胰高血糖素受体siRNA对糖尿病模型小鼠的降糖作用研究

Hypoglycemic Effect of GCGR siRNA on Diabetic Mice in Vivo

目的:设计合成胰高血糖素受体(GCGR)基因的siRNA序列,并考察其对糖尿病模型小鼠的降糖作用。方法:根据siR-NA设计原理设计了3条靶向GCGR的siRNA序列(siRNA-1、siRNA-2、siRNA-3)。在建立了糖尿病模型小鼠以及血糖检测方法的基础上,检测一次性高压快速静脉注射给药后连续8d的血糖含量,以及给药后第2天腹腔注射葡萄糖后30、60、90、120min时血糖含量,并计算AUC值(糖耐量测试);同时设立非靶向siRNA组为对照。结果:3条靶向性siRNA给药后第1天小鼠血糖含量即明显下降,之后虽有所回升,但是与给药前比较仍有降低,而对照组则未出现血糖降低的现象,反而有所升高;在糖耐量试验中,siRNA-1、siRNA-2、siRNA-3序列组及对照组AUC分别为964.5、3216.1、2606.9、4173.9min·mmo·lL-1,前3组对葡萄糖的生物利用度显著更高。结论:设计合成的3条靶向GCGR的siRNA序列经静脉注射给药后,可较为有效地改善模型小鼠的高血糖症状。

OBJECTIVE： To design siRNA sequence of GCGR and investigate its hypoglycemic effect on diabetic rats. METHODS： Three different siRNA sequences targeting to GCGR were designed （siRNA-1, siRNA-2, siRNA-3）. Diabetic model mice were induced and blood glucose detection method was developed. After medication of disposable hypertensive rapid injection, the contents of blood glucose were measured for 8 days. At the second day after above step model rats were intraperitoneally injected with glucose. The contents of blood glucose at 30, 60, 90 min and the value of AUC were calculated with non-targeted siRNA group as control. RESULTS： The level of blood glucose of rats in siRNA sequence groups decreased markedly at the first after medication but increased a bit later. The level of blood glucose was still lower than before medication. The level of blood glucose in control group was not decreased but increased. In glucose tolerance test the AUC of siRNA-1 sequence group, siRNA-2 sequence group, siRNA-3 sequence group and control group were 964.5 min·mmol·L^-1, 3 216.1 min·mmol·L^-1, 2 606.9 min·mmol·L^-1, 4 173.9 min·mmol·L^-1, respectively. The first three groups had better bioavailability towards glucose. CONCLUSION： The three siRNA sequences targeting to GCGR could effectively lower the level of blood glucose in diabetic mice after treatment.