糖尿病早期NOS亚型的蛋白表达及其在血流变化中作用的实验研究

目的探讨在糖尿病早期,3种亚型一氧化氮合酶(NOS)在大鼠视网膜不同组织细胞中蛋白表达的变化,及其与视网膜血流变化的关系。方法将Wistar大鼠随机分成正常对照组与链脲佐菌素(STZ)腹腔注射诱导的糖尿病组各10只,采用彩色多谱勒对大鼠视网膜中央动脉(CRA)进行血流参数的测量,运用免疫组织化学技术观察视网膜eNOS、iNOS、nNOS蛋白表达的变化。结果8wk糖尿病大鼠视网膜尚未出现病变,但血流参数已显著异常,表现为糖尿病组大鼠CRA的血流速度较对照组显著降低(P<0.05),而阻力指数则显著增高(P<0.05),搏动指数高于对照组,但尚未有显著意义。3种亚型NOS在糖尿病与正常对照组视网膜中表达部位一致;但与正常对照组比较,iNOS免疫反应的强度在糖尿病大鼠视网膜中的内核层显著增强,而eNOS与nNOS的免疫反应强度则未见显著变化。结论在糖尿病早期,大鼠视网膜已开始出现血流灌注不良,此时NOS亚型中iNOS在视网膜中的表达上调可能与之相关。

The relation between expressions of nitric oxide synthase isoforms and change of retinal blood flow in early diabetic rats

·AIM:To determine whether the expression of the three isoforms of NOS in the retina is associated with the regulation of retinal blood flow at the early stage of diabetes.·METHODS: Wistar rats were divided into Control Group (n =10) and Streptozotocin-induced Diabetic Group (n =10) at random.Retinal blood flow was measured using color Doppler sonography represented as circulatory parameters in central retinal artery (CRA).Protein expression of eNOS,nNOS and iNOS in rat retina was examined through immunohistochemical ana- lyses.·RESULTS:The diabetic rats were maintained for 8wk while diabetic retinopathy was not found,but circulatory parameters of CRA had changed to abnormal.Compared with Control Group,the velocity of CRA in diabetic rats decreased significantly, but resistive index increased,and significantly,and pulsitive index was greater though without significance.The locations of the three isoforms of NOS were the same in the rat retina of both groups.In diabetic retina,iNOS immunoreactivity increased,but eNOS and nNOS immunoreactivity maintained unchanged in comparison with that in the control samples.·CONCLUSION:It is suggested that iNOS up-regulation in diabetic retina is correlated with the abnormal change of the retinal blood flow at the early stage of diabetes.