mRNA的表达,改善胰岛素抵抗,可能是其治疗肥胖的作用机制之一。

Objective ： The purpose of this study was to investigate the losing - weight and lowering - lipid. Effects of Tiaozhiji on obesity rats＇model induced by high fat diet were studied. The influence of Tiaozhiji on the expression levels of serum true insulin, free fatty acid（FFA） as well as mRNA expression of insulin receptor substrate - 1,2 （IRS - 1, IRS - ：2） within liver tissue, in order to probe mechanism of Tiaozhiji on improving insulin resistance to losing weight effects. Methods：65 male SD rats were chosen,in which 10 SD rats in normal group,while the other 55 SD rats should be built the model first. Seven weeks later, those obese rats with 20% higher weight than normal group were chosen, measuring body length and calculating Lee＇s index. And then those rats were randomly divided into 3 groups：Tiaozhiji group, Hedan Tablet group and obesity model control group. Tiaozhiji group and Hedan Tablet group were treated with corresponding doses of Tiaozhiji and Hedan Tablet,while model control group and normal group with corresponding doses of normal saline. After taking medicine for 5 weeks,all rats were measured the weight and length, calculating Lee＇s index and detecting the contents of TC, TG, FFA and FBG in rat serum. And then the fasting serum true insulin was detected by ELISA as well as mRNA expression of insulin receptor substrate - 1,2 within rats liver tissue detected by real -time fluorescence quantitative RT- PCR. Results：Rats＇weight and Lee＇s index in Tiaozhiji group were lower than those of obesity model group rats （P 〈 0. 05）. The levels of TC and TG within rat serum in Tiaozhiji group were lower than those of obesity model group （P 〈 0. 05）. The level of FFA in Tiaozhiji group was significantly lower than that of obesity model group （ P 〈 0. 01 ）. The level of serum true insulin in Tiaozhiji group was significantly lower than that of obesity model group （ P 〈 0.05 ） while FBG was without significant difference compared with obesity model group （ P 〉 0.05 ）. The mRNA expression of insulin receptor substrate - 1 （ IRS - 1 ） within rats liver tissue in Tiaozhiji group was increased, compared with that of obesity model group while mRNA expression of insulin receptor suhstrate - 2 （ IRS - 2 ） increased to some degree without significant difference compared with those of obesity model group （ P 〉 0.05 ）. Conclusion ： Tiaozhiji has the weight - losing and lipid - lowering function. Tiaozhiji has the function of lipid - lowering and can reduce serum FFA in fat rats, which might be one of the possible mechanisms of Tiaozhiji applied for the treatment of obesity. Tiaozhiji can reduce true insulin levels, increases the mRNA expression of insulin receptor substrate - 1,2 （ IRS - 1, IRS - 2 ） and improve insulin resistance, which might be one of the possible mechanisms of Tiaozhiji applied for the treatment of obesity.