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

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。

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

Objectives To investigate the correlation between PI3K/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 (PI3K inhibitor) and 740Y-P group (PI3K 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 PI3K/Akt pathway protein in rat myocardium was detected by Western blotting. Results As compared with control group, the levels of FT3, FT4, TNF-αand 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-PI3K/PI3K and p-Akt/Akt in myocardium were significantly reduced (P<0.05). As compared with model group, serum FT3, FT4, TNF-αand IL-6 levels, apoptotic ratio of myocardial cells, FBG and IRI were significantly increased in LY294002 group (P<0.05), while TSH, p-PI3K/PI3K and p-Akt/Akt were significantly reduced in LY294002 group (P<0.05). In 740Y-P group, serum FT3, FT4, TNF-αand IL-6 levels, apoptotic ratio of myocardial cells, FBG and IRI were significantly reduced (P<0.05), while TSH, p-PI3K/PI3K and p-Akt/Akt were significantly increased (P<0.05). Conclusions PI3K/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.