Role of the expression of heat shock protein 70 and heme oxygenase-1 in reduction of renal ischemia-reperfusion injury by iscbemic postconditioning in rats

Abstract

[ Abstract] Objective To evaluate the role of the expression of heat shock protein 70 （HSP70） and heme oxygenase-1 （HO-1） in the reduction of renal ischemia-reperfusion （I/R） injury by ischemic postconditioning in rats. Methods One hundred and forty healthy male SD rats weighing 250-280 g were randomized into 4 groups （ n = 35 each） ： sham operation group （S group） ; I/R group; ischemic postconditioning group （IPo group） ; quer- cetin （an inhibitor of HSP） ＋ ischemic postconditioning group （Q ＋ IPo group）. Renal I/R was produced by clamping bilateral renal pedicels for 45 min followed by reperfusion. In group S, bilateral kidneys were only ex- posed through a midline incision but their pedicels were not clamped. In IPo and Q ＋ IPo groups, 45 min isehemia was followed by three 10 s episodes of ischemia at 10 s intervals for reperfusion and in addition intraperitoneal quer- cetin 100 mg/kg was injected at 1 h before ischemia in group Q ＋ IPo. Blood samples from hearts were obtained at 0, 1, 3, 6, 12, 24 and 48 h of reperfusion （T0.6） and the rats were then sacrificed and kidneys removed to detect the expression of HSPT0 and HO-1 mRNA and protein in renal tissues. The blood samples obtained at T3 were used to determine serum creatinine （Cr） and urea nitrogen （BUN） concentrations and the expression of caspase-3 mR- NA. The apoptosis in the renal tissues was detected using TUNEL and apoptotic index （AI） was calculated. Microscopic examination was performed with light microscope. Results Compared with group S, the serum Cr and BUN concentrations and AI were significantly increased at T3, the expression of caspase-3 mRNA was up-regulated at T3 , and the expression of HSP70 and HO-1 mRNA and protein was up-regulated at T0-6 in the other groups （ P 〈 0.05）. Compared with group I/R, the serum Cr and BUN concentrations and AI were significantly decreased at T3, the expression of caspase-3 mRNA was down-regulated at T3, and the expression of HSP70 and HO-1 mRNA and protein was up-regulated at T1-5 in group IPo （P 〈 0.05）. Compared with group IPo, the serum Cr and BUN concentrations and AI were significantly increased at T3, the expression of caspase-3 mRNA was up-regulated at T3, and the expression of HSP70 and HO-1 mRNA and protein was down-regulated at T1-5 in group Q ＋ IPo （ P 〈 0. 05）. The microscopic examination showed that the renal I/R injury was significantly attenuated by ischemic postconditioning and the degree of injury in group IPo was similar to that in group I/R. Conclusion The expression of HSP70 and HO-1 is involved in the reduction of renal I/R injury by ischemic postconditioning in rats. Key words: HSP70 heat-shock proteins; Heme oxygenase-1; Renal; Reperfusion injury; Ischemic postconditioning