磺脲类药物对2型糖尿病大鼠心肌组织磺脲类药物受体表达的影响

Effect of Sulfonylurea compounds on Sulfonylurea receptor 2 expression in myocardium of diabetic Goto-Kakizaki rats

目的观察不同磺脲类药物对糖尿病大鼠心肌组织磺脲类药物受体(SUR2)表达的影响。方法将自发性糖尿病GK大鼠随机分为糖尿病对照组、胰岛素组、格列本脲组、格列吡嗪组、格列齐特组和格列美脲组各12 只,另设正常对照组12只。应用放射配体结合法检测SUR2,应用半定量逆转录聚合酶链反应(RT-PCR)检测SUR2 mRNA表达。结果经不同磺脲类药物干预第12周,糖尿病对照组、胰岛素组与正常对照组SUR2受体密度的差异无显著性;SUR2 mRNA表达水平较对照组稍下降,但差异无显著性。各磺脲类药物治疗组的SUR2受体密度较正常对照组和糖尿病对照组无明显变化;SUR2 mRNA表达水平亦无明显变化。第24周,糖尿病大鼠SUR2 mRNA表达水平较第12周呈下降趋势,也低于同期正常对照组大鼠,但差异仍无显著性;各磺脲类药物治疗组 SUR2受体密度无明显变化;SUR2 mRNA表达水平变化不大。结论自发性糖尿病GK大鼠所表现出的糖尿病状态不影响心肌SUR2表达水平;治疗剂量的磺脲类药物对糖尿病大鼠心肌组织SUR2的表达无明显影响。

Objective To observe the effects of long -term treatment with different sulfonylurea compounds on Sulfonylurea receptor 2 （SUR2） expression in myocardium of the Goto-Kakizaki （GK） rats. Methods The rats were allocated into six groups： the diabete model group, Glibenclamide group, Glipizide group, Gliclazide group, Glimepiride group and the positive control group （treated with insulin） ; with twelve in each group. And a normal control group was also set up containing same number of rats. The expression of SUR2 in the myocardium of the Goto-Kakizaki （GK） rat was investigated by radioligand binding assay. SUR2 mRNA expression in the myocardial cells of rats was detected through reverse transcriptase-polymerase chain reaction （RT-PCR）. Results After twelve weeks of sulfonylurea compounds interference the results indicated that there was no significant difference in the SUR2 receptor density （Bmax） and affinity （Kd） of either group （P〉0.05）. There was no significant difference in myocardial mRNA expression levels of SUR2 in the diabetic, the insulin-treated diabetic and control groups （P 〉 0.05）. Up to 24 weeks SUR2 comparison of all Sulfonylureas-treated diabetic and non-treated diabetic rats showed no significant change in mRNA levels of in the heart （P 〉 0.05）. Conclusion The diabetes itself does not affect the Sulfonylurea receptor （SUR2） expression in the myocardial tissues. Sulfonylureas dosage does not affect the receptor expression of SUR2. （Shanghai Med J, 2006, 29 ： 217-221）