Rho激酶抑制剂通过抑制Toll样受体4和核因子κB信号通路缓解脂多糖诱导的肾损伤  

Rho-kinase Inhibitor Ameliorates Lipopolysaccharide-induced Kidney Injury by Inhibiting Toll-like Receptor 4 and Nuclear Factor-κB Signaling Pathway

作　　者：丁仁彧[1] 肇冬梅[1] 胡紫薇[1] 王亮[1] 李鑫[1] 孙旖旎[1] 章志丹[1] 马晓春[1] 

机构地区：[1]中国医科大学附属第一医院重症医学科,沈阳110001

出　　处：《中国医科大学学报》2018年第1期1-5,共5页Journal of China Medical University

基　　金：国家自然科学基金青年项目(81201484);辽宁省自然科学基金(201602819)

摘　　要：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 admin- istered 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 inflamma- tory eytokines （ TNF-oL and IL-1 ） in endotoxemia mouse, and also significantly inhibited LPS-induced caspase-3 expression in the kid- ney ; and Y-27632 pretreatment dramatically reduced TLR4 protein expression and NF-KBp65 phosphorylation in kidney tissues of endo- toxemia mouse. Conclusion Rho kinase inhibitor may inhibit TLR4 and NF- K B signaling pathway to reduce the inflammatory response in the kidneys of endotoxemia mice and alleviate acute renal iniurv induced by LPS.

关 键 词：RHO激酶 脂多糖 肾损伤 TOLL样受体4 核因子KB 

分 类 号：R692.5[医药卫生—泌尿科学]