Effects Of Hydrogen Sulfide On Oxidative Stress And Inflammation In Retinal Pigment Epithelial Cells Induced By High Glucose

Background:Diabeticretinopathyisthemostimportant manifestation of diabetic microangiopathy and the main cause of blindness worldwide.Its pathogenesis is not yet fully understood,it lacks scientific and effective prevention and treatment programs.Recent studies have found that the ROS-inflammasome pathway plays an important role in the development of diabetes.Hydrogen sulfide is the third gaseous signal molecule found after NO and CO.Studies have shown that hydrogen sulfide plays an important role in the pathophysiological processes of various system diseases and plays a wide range of biological effects.Objectives:This study was to investigate the effect of hydrogen sulfide on oxidative stress and inflammation in ARPE-19 cells induced by high glucose.Methods:ARPE-19 cells were cultured in low glucose or high glucose environment.ARPE-19 cells in high glucose environment were pretreated with NAC,NLRP3 siRNA or NaHS.Cell viability was detected by CCK-8;ROS produced in cells were detected by flow cytometry;mRNA levels of NLRP3,ASC,Caspase-1,IL-1?and IL-18 were detected by Rt-PCR;IL-1?and IL-18 protein expression was detected by ELISA.Results:Compared with the low glucose group,ARPE-19 cell activity was significantly decreased in the high glucose group,and the expression of inflammatory cytokines IL-1?and IL-18 mRNA and protein production were increased.In the high glucose environment,the NLRP3inflammasome was activated in ARPE-19 cells,the mRNA expression levels of NLRP3,ACS and caspase-1 were significantly increased.Antioxidant NAC can significantly reduce high glucose-induced ROS formation,block the activation of NLRP3 inflammasome,and inhibit the expression of inflammatory cytokines IL-1?and IL-18 mRNA and protein.Inhibition of NLRP3 gene expression also reduced intracellular expression of IL-1?and IL-18 mRNA and protein.Further studies found that hydrogen sulfide can significantly inhibit high glucose-induced ROS formation,activation of NLRP3 inflammasome and expression of IL-18 and IL-1?.Conclusion:H₂S may inhibit the high glucose-induced oxidative stress and inflammatory response in ARPE-19 cells by regulating ROS-inflammasome pathway,suggesting that H₂S may have potential protective effect in DR.