目的 考察金芪降糖片聯(lián)合胰島素對2型糖尿病大鼠胰島素抵抗的改善作用及作用機制。方法 采用高脂飼料喂養(yǎng)聯(lián)合ip 3次小劑量（35 mg/kg）鏈脲霉素制備2型糖尿病大鼠模型，選擇空腹血糖值>11.1 mmol/L的大鼠進行后續(xù)實驗。模型大鼠隨機分為模型組、金芪降糖片（0.5 g/kg）組、胰島素（6.5 IU/kg）組和聯(lián)合給藥（金芪降糖片0.5 g/kg+胰島素6.5 IU/kg）組，另選取10只健康大鼠作為對照組。各組均每天給藥1次，連續(xù)給藥4周，檢測大鼠餐后2 h血糖并進行胰島素耐量試驗（ITT），Elisa方法檢測大鼠血清成纖維細(xì)胞因子21（FGF21）含量，Western Bloting檢測大鼠肝臟PPAR-α表達情況。結(jié)果 與對照組比較，模型組餐后血糖明顯升高（P<0.01），胰島素敏感性、肝臟PPAR-α均顯著降低（P<0.01），血清FGF21升高，但無顯著性差異；與模型組比較，聯(lián)合給藥能明顯降低2型糖尿病大鼠餐后血糖（P<0.01），顯著增加胰島素敏感性（P<0.05），顯著升高血清FGF21含量（P<0.01）、增加肝臟PPAR-α表達（P<0.01），且較兩藥單用效果更優(yōu)。結(jié)論 金芪降糖片聯(lián)合胰島素具有改善2型糖尿病大鼠胰島素抵抗、增加胰島素敏感性的作用，其機制可能與協(xié)同激活PPAR-α/FGF21信號有關(guān)。

Objective To evaluate the effect of Jinqi Jiangtang Tablet (JJT) combined with insulin on insulin resistance (IR) in type 2 diabetic rats and its mechanism. Methods The rat model of type 2 diabetes was replicated by high-fat feeding combined with three low-dose (35 mg/kg) ip injection of streptozotocin, and animals with fasting blood glucose value greater than 11.1 mmol/L were selected for follow-up experiments. Model rats were randomly divided into model group, JJT (0.5 g/kg) group, insulin (6.5 IU/kg) group, and combined administration (JJT 0.5 g/kg + insulin 6.5 IU/kg) group. The treatment groups were intervened once daily for four weeks with giving clinical equivalent dose of drugs. At the end of the intervention, the postprandial blood glucose was measured and the insulin tolerance test (ITT) was performed, the level of fibroblast growth factor21 (FGF21) in serum and the expression of PPAR-α in liver was detected by Elisa and Western Blotting respectively. Results Compared with control group, postprandial blood glucose was significantly increased in rat of model group (P<0.01), insulin sensitivity and liver PPAR-α expression were significantly decreased (P<0.01), serum FGF21 was increased, but there was no significant difference. As compared with model group, JJT combined with insulin could significantly reduce the level of postprandial blood glucose (P<0.01) and obviously increase insulin sensitivity of the diabetic rat (P<0.05), significantly increase the serum FGF21 level and the expression of PPAR-α in liver (P<0.01), and these effects were better than the two drugs use alone. Conclusion JJT combined with insulin may improve insulin resistance and increase insulin sensitivity in type 2 diabetic rat, and its mechanism may be related to synergistic activation of PPAR-α/FGF21 signaling.

長江學(xué)者和創(chuàng)新團隊發(fā)展計劃資助項目（IRT_14R41）