还原型谷胱甘肽对糖尿病大鼠视网膜病变干预研究

Activation of iNOS in the Retina of Diabetic Rat is Regulated by Glutathione

目的探讨糖尿病视网膜病变与诱导型一氧化氮合酶的表达的关系并探讨还原型谷胱甘肽对诱导型一氧化氮合酶表达的影响以及对糖尿病视网膜病变的防治作用。方法雄性SD大鼠70只随机分成对照组10只,糖尿病1、3、6月组以及还原型谷胱甘肽干预3、6月组各12只。分别留取视网膜标本,部分标本观测视网膜病理改变;部分标本采用免疫组化法测定诱导型一氧化氮合酶表达。结果视网膜病理结果显示:与正常对照组相比,糖尿病1、3、6月组视网膜病理改变逐步加重;免疫组化分析结果显示诱导型一氧化氮合酶表达在糖尿病各组均明显增强(P均<0.05),干预组较糖尿病各组均有明显改善(P均<0.05)。结论糖尿病视网膜病变早期就出现视网膜诱导型一氧化氮合酶表达增强,且随着视网膜组织病理学改变而持续活化。还原型谷胱甘肽有效抑制了诱导型一氧化氮合酶表达,从而达到视网膜保护的目的 。

Objective To investigate the expression of retina inducible isoform of nitric oxide synthase （iNOS） at different stage of Diabetic Rats and the effects of glutathione （GSH） on diabetic retinopathy. Methods and Methods：Seventy Sprague-Dawley rats were randomly divided into control group,diabetic group and glutathione treatment group. Diabetic model of rat was induced by injecting streptozotocin（STZ）. The morphology in retinal paraffin slide was observed by microscope. The expression of iNOS was detected by immunohistochemistry. Results Histopathology was detected at 3 months. The change of histopathology is severe at 6 months than at 3 months. 1 months of diabetes in rats resulted in retinal iNOS activation（ as detected by immunohistochemistry） , and iNOS remained activated at 3 and 6 months of diabetes. Glutathione inhibited elevations of iNOS expression, without ameliorating the severity of hyperglycemia. Conclusion iNOS is activated in retina in diabetes before histopathology can be seen, and remains activated for the duration when the retinopathy is developing. Glutathione might be inhibiting the development of retinopathy by inhibiting iNOS activation.