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

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

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,200 mg/kg)亚组和溶剂对照亚组。采用右肾切除+左肾肾蒂夹闭25min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(200mg/kg)灌胃抑制HSP27的表达。再灌注后24h,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caspase-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。

Objective To explore the effect of heat shock protein-27 （HSP27） in lipopolysaccharide （LPS）-induced renoprotection against ischemia-reperfusion （IR） injury in mice. Methods Male C57BL/6 mice were used for establishing renal IR injury model and the animals were divided into 4 groups： sham group, LPS＋sham group, IR group, and LPS＋IR group; each group was further divided into quercetin （200 mg/kg） subgroup and vehicle control subgroup. Renal IR model was established by right nephrectomy ＋ clamping the left renal pedicle for 25 min. Mice were intraperitoneally injected with LPS （3 mg/kg body weight） 3 days prior to renal IR, and the expression of HSP27 was inhibited by quercetin （200 mg/kg）, an inhibitor of HSP27 synthesis. 24 h after reperfusion, the extent of IR injury was evaluated by serum creatinine （Cr） and blood urea nitrogen （BUN） levels in abdominal aorta, and the degree of inflammatory reaction, expression of HSP27 protein and activity of apoptosis protein caspase-3 were evaluated in the left kidney. Results LPS pretreatment significantly reduced the levels of Cr and BUN in the serum, improved the expression level of HSP27, and reduced the degree of renal IR injury after renal IR （P〈0.05）. It was found that quercetin significantly inhibited the expression of HSP27 in the kidney （P〈0.05）. Quercetin could significantly weaken the alleviating effect of LPS on renal IR by elevating Cr and BUN levels and causing more severe inflammation reaction （P〈0.05）. In addition, LPS significantly reduced the activity of caspase-3 after renal IR, which could be significantly weakened by quercetin. Conclusion LPS pretreatment can relieve the renal IR injury in mice by up-regulating the expression of HSP27.