Hydrogen Sulfide Upregulates The Nrf2/HO-1 Pathway To Attenuate Ischemia-reperfusion Injury In The Rat Kidney

Objective:To investigate whether hydrogen sulfide（H₂S）can play a protective role in ischemic acute kidney injury by upregulating the Nrf2/HO-1 signaling pathway and inhibiting oxidative stress in a state of renal ischemia-reperfusion.Methods:Twenty-four male SD rats were divided by random method into sham-operated group（Sham group）,renal ischemia-reperfusion（I/R）group and I/R+Na HS group,with 8 rats in each group;pretreatment:the rats were anesthetized with 10%chloral hydrate（0.3ml/100g）by intraperitoneal injection,a median abdominal incision was selected,the layers of tissues were incised layer by layer,the abdominal cavity and both renal arteries were exposed,the tissues around the renal hilum were separated In the I/R+Na HS group,the left renal artery was cannulated after exposure of the left renal artery,and Na HS,a hydrogen sulfide donor,was administered continuously at 300 nmol/min for 10 min,and an equal volume of saline was injected into the left renal artery in the I/R and Sham groups.After 24 h,kidney tissues and blood specimens were collected from each group.The expression of Nrf2 and its downstream target,HO-1,was detected by western blot;the expression of reactive oxygen species（ROS）was observed by fluorescence microscopy using ROS fluorescent probe and DHE staining;the superoxide dismutase（SOD）activity and malondialdehyde（MDA）content of kidney tissues were detected by colorimetric method;the apoptosis of kidney tissues was detected by TUNEL method;and the apoptosis of kidney tissues was observed by HE staining.The histopathological changes in the kidney were observed by HE staining;serum creatinine（Scr）and urea nitrogen（BUN）concentrations were measured by colorimetric method.Results:（1）Effect of H₂S on Nrf2 and HO-1 Expression in I/R Rats The expression levels of renal tubule epithelial cells in the I/R group were higher than those in the Sham group（P（27）0.05）,and the expression levels of Nrf2 and HO-1 proteins in the I/R+Na HS group were also significantly increased（P（27）0.05）,which was statistically significant compared with the I/R group.（2）Effects of H₂S on ROS expression and MDA and SOD in I/R injured rats Compared with the Sham group,renal tissue ROS expression increased（P（27）0.01）,and SOD activity decreased、MDA content increased（P（27）0.01）;compared with the I/R group,the I/R+Na HS group showed increased ROS expression was increased（P（27）0.01）and renal tissue SOD activity was increased and MDA content was decreased（P（27）0.01）compared with the I/R group,with statistically significant differences.（3）Effect of H₂S on renal histomorphology and apoptosis in the kidney of I/R rats Compared with the Sham group,the I/R group showed increased kidney tissue damage（P（27）0.01）and significantly more apoptotic cells（P（27）0.05）;compared with the I/R group,the I/R+Na HS group showed significantly less kidney tissue damage（P（27）0.01）and apoptotic cells were reduced in the I/R+Na HS group compared with the I/R group（P（27）0.05）,and the differences were statistically significant.（4）Effect of H₂S on Scr and BUN expression in I/R-injured rats Serum Scr and BUN levels were increased in the I/R group compared to the Sham group（P（27）0.05）,and decreased in the I/R+Na HS group compared to the I/R group（P（27）0.05）,with statistically significant differences.Conclusion:（1）H₂S has a protective effect on renal function after renal ischemia and reperfusion in rats,which can reduce renal oxidative stress damage.（2）The Nrf2/HO-1 signaling pathway is involved in renal ischemia and reperfusion injury in rats.（3）H₂S can inhibit oxidative stress by upregulating the Nrf2/HO-1 signaling pathway and play a protective role in ischemic acute kidney injury.