摘要
目的探讨泛素-蛋白酶体抑制剂MG132对糖尿病(diabetes mellitus,DM)大鼠视网膜上Smurf2及Smad7的表达的影响。方法选择健康雄性Wistar大鼠60只,按随机数字表法分为正常对照组、DM组和MG132干预组各20只。MG132干预组与DM组给予一次性腹腔注射50 mg/kg链脲佐菌素(streptozotocin,STZ),正常对照组一次性给予等体积的柠檬酸三钠-柠檬酸缓冲液(pH 4.5)腹腔注射。自第三天起,MG132干预组大鼠每天给予0.1 mg/kg MG132 DMSO液腹腔注射,正常对照组和DM组每天给予0.1 mg/kg DMSO液腹腔注射。分别于给药后第8周和第12周处死各组大鼠,完整摘除大鼠的左眼球制成眼杯,采用免疫组织化学的方法检测各组大鼠视网膜上Smurf2及Smad7蛋白的表达。结果正常对照组大鼠视网膜上Smurf2无表达或弱表达,Smad7蛋白高表达。MG132干预组和DM组大鼠视网膜上Smurf2的表达均较正常对照组明显增加(P<0.01),Smad7的表达均较正常对照组明显降低(P<0.01);MG132干预组大鼠视网膜上Smurf2的表达较DM组明显降低(q分别为20.37和40.96,均P<0.01),Smad7的表达较DM组明显增加(q分别为67.20和187.00,均P<0.01)。结论泛素-蛋白酶体抑制剂MG132能够通过抑制Smurf2的表达使DM大鼠视网膜上Smad7的降解减少,对DR的防治具有重要意义。
Objective To investigate the effects of ubiquitin-proteasome inhibitor, MG132,on Smurf2 and Smad7 expression in the retina of diabetes mellitus rats, and study the role of the ubiquitination degradation of Smurf2 and Smad7 with diabetic retinopathy （DR）. Methods Sixty male Wistar rats were randomly divided into three groups：normal control group, DM group and MG132 group. DM model was established by intraperitoneal injection of 50 mg/kg STZ. 0. 1 mg/kg of MG132 DMSO was intraperitoneal injected once a day in MG132 group and the same volume of DMSO was intraperitoneal injected once a day in normal control group and DM group af- ter modeling 3 days. At 8 weeks and 12 weeks, the rats were sacrificed and removed left eyeballs to make the eyecups. Smurf2 and Smad7 protein expression in the retina was examined by immunohistochemistry. Results In the normal control group, smurf2 was expressed weakly or was not expressed in rat retina, but smurf7 was highly expressed. Compared with the normal control group, the expression of Smurf2 was significantly elevated（P 〈 0. 01 ）, but the expression of Smad7 were significantly reduced in the DM group and the MG132 group （P 〈 0. 01 ）. At 8 weeks and 12 weeks, the expression of Smurf2 was significantly lower in the MG132 group compared with the DM group（q = 20. 37 and 40.96, respectively, all P 〈 0.01 ）, and the expression of Smad7 was significantly elevated in the MG132 group compared with the DM group（q = 67.20 and 187. 00, respectively, all P 〈 0.01 ）. Conclusions MG132 as one of the ubiquitin- proteasome inhibitor may be used to inhibit degradation of Smad7 through the expression of Smurf2 in rat retina with DM. It is of great significance for the prevention and control of DR.
出处
《实用医院临床杂志》
2013年第5期60-63,共4页
Practical Journal of Clinical Medicine
