Effects of glibenclamide on H2O2-induced edema of hypoxic cardiomyocytes,the SUR1-TRPM4 channel and expression level of AQP4
Objective To investigate the effects of glibenclamide on H2O2-induced edema of hypoxic cardiomyocytes,the sulfonylurea receptor 1-transient receptor potential melastatin 4(Sur1-Trpm4)channel and expression level of aquaporin-4(AQP4).Methods The rat cardiac cell line H9C2 was induced with blank control,H2O2+low-dose glibenclamide,H2O2+high-dose glibenclamide,and H2O2+high-dose glibenclamide+CIM2016(SUR1-TRPM4 channel activator).Cell survival and ultrastructural changes in cell edema were detected by MTT assay and transmission electron microscopy(TEM).Contents of malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)were measured by commercial kits.Quantitative real-time polymerase chain reaction(QRT-PCR)was applied to detect the mRNA levels of SUR1,TRPM4,and AQP4.Western blot was applied to detect the protein levels of SUR1,TRPM4,AQP4,BAX,and BCL-2 proteins in cells.Results Compared with those of the control group,H2O2-induced H9C2 cells were greatly swollen in volume,with significantly lower survival rate,SOD and CAT activities,and protein level of Bcl-2,but higher MDA content,mRNA Levels of SUR1,TRPM4 and AQP4,and protein levels of SUR1,TRPM4,AQP4 and Bax(P＜0.05).Compared with those induced with H2O2,H9C2 cells induced with H2O2+low-dose/high-dose glibenclamide had alleviated volume swelling,significantly higher survival rate,SOD and CAT activities,and protein level of Bcl-2,but lower MDA content,mRNA Levels of SUR1,TRPM4 and AQP4,and protein levels of SUR1,TRPM4,AQP4 and Bax(P＜0.05).CIM2016 partially reversed the role of glibenclamide in alleviating H2O2-induced swelling of H9C2 cells(P＜0.05).Conclusion Glibenclamide can alleviate H2O2-induced edema of hypoxic cardiomyocytes,increase cell survival rate,and inhibit the SUR1-TRPM4 channel and expression level of AQP4.
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