Rho-kinase Inhibitor Ameliorates Lipopolysaccharide-induced Kidney Injury by Inhibiting Toll-like Receptor 4 and Nuclear Factor-κB Signaling Pathway
10.12007/j.issn.02584646.2018.01.001
- VernacularTitle: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
- Author:
Renyu DING
1
;
Dongmei ZHAO
;
Ziwei HU
;
Liang WANG
;
Xin LI
;
Yini SUN
;
Zhidan ZHANG
;
Xiaochun MA
Author Information
1. 中国医科大学附属第一医院重症医学科
- Keywords:
Rho kinase;
lipopolysaccharide;
acute kidney injury;
Toll-like receptor 4;
nuclear factor-κB
- From:
Journal of China Medical University
2018;47(1):1-5
- CountryChina
- Language:Chinese
-
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.
