丹蒌片通过Keap1-Nrf2/HO-1信号通路缓解视网膜缺血-再灌注损伤OACSTPCD

AIM:To investigate the protective effect and mechanism of Danlou tablet on retinal ischemia-reperfusion injury(RIRI)in mice. METHODS:A total of 40 ApoE-/-mice were fed with high fat diet for 6 wk,and the RIRI model was established by anterior chamber infusion of pressurized saline.The mice were divided into control group(normal saline for 8 wk),RIRI model group(normal saline for 8 wk),and low-,medium-,and high-dose Danlou tablets groups[1,2,and 4 g/(kg·d),respectively,for 8 wk].The morphological changes of retina were observed by hematoxylin-eosin(HE)staining,retinal cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated Nick-End Labeling(TUNEL)staining.The Western-blot assay was used to detect the expression of retinal tissue sample Kelch-like ech-associated protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2),heme oxygenase 1(HO-1),and superoxide dismutase(Sod2)proteins. RESULTS:Compared with the control group,the mouse retina was atrophic with thinning thickness and increasing cell apoptosis,down-regulation of Sod2 protein expression,and up-regulation of Keap1 protein expression in the RIRI model group(all P＜0.01).Compared with the RIRI model group,the retinal thickness increased in the medium-and high-dose of Danlou tablets groups(all P＜0.01),and the cell apoptosis of retina decreased in the low-,medium-and high-dose of Danlou tablets groups(all P＜0.05).There were no significant differences in the expression of Keap1 and HO-1 proteins of mouse retina tissue in the low-dose of Danlou tablets group(P＞0.05).The expression of Sod2,Nrf2 and HO-1 proteins up regulated,and the expression of Keap1 protein down regulated in the medium-and high-dose of Danlou tablets groups(all P＜0.05). CONCLUSION:Danlou tablet can alleviate RIRI-induced atrophy and thinning of retina and retinal cell apoptosis by regulating Keap1-Nrf2/HO-1 signal pathway and reducing oxidative stress.