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[摘要]
目的 考察金芪降糖片联合胰岛素对2型糖尿病大鼠胰岛素抵抗的改善作用及作用机制。方法 采用高脂饲料喂养联合ip 3次小剂量(35 mg/kg)链脲霉素制备2型糖尿病大鼠模型,选择空腹血糖值>11.1 mmol/L的大鼠进行后续实验。模型大鼠随机分为模型组、金芪降糖片(0.5 g/kg)组、胰岛素(6.5 IU/kg)组和联合给药(金芪降糖片0.5 g/kg+胰岛素6.5 IU/kg)组,另选取10只健康大鼠作为对照组。各组均每天给药1次,连续给药4周,检测大鼠餐后2 h血糖并进行胰岛素耐量试验(ITT),Elisa方法检测大鼠血清成纤维细胞因子21(FGF21)含量,Western Bloting检测大鼠肝脏PPAR-α表达情况。结果 与对照组比较,模型组餐后血糖明显升高(P<0.01),胰岛素敏感性、肝脏PPAR-α均显著降低(P<0.01),血清FGF21升高,但无显著性差异;与模型组比较,联合给药能明显降低2型糖尿病大鼠餐后血糖(P<0.01),显著增加胰岛素敏感性(P<0.05),显著升高血清FGF21含量(P<0.01)、增加肝脏PPAR-α表达(P<0.01),且较两药单用效果更优。结论 金芪降糖片联合胰岛素具有改善2型糖尿病大鼠胰岛素抵抗、增加胰岛素敏感性的作用,其机制可能与协同激活PPAR-α/FGF21信号有关。
[Key word]
[Abstract]
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.
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[基金项目]
长江学者和创新团队发展计划资助项目(IRT_14R41)