脂多糖通过上调热休克蛋白27的表达减轻小鼠肾缺血再灌注损伤

目的 探讨热休克蛋白27 (heat shock protein-27,HSP27)在脂多糖(lipopolysaccharide,LPS)减轻小鼠肾缺血再灌注(ischemia-reperfusion,IR)损伤中的作用.方法 雄性C57BL/6小鼠随机分为4组:假手术组、LPS+假手术组、肾IR组和LPS+肾IR组,每组又分为槲皮素(quercetin,200mg/kg)亚组和溶剂对照亚组.采用右肾切除+左肾肾蒂夹闭25 min后再灌注建立肾IR模型,在肾IR前3d腹腔注射LPS(3mg/kg)进行预处理,采用槲皮素(200 mg/kg)灌胃抑制HSP27的表达.再灌注后24 h,各组小鼠经腹主动脉采血检测血清肌酐(Cr)、尿素氮(BUN)水平评估肾IR损伤模型,取左肾评估炎症反应程度、HSP27蛋白表达水平及凋亡相关蛋白easpase-3的活性.结果 LPS预处理可明显降低肾IR后的血清Cr、BUN水平,并减少肾小管损伤程度,同时能提高肾内HSP27的表达水平(P＜0.05);槲皮素能明显抑制肾内HSP27的表达水平,且能明显削弱LPS预处理对肾脏IR的减轻作用,包括升高Cr、BUN水平和造成更严重的炎症反应(P＜0.05).另外,LPS能明显降低肾脏IR后肾内caspase-3的活性,但槲皮素能明显削弱这种作用(P＜0.05).结论 LPS通过上调HSP27的表达减轻小鼠肾脏IR损伤.

Lipopolysaccharide protects kidney ischemia-reperfusion injury by up-regulating heat shock protein-27 in mice

Objective To explore the role of heat shock protein-27 (HSP27) in lipopolysaccharide (LPS)-induced renoprotection against ischemia-reperfusion injury. Methods Male C57BL/6 mice were used for renal ischemia-reperfusion injury model and divided into 4 groups: sham group, sham+LPS group, IR group, and IR+LPS group, each group was further divided into 2 subgroups according to quercetin or vehicle was given. Renal IR model were established by right nephrectomy + left renal pedicle clamping for 25 min + reperfusion. Mice were treated intraperitoneally with lipopolysaccharide (LPS, 3 mg/kg body weight) 3 days prior to renal ischemia. HSP27 were inhibited by Quercetin, an inhibitor of HSP27 synthesis.The extent of IR injury was evaluated by serum Cr and BUN levels, pro-inflammatory cytokines and apoptosis-related protein (Caspase-3). Results We found LPS pretreatment stimulated renal up-regulation of HSP27 and reduced renal IR injury proven by less renal dysfunction and inflammation (P<0.05). It was observed that inhibition of Hsp27 synthesis by Quercetin abolished LPS-induced renoprotective effects, proved by elevated levels of Cr, BUN, inflammatory reaction and Caspase-3 activity (P<0.05). Conclusion LPS pretreatment protects mice against kidney IR injury and leads to up-regulation of HSP27. Inhibition of HSP27 abolishes LPS-induced renoprotection against IR injury.