甲状腺功能亢进症模型大鼠心肌细胞PI3K/Akt通路与胰岛素抵抗的关系

The correlation between PI3K/Akt pathway and insulin resistance in cardiomyocytes of rat models of hyperthyroidism

目的探讨甲状腺功能亢进症模型大鼠心肌细胞PI3K/Akt通路与胰岛素抵抗的关系。方法建立甲状腺功能亢进症模型大鼠,随机分为模型组、LY294002组(PI3K抑制剂)、740Y-P组(PI3K激动剂),每组12只;另取12只SD大鼠设为对照组。分组处理后,酶联免疫吸附法(ELISA)检测甲状腺功能指标血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(TSH)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平;测定空腹血糖水平(FBG)、胰岛素抵抗指数(IRI);TUNEL染色检测心肌细胞凋亡情况;蛋白免疫印迹法检测大鼠心肌组织PI3K/Akt通路蛋白表达。结果与对照组比较,模型组大鼠血清FT3、FT4、TNF-α及IL-6水平、心肌细胞凋亡比例、FBG、IRI显著升高(P<0.05),TSH、心肌组织p-PI3K/PI3K及p-Akt/Akt显著降低(P<0.05);与模型组比较,LY294002组大鼠血清FT3、FT4、TNF-α及IL-6水平、心肌细胞凋亡比例、FBG、IRI升高(P<0.05),TSH、心肌组织p-PI3K/PI3K及p-Akt/Akt降低(P<0.05);740Y-P组大鼠血清FT3、FT4、TNF-α及IL-6水平、心肌细胞凋亡比例、FBG、IRI降低(P<0.05),TSH、心肌组织p-PI3K/PI3K及p-Akt/Akt升高(P<0.05)。结论PI3K/Akt通路可调控甲状腺功能亢进症模型大鼠胰岛素抵抗,激活该通路,可使甲状腺功能恢复正常,减轻炎症反应,抑制心肌细胞凋亡,改善胰岛素抵抗。

Objectives To investigate the correlation between PI3 K/Akt pathway and insulin resistance in cardiomyocytes of rat models of hyperthyroidism. Methods The rat models of hyperthyroidism was established, and they were randomly divided into model group, LY294002 group(PI3 K inhibitor) and 740 Y-P group(PI3 K agonist), with 12 rats in each group;another 12 SD rats were selected as control group. After grouping, levels of serum free triiodothyronine(FT3), free thyroxine(FT4), thyrotropin(TSH), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were detected by enzyme-linked immunosorbent assay(ELISA), fasting blood glucose(FBG) and insulin resistance index(IRI) were measured.Myocardial apoptosis was detected by TUNEL staining;and the expression of PI3 K/Akt pathway protein in rat myocardium was detected by Western blotting. Results As compared with control group, the levels of FT3, FT4, TNF-α and IL-6 in serum, apoptotic ratio of myocardial cells, FBG and IRI in the model group were significantly increased(P<0.05), while TSH, p-PI3 K/PI3 K and p-Akt/Akt in myocardium were significantly reduced(P<0.05). As compared with model group, serum FT3, FT4, TNF-α and IL-6 levels, apoptotic ratio of myocardial cells, FBG and IRI were significantly increased in LY294002 group(P<0.05), while TSH, p-PI3 K/PI3 K and p-Akt/Akt were significantly reduced in LY294002 group(P<0.05). In 740 Y-P group, serum FT3, FT4, TNF-α and IL-6 levels, apoptotic ratio of myocardial cells, FBG and IRI were significantly reduced(P<0.05), while TSH, p-PI3 K/PI3 K and p-Akt/Akt were significantly increased(P<0.05). Conclusions PI3 K/Akt pathway can regulate insulin resistance in hyperthyroidism model rats, activate this pathway, restore normal thyroid function, alleviate inflammation, inhibit myocardial apoptosis and improve insulin resistance.