Effect Of Sofren On The Expression Of HMGB1 And TNF-? In Kidney Tissue And Serum Of Mice With Early Renal Ischemia-reperfusion Injury

Objective This study aims to investigate the protective effect of Sofren on the expression of renal ischemia-reperfusion injury(HMGB1)and serum tumor necrosis factor-alpha(TNF-?)with early renal ischemia-reperfusion injury(RIRI)in mice.and its potential mechanism,and provide animal experimental basis for the prevention and treatment of RIRI by Sofren.Methods The male C57BL/6 mice(20-30)g were randomly divided into sham operation group(Sham),Renal ischemia-reperfusion group(RIRI),Sofren injection preventive group(RIRI+S).In RIRI+S group,Sofren injection were intraperitoneally injected for three days before modeling,and the same amount of normal salinewere injected in the Sham group and RIRI group.Induce ischaemia of the both kidneys by applying a non-traumatic microvascular clip onto the renal artery and vein.Then induced ischemia for 45 minutes,remove the artery clip allow reperfusion 24 hours.Sham group does not induce RIRI.Then collecting peripheral blood and kidney tissue to detect blood urea nitrogen(BUN),serum creatinine(SCr),and pathological-HE staining.Moreover,serum TNF-? was examined by ELISA.The protein expression levels of HMGB1,Toll-like receptor 4(TLR4)and NF-?B in renal tissue were measured by Western blot.Results 1.The model of renal ischemia-reperfusion injury(RIRI)in mice was successfully constructed.HE staining suggested that reperfusion 24 h showed the typical renal tubular pathology changes of RIRI.2.The BUN(61.66±2.57)mmol/L,SCr(185.92±14.47)?mol/L,and TNF-?(223.71±8.45)pg/mL in the RIRI group were obviously higher than that in the Sham group(P<0.05).The SCr(114.66±21.19)?mol/L,BUN(36.24±3.27)mmol/L,and TNF-?(77.60±5.04)pg/mL in the RIRI+S group were lower than the RIRI group(P<0.05).3.Compared with the Sham group,the expression levels of HMGB1(0.7808±0.0127),TLR4(0.7845±0.0231),and NF-?B(0.7404±0.0182)in kidney tissue were significantly higher in the RIRI group(P<0.05).In the RIRI+S group,the expression levels of HMGB1(0.5534±0.0247),TLR4(0.5394±0.0161),and NF-?B(0.5162±0.0192)were lower than that in the RIRI group(P<0.05).Conclusion Sofren could significantly attenuate renal ischemia reperfusion injury in mice,and protect mice against RIRI.Its mechamism may involve in down-regulating the expression of HMGB1,through the HMGB1/TLR4 signaling pathway,and reducing injury of RIRI process inflammation.