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目的 探讨Rho激酶抑制剂对内毒素血症小鼠肾损伤的影响及其分子生物学机制.方法 将成年雄性C57BL/6小鼠随机分成对照组、脂多糖(LPS)组、LPS+Y-27632组,每组8只.采用LPS(30 mg/kg)腹腔内注射建立内毒素血症小鼠模型.造模前18 h和1 h分别予以Rho激酶特异性抑制剂Y-27632或等量生理盐水腹腔注射,造模后8 h处死小鼠,留取血清及肾组织做进一步分析.结果 Rho激酶抑制剂Y-27632预处理明显减轻了LPS诱导的急性肾损伤;Y-27632能够显著降低内毒素血症小鼠肾脏炎性细胞因子(肿瘤坏死因子α和白细胞介素1β)的表达,抑制肾脏caspase-3蛋白的表达;Y-27632预处理显著下调内毒素血症小鼠肾脏Toll样受体4(TLR4)蛋白表达及核因子κB(NF-κB)p65磷酸化水平.结论 Rho激酶抑制剂可能通过抑制TLR4和NF-κB信号通路降低内毒素血症小鼠肾脏的炎症反应,缓解LPS诱导的急性肾损伤.“,”Objective To explore whether Rho kinase inhibitor protects endotoxemia mice from kidney injury,and to investigate the mechanism underlying this effect. Methods Adult male C57BL/6 mice were randomly divided into three groups (n = 8 for each group): control,lipopolysaccharide (LPS),and LPS+ Y-27632 (Rho kinase inhibitor). For induction of acute kidney injury,mice were administered 30 mg/kg LPS intraperitoneally. Y-27632 (10 mg/kg body weight) was injected intraperitoneally 18 h and 1 h before injection of LPS,and an equal volume of sterile saline was administered at the corresponding time point in each group. The mice were killed 8 h after LPS administration. Blood samples and kidney tissues were taken and preserved for subsequent analysis. Results Pretreatment with Y-27632 significantly attenuated LPS-induced kidney injury;pretreatment with Y-27632 markedly reduced renal expression of inflammatory cytokines (TNF-α and IL-1β) in endotoxemia mouse,and also significantly inhibited LPS-induced caspase-3 expression in the kidney; and Y-27632 pretreatment dramatically reduced TLR4 protein expression and NF-κBp65 phosphorylation in kidney tissues of endotoxemia mouse. Conclusion Rho kinase inhibitor may inhibit TLR4 and NF-κB signaling pathway to reduce the inflammatory response in the kidneys of endotoxemia mice and alleviate acute renal injury induced by LPS.