塞来昔布对糖尿病大鼠视网膜血管内皮生长因子表达的影响

Effect of celecoxib on the expression of vascular endothelial growth factors in diabetic rats

目的：观察塞来昔布对糖尿病大鼠视网膜血管内皮生长因子（VEGF）表达的影响。方法：将36只大鼠用链脲佐菌素（STZ）腹腔注射制成糖尿病大鼠模型，随机分成糖尿病组（n=18）和塞来昔布灌胃组（n=18）。塞来昔布灌胃组大鼠经口灌胃塞来昔布50mg／kg；糖尿病组经口灌胃等体积生理盐水。另18只正常大鼠为正常对照组。3个月后处死全部大鼠，应用免疫组织化学技术检测视网膜VEGF蛋白表达，逆转录-多聚酶链式反应（RT-PCR）方法检测视网膜VEGFmRNA和环氧化酶（COX）-2m RNA的表达。结果：正常对照组视网膜VEGFmRNA和COX-2mRNA表达量少，VEGF免疫组织化学反应弱阳性，VEGF蛋白表达量低；糖尿病组较正常对照组视网膜VEGFmRNA和COX-2mRNA表达均上调（P〈0.05），VEGF免疫组织化学反应呈强阳性，VEGF蛋白表达增高（P〈0．01）；塞来昔布灌胃组较糖尿病组视网膜VEGFmRNA表达显著下降（P〈0．05），COX-2mRNA的表达无显著降低（P〉0．05），VEGF免疫组织化学反应阳性减弱，VEGF蛋白表达降低（P〈0．01）。结论：塞来昔布可通过抑制COX-2的活性进一步抑制STZ诱导的糖尿病大鼠视网膜VEGFmRNA及蛋白表达。

Objective To observe the effect of celecoxib on the expression vascular endothelial growth factors （VEGF） in diabetic rats. Methods Thirty-six wistar rats were used to establish the diabetic models by intraperitoneal injection with streptozotocin. The diabetic rats were divided into 2 groups： diabetic group （n=18） and celecoxib group （n= 18）. Celecoxib （50 mg/kg） was administered orally to the rats in celecoxib group and the physiological saline with the same volume was given orally to the rats in diabetic group. Eighteen else rats were in normal control group. All of the rats were executed 3 months later. The expression of VEGF protein was detected by immunohistochemistry method. Reverse transcription-polymerase chain reaction（RT-PCR） analysis was used to examine the expression of retinal VEGF mRNA and cyclooxygenase-2 mRNA. Results Lower positive expression of VEGF mRNA and cyclooxygenase-2 mRNA, weakly positive action of immunohistochemistry of VEGF, and lower expression of VEGF protein were detected in normal control group; in the diabetic group, the expression of VEGF mRNA and cyclooxygenase-2 mRNA increased obviously comparing with which in the control group （P〈 0. 05）, and the strongly positive action of immunohistochemistry of VEGF and increased expression of VEGF protein were detected （P〈0. 01）; in celecoxib group, the expression of VEGF mRNA was lower than that in the diabetic group （P〈0. 05）, the expression of cyclooxygenase-2 mRNA didn＇t decrease much （P〉0.05）, the positive action of immunohistochemistry of VEGF decreased, and the expression of VEGF protein decreased （P 〈 0. 01 ）. Conclusion By inhibiting the activation of cyclooxygenase-2, celecoxib can inhibit the expression of retinal VEGF mRNA and protein in diabetic rats induced by streptozotocin.