中国医科大学学报2018,Vol.47Issue(1):1-5,5.DOI:10.12007/j.issn.02584646.2018.01.001
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
摘要
Abstract
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.关键词
Rho激酶/脂多糖/肾损伤/Toll样受体4/核因子κBKey words
Rho kinase/lipopolysaccharide/acute kidney injury/Toll-like receptor 4/nuclear factor-κB分类
医药卫生引用本文复制引用
丁仁彧,肇冬梅,胡紫薇,王亮,李鑫,孙旖旎,章志丹,马晓春..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[J].中国医科大学学报,2018,47(1):1-5,5.基金项目
国家自然科学基金青年项目(81201484) (81201484)
辽宁省自然科学基金(201602819) (201602819)