薯蓣皂苷激活Nrf2/HO-1通路在糖尿病视网膜病变大鼠发病机制中的作用OA

Objective To explore the effect of dioscin(Dio)on the pathogenesis of diabetic retinopathy(DR)in rats by activating the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods The rats were divided into the control(NC)group,the DR group,the low-dose Dio(Dio-L)group,the high-dose Dio(Dio-H)group,and the Dio-H+Nrf2 inhibitor(ML385)group.Except for the NC group,all other groups were induced to establish a DR rat model via intraperitoneal injections of streptozotocin.Fasting blood glucose levels and body weight of rats were measured.Hematoxylin-eosin staining was used to observe pathological changes in retinal tissue of rats;TUNEL staining was employed to detect cell apoptosis in retinal tissue of rats;assay kits were applied to measure the levels of glutathione perox-idase(GSH-Px),catalase(CAT),and malondialdehyde(MDA)in retinal tissue of rats;quantitative real-time polymerase chain reaction was performed to assess the levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,NAD(P)H:quinone oxidoreductase 1(NQO1),and glutamate-cysteine ligase catalytic subunit(GCLC)in retinal tissue of rats;and Western blot was used to determine protein levels of Nrf2 and HO-1 in retinal tissue of rats.Results In the NC group,rat retina exhibited normal morphology,with well-arranged cells and no inflammatory infiltration.Compared to the NC group,the DR group showed a significant reduction in retinal ganglion cells,accompanied by inflammatory infiltration and vacuolar edema;in addition,fasting blood glucose level,apoptosis rate,MDA,TNF-α,IL-1β,and IL-6 mRNA levels were significantly elevated(all P<0.05),while body weight,GSH-Px and CAT levels,NQO1 and GCLC mRNA levels,as well as Nrf2 and HO-1 protein levels markedly decreased(all P<0.05).In contrast to the DR group,both the Dio-L and Dio-H groups showed a significant increase in retinal ganglion cells and reduced inflammatory infiltration;furthermore,fasting blood glucose level,apoptosis rate,MDA,TNF-α,IL-1β,and IL-6 mRNA levels significantly decreased(all P<0.05),whereas body weight,GSH-Px and CAT levels,NQO1 and GCLC mRNA levels,as well as Nrf2 and HO-1 protein levels were markedly elevated(all P<0.05),with more pronounced changes in the Dio-H group.In the Dio-H+ML385 group,the trend of changes in all the above indicators was opposite to that in the Dio-H group(all P<0.05).Conclusion Dio can alleviate DR in rats by activating the Nrf2/HO-1 pathway to inhibit oxidative stress and inflammatory response.