Protective Effect Of Quercetin On Retina In Oxidative Injury Mice

Objective:C57BL/6 mice were used as the research object.40 mice were made into dry AMD model by feeding a high-fat diet combined with hydroquinone,which mainly performed retinal oxide damage,and evaluate whether the model is successful by transmission electron microscopy;To observe the effect of quercetin in the regulation on Nrf2/ARE signal Channel and downstream II phase detoxification enzyme and antioxidant enzymes,to confirme the protective effect of quercetin on the retina of oxidized injured mice,and clarify the mechanism.Methods:Mice were randomized for normal control group,model group,quercetin group.According to different doses,quercetin group were consisted of low dose group(LQ,100mglkg/d),middle dose group(MD,200mg/kg/d,)and high dose group(HD,400mg/kg/d).The mice of normal control group were fed normal diet for 6 months;The mice of model group were fed a high-fat diet combined with hydroquinone 3 months;The mice of quercetin group were fed a high-fat diet combined with hydroquinone 3 months,and then given by gavage of quercetin for 3 months in different doses.The outer layer of the retina and the choroid were observed by transmission electron microscopy(TEM),the thickness of Bruch membrane(BrM)and the subRPE depodsits were examined.The activities of SOD,GSH-Px,CAT and the level of ROS and MDA in serum w.ere determined by colorimetry;The transcription and expression of Nrf2,HO-1,NQO-1 and GCL in the retina of normal animals and model animals were detected by real-time PCR and western blot.Results:The mice retina had severe oxidative damage in model group which feeding a high-fat diet combined with hydroquinone.It could be seen a large number of lipid subRPE deposits,thickened BrM by TEM in the outer retina and the choroid.It was similar to the typical pathological changes of AMD,successful simulation of dry AMD animal model.Compared with the normal control group,the activity of SOD,GSH-Px and CAT in the model group decreased significantly,and the contents of ROS and MDA increased;Compared with the model group,the activities of SOD,GSH-Px and CAT in the quercetin-treated group were significantly increased,and the contents of ROS and MDA were decreased.Western blot results showed that:In the normal control group,the expression of Nrf2 protein in the cytoplasm was higher than that in the nucleus,In the model control group,the expression of Nrf2 protein in the nucleus was higher than that in the cytoplasm,indicating that the Nrf2 protein was transferred from the cytoplasm into the nucleus when oxidative stress occurred.In the cytoplasm,the expression of Nrf2 in the quercetin group was higher than that in the model group.In the nucleus,the expression of Nrf2 in the high dose group was lower than that in the model group.The expression of N-phase metabolizing enzymes such as HO-1,NQO-1 and GCL was consistent with the expression of Nrf2 in the nucleus,that is,the high dose group was lower than the model group.PCR results showed that the expression of Nrf2,HO-1,NQO-1 and GCL in the quercetin-treated group was lower than that in the model group.Conclusion:High fat diet + hydroquinone feeding,can successfully manufacture oxidative damage mouse retina model,by observing RPE pathological changes,subRPE deposits and Bruch membrane thickness,proved that the modeling method can successfully simulate the dry AMD animal model.Quercetin can increase the activity of antioxidant enzymes in serum of oxidized injured mice and decrease the content of total active oxygen(ROS)and malondialdehyde(MDA)in serum,and thus exert antioxidant stress and show dose-dependent;Quercetin can directly against the body of a high degree of oxidative stress,relieve retinal tissue damage caused by oxidative stress,thereby protecting the retina,delay the further development of AMD.