格列齐特联用羟苯磺酸钙对糖尿病视网膜病变大鼠PKC、VEGF、HIF-1α表达的影响

Effects of gliclazide combined with calcium dobesilate on the expression of PKC,VEGF and HIF-1α protein in retinas of diabetic model rats

目的 观察格列齐特联用羟苯磺酸钙对糖尿病视网膜病变(DR)大鼠蛋白激酶C(PKC)、低氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)表达的影响。方法 雄性SD大鼠55只,随机抽取9只作为正常对照组,其余给予高糖高脂饮食+腹腔注射链脲佐菌素建立糖尿病模型。将造模成功的大鼠随机分为糖尿病模型组、格列齐特组、羟苯磺酸钙组和格列齐特联合羟苯磺酸钙组。每两周测得各组大鼠的体重,各组按设计剂量灌胃给药,给药前和给药后测大鼠的空腹血糖,WesternBlot法检测视网膜组织中PKC、HIF-1α、VEGF相关蛋白表达。结果 经8周灌胃给药后的各项检测指标结果显示:与正常组相比,糖尿病模型组大鼠体重出现明显下降(P<0.01),羟苯磺酸钙给药组大鼠体重也表现出明显降低(P<0.01);与模型组相比,格列齐特给药组大鼠体重下降减弱(P<0.01),且格列齐特给药组大鼠空腹血糖显著降低(P<0.01);与模型组相比,格列齐特给药组大鼠视网膜病理性损伤得到明显改善,且格列齐特羟苯磺酸钙联合用药组改善作用更为明显;与模型组相比,格列齐特给药组中PKC(P<0.05)、HIF-1α(P<0.01)和VEGF(P<0.05)蛋白表达明显下调,联合用药组的VEGF蛋白表达下调较单个给药组更为明显。结论 格列齐特联用羟苯磺酸钙对糖尿病模型大鼠视网膜病变有明显改善作用,其机制可能与降低视网膜中VEGF的蛋白表达有关。

Objective To observe the effect of glipizide combined with calcium dobesilate on pathological changes in retinas of diabetic model rats,and to detect the effect of the combination on the protein expressions of protein kinase C,hypoxia inducible factor 1 alpha(HIF-1α),vascular endothelial growth factor(VEGF)in retina tissues. Methods 55 male SD rats were used,9 rats were randomly selected as normal control group,and the remaining rats were used to establish the type 2 diabetic model.The rats that met the criterion for the diabetic model were randomly divided into model group,Gliclazide group,Calcium Dobesilate group and Gliclazide combined with Calcium Dobesilate group.Weights of rats in each group were determined during drug delivery.Fasting blood glucose was measured by blood glucose meter before and after administration.The expression of PKC,HIF-1α and VEGF protein in retinas was detected by Western blot. Results Compared with the normal control group,the body weights of the rats in diabetic model group decreased significantly( P <0.01).The body weights of rats in calcium dobesilate group also decreased significantly( P <0.01).Compared with the diabetic model group,the weight loss of the rats in gliclazide treatment group decreased( P <0.01).Gliclazide treatment caused a significant decrease in fasting blood glucose( P <0.01),and also improved the pathological damage in retina.Such improvement was most obvious in the combination group.Gliclazide treatment significantly down-regulated the expression of PKC( P <0.05),HIF-1α( P <0.01)and VEGF( P <0.05)protein in retinas.Compared with the single drug treatment group,down regulation of VEGF protein expression was most obvious in the combined group. Conclusion Gliclazide combined with calcium dobesilate markedly improves the pathological damages in retinas of diabetic rats,and its mechanism is related to the down-regulated expression of VEGF protein in retina.