Effect Of Estrogen On Cx43 Expression In Renal Tubular Epithelial Cells After Renal Ischemia-reperfusion Injury In Rats

Object:To investigate whether estrogen（E2）attenuates renal ischemia-reperfusion（I/R）injury by regulating Cx43 expression in renal tubular epithelial cells.Methods:All female Sprague-Dawley（SD）rats were treated with ovariectomized（OVX）（each rat was anesthetized by injection of 3%sodium pentobarbital（50 mg/kg）from the left lower abdomen,and after successful anesthesia,the female ovaries were removed bilaterally）and then divided into OVX group,OVX+sham-operated group,OVX+I/R group,and OVX+I/R+estrogen group using a random number table.The OVX group was no longer treated after the de-ovulation procedure.The OVX+sham surgery group underwent sham surgery after 2 weeks of recovery from the de-ovulation procedure.The OVX+I/R group was prepared for renal ischemia-reperfusion injury model after 2 weeks of recovery from de-ovalization surgery.The OVX+I/R+estrogen group received continuous estrogen（100μg/kg·d）intervention for the first 3 days of the renal ischemia-reperfusion injury model preparation.The degree of kidney tissue damage was assessed by measuring blood SCr and BUN in rats,performing HE staining of the kidney,followed by Paller score.The location and expression of Cx43 in renal tubular epithelial cells were observed by immunohistochemistry and western blotting.Results:The serum creatinine and urea nitrogen levels were significantly higher in the OVX+I/R group than in the OVX group（P<0.05）.The serum creatinine and urea nitrogen levels were significantly lower in the OVX+I/R+E₂group than in the OVX+I/R group（P<0.05）.HE staining revealed that the renal tubules in the OVX+I/R group were significantly dilated compared with the OVX group,and most of the cells were ruptured and necrotic.The Paller scores were significantly higher in the OVX+I/R group than in the OVX group（P<0.05）.Reduced tubular dilatation,cell rupture and necrosis were seen in the OVX+I/R+E₂group compared to the OVX+I/R group.The Paller score was significantly lower in the OVX+I/R+E₂group than in the OVX+I/R group（P<0.05）.The positive expression of Cx43 protein in renal tubular epithelial cells in the OVX+I/R group was found to be higher than that in the OVX group（P<0.05）by immunohistochemistry,and the positive expression of Cx43 protein in renal tubular epithelial cells in the OVX+I/R+E2 group was lower than that in the OVX+I/R group（P<0.05）.The western blotting assay showed that the Cx43 protein expression in the OVX+I/R group was significantly higher than that in the OVX group（P<0.05）.Cx43protein expression was significantly lower in the OVX+I/R+E₂group than in the OVX+I/R group（P<0.05）.Conclusion:Estrogen may attenuate renal ischemia-reperfusion injury by downregulating Cx43 expression in renal tubular epithelial cells after renal ischemia-reperfusion injury.