Hydrogen sulfide reduce renal ischemia/reperfusion injury by NOD-like receptor pathway / 中华肾脏病杂志

ABSTRACT

Objective To investigate whether the nod-like receptor (NLR) pathway is involved in protection of hydrogen sulfide (H2S) preconditioning during renal ischemia reperfusion.Methods Male Wistar rats were randomly divided into 3 groupssham operation (Sham) group,renal ischemia/ reperfusion (I/R) group subjected to occlusion of left renal pedicle for 45 min then reperfusion for 24 hours,and sodium hydrosulfide (NaHS) preconditioning group with continuous infusion of NaHS (300 nmol/min) by left renal artery for 15 min before I/R treatment.Renal injuries were evaluated by HE staining.The protein levels of NOD1,NOD2,nuclear NF-κB P65 and caspase-1 were analyzed by Western blot assay.The protein level of MCP-1 and IL-1β expressions was determined by immunohistochemical staining assay.Cell apoptosis were evaluated by Tunel staining assay.Results In I/R group,the renal NOD1 and NOD2 protein expressions were upregulated.Moreover,the nuclear NF-κB P65 expression was also elevated with an increase in its target genes-MCP-1 and IL-1β (All P ＜ 0.01).HE staining revealed the existence of acute tubular necrosis in I/R kidney.TUNEL staining revealed more apoptotic cells in risk zone with the activation of caspase-1 of I/R-treated kidney(P ＜0.01).NaHS preconditioning reversed I/R-induced increase in the expression of NOD1 and NOD2(P ＜0.05).NaHS preconditioning also reduced I/R-induced activation of NF-κB P65 (P ＜ 0.05) and upregulation of MCP-1 and IL-1β (P ＜ 0.01).Moreover,NaHS preconditioning attenuated inflammation,repressed caspase-1 activation and reduced apoptotic cells after I/R.Conclusion Hydrogen sulfide preconditioning can alleviate renal ischemia/reperfusion injury by Nod-like receptor dependent on inflammatory pathway.