补肾通脉方对胰岛素抵抗大鼠胰岛素信号转导的影响

作者	单位
黄冬梅	华中科技大学同济医学院附属同济医院中西医结合研究所武汉430030
陆付耳	华中科技大学同济医学院附属同济医院中西医结合研究所武汉430030
黄光英	华中科技大学同济医学院附属同济医院中西医结合研究所武汉430030

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中文摘要:

目的 :观察补肾通脉方对高脂饮食诱导的胰岛素抵抗 (IR)模型大鼠肌肉和脂肪组织中胰岛素刺激后的胰岛素受体 (InsR)和胰岛素受体底物 1(IRS 1)酪氨酸磷酸化的影响。方法 :雄性Wistar大鼠随机分为正常组、模型组和治疗组 ,治疗组以纯中药制剂补肾通脉方进行干预 ;模型组和治疗组大鼠均用脂肪占总热卡含量 6 1%的高脂饲料饲养 8周 ,正常组喂以普通饲料 ;常规测定空腹血糖 (FBG)及葡萄糖负荷后 1、2h血糖 (BG 1h ,BG 2h) ,以放射免疫法测定空腹血清胰岛素 (Fins) ;采用免疫沉淀及Westernblot技术测其肌肉及脂肪组织中胰岛素刺激后的InsR和IRS 1酪氨酸磷酸化水平。结果 :与模型组比较 ,治疗组FBG虽无明显变化 ,但Fins显著降低 (P <0 0 1) ,因而胰岛素敏感指数 (ISI)明显升高 (P <0 0 1) ;治疗组BG 1h和BG 2h水平较模型组明显降低 (P <0 0 5 ,P <0 0 1) ;治疗组大鼠肌肉和脂肪组织中InsRβ亚单位和IRS 1酪氨酸磷酸化蛋白电泳条带密度明显增加。结论 :补肾通脉方对大鼠IR有显著的改善作用 ,其机制可能与提高IR大鼠肌肉和脂肪组织中InsR和IRS 1在胰岛素刺激后的酪氨酸磷酸化水平 ,改善胰岛素信号转导等环节有关。

英文摘要:

Objective: To investigate the effect of Bushen Tongmai recipe (BSTMR) on the tyrosine phosphorylation of insulin receptor (InsR) and insulin receptor substrate-1 (IRS-1) after insulin stimulation in muscle and fat tissues of insulin resistant (IR) rats induced by high-fat forage. Methods: Male Wistar rats were randomly divided into normal group (normal forage), model group (high fat forage, in which 61% calories were supplied by fat) and treated group (same forage as model group and treated with BSTMR). All animals were fed for 8 weeks, fasting blood glucose (FBG), blood glucose (BG) levels 1- and 2-hrs after glucose loading were determined routinely, serum fasting insulin (Ins) was determined with radioimmunoassay (RIA) and tyrosine phosphorylation level of InsR and IRS-1 in fatty and muscular tissues was measured by immunoprecipitation and Western blot. Results: Compared with the model group, FBG in the treated group changed insignificantly, but level of Fins decreased markedly (P<0 01), so the insulin sensitivity index was significantly elevated in the treated group (P<0 01), levels of BG 1- and 2-hrs after glucose loading in the treated group were greatly improved in comparison with those in the model group (P<0 05 and P<0 01 respectively). Meanwhile, the density of electrophoresis bands of tyrosine phosphorylated InsR and IRS-1 proteins in muscular and fatty tissues in the treated group increased obviously. Conclusion: BSTMR could attenuate the insulin resistance in rats, its pharmaceutical mechanisms might be closely related with the elevation of the tyrosine phosphorylation levels of InsR and IRS-1 in muscular and fatty tissues after insulin stimulation, and improvement of insulin signal transduction in target tissues.

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