ABSTRACT
Objective To observe the expression levels of kidney injury molecule-1(KIM-1) in renal tissues of ischemia-reperfusion rats,and to explore the value in the diagnosis of acute kidney injury.Methods Rats were randomly divided into two groups,control(CON) group (n=64) and acute kidney ischemia reperfusion injury (AIKI) group (n=64).Rats were sacrificed following reperfusion 2h,6h,24h,48h,72h,1 week (w),2 w,and 4 w.The changes of morphology were checked on HE staining sections under light microscope.The extent of tubulointerstitial injury was determined by Sayhan classification.The distribution and expression of KIM-1 in renal tissue were observed by immunohistochemistry and Western blotting.Serum samples were collected and serum creatinine measurement was performed at different reperfusion time points.Results (1) Compared with the CON group,the renal tubulointerstitial injury scores of AIKI group were significantly higher at all times after reperfusion (P<0.01).(2) The expression of KIM-1 was consistent with the tubulointerstitial injury.The positive correlation between KIM-1 and the tubulointerstitial injury scores was significant(r=0.887,P=0.003).(3) Compared with the CON group,serum creatinine in AIKI group was significant higher at 2h,6h,24h,48h,72h after reperfusion (P<0.05).Serum creatinine had no correlation with the damage of renal tubulointerstitial.Conclusion The expression of KIM-1 increases significantly in renal ischemia reperfusion injury,and it is consistent with the tubulointerstitial injury.Compared with serum creatinine,KIM-1 may be a more accurate biomarker of renal damage.
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 groups:sham 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.