还原型谷胱甘肽调控Nrf2/iNOS信号对DR大鼠视网膜的保护机制

目的 探讨还原型谷胱甘肽调控Nrf2/iNOS信号对DR大鼠视网膜的保护机制。方法 选取48只SD大鼠，随机分成健康组、病变组、他汀组、甘肽组，每组均为12只大鼠，除健康组外其余组别均建立糖尿病视网膜病变大鼠模型，建模成功后健康组与病变组不进行用药， 他汀组大鼠给予辛伐他汀灌胃，甘肽组大鼠采用还原型谷胱甘肽干预，各组大鼠连续干预14 d，分别检测各组大鼠病理组织HE染色、氧化应激指标，Nrf2、HO-1及NO、iNOS蛋白表达水平、Nrf2、HO-1mRNA表达。结果 HE染色结果健康组大鼠视网膜细胞排列紧密，表面光滑平整；病变组细胞排列不规则，表面不光滑；他汀组和甘肽组细胞排列较规则，病变明显改善。与健康组比较，病变组ROS、MDA、NO、iNOS表达水平明显升高，SOD、GSH-Px水平降低（P<0.05）；与病变组比较，他汀组和甘肽组ROS、MDA、NO、iNOS表达水平降低，SOD、GSH-Px水平升高（P<0.05）；与他汀组比较，甘肽组ROS、MDA、NO、iNOS表达水平降低明显，SOD、GSH-Px水平明显升高（P<0.05）；与健康组比较，病变组Nrf2、HO-1、Nrf2mRNA、HO-1mRNA水平降低（P<0.05）；与病变组比较，他汀组和甘肽组Nrf2、HO-1、Nrf2mRNA、HO-1mRNA水平明显升高（P<0.05）；与他汀组比较，甘肽组Nrf2、HO-1、Nrf2mRNA、HO-1mRNA水平上升明显（P<0.05）。结论 还原型谷胱甘肽可以调控Nrf2/iNOS信号通路，改善氧化应激反应，对糖尿病视网膜病变其保护作用。

The protective mechanism of reduced glutathione regulating Nrf2/iNOS signal on the retina of DR rats

Objective To explore the protective mechanism of prototype glutathione regulating Nrf2/iNOS signal on the retina of DR rats.Methods 48 SD rats (half male and half female) were randomly divided into four groups: healthy group, pathological group, tatin group and glycine group, with 12 rats in each group.Except for the normal group, all the other groups were established diabetic retinopathy rat models. After successful modeling, the normal group and the model group were not given medication, and the rats in the statin group were given simvastatin intragastric administration.The rats in the peptide group were treated with prototype glutathione for 14 consecutive days.He staining, oxidative stress index, protein expression levels of Nrf2, HO-1, NO and iNOS, mRNA expression levels of Nrf2 and HO-1 were detected in pathological tissues of rats in each group.Results HHE staining results showed that retinal cells in healthy group were closely arranged and the surface was smooth and smooth. The cells in the pathological group were irregular and the surface was not smooth.The cell arrangement of the statin group and the glycine group was more regular, and the pathological changes were significantly improved. Compared with the healthy group, the expression levels of ROS, MDA, NO, iNOS and SOD and GSH-Px in the diseased group were significantly increased, while the levels of SOD and GSH-Px were decreased (P<0.05).Compared with the diseased group, the expression levels of ROS, MDA, NO and iNOS in the statatin group and the glycine group were decreased, while the levels of SOD and GSH-Px were increased (P<0.05).Compared with the statine group, the expression levels of ROS, MDA, NO and iNOS in the glycine group were significantly decreased, while the levels of SOD and GSH-Px were significantly increased (P<0.05).Compared with the healthy group, the mrna levels of Nrf2, HO-1, Nrf2 and HO-1 in the pathological group were decreased (P<0.05).Compared with the lesion group, the mrna levels of Nrf2, HO-1, Nrf2 and HO-1 in the statine group and the glycine group were significantly increased (P<0.05).Compared with the statine group, the mrna levels of Nrf2, HO-1, Nrf2 and HO-1 in glycine group were significantly increased (P<0.05).Conclusions Prototype glutathione can regulate Nrf2/iNOS signaling pathway, improve oxidative stress response, and protect diabetic retinopathy.