拮抗Toll样受体4的表达对内毒素血症小鼠肾脏损伤的保护作用

Protective effect of antagonism of toll-like receptor 4 expression on renal injury in LPS-induced sepsis mice

目的观察拮抗Toll样受体4(TLR4)的表达对内毒素血症小鼠肾脏损伤的保护作用以及对细胞核因子-κB(NF-κB)p65的影响。方法采用内毒素(LPS)诱导的小鼠急性肾功能衰竭模型,并应用TLR4单克隆抗体进行干预,观察TLR4单克隆抗体对内毒素血症小鼠的肾脏组织学、血清肌酐(Cr)、尿素氮(BUN)、胱抑素C、白细胞介素(IL)-1β、IL-6水平以及肾组织中TLR4及NF-κB水平的影响。结果与模型组比较,TLR4单克隆抗体能够明显改善内毒素血症小鼠肾脏组织病理学损害;降低血清中Cr、BUN、胱抑素C、IL-1β和IL-6水平(t=7.20、7.86、9.99、8.79、3.92,P均<0.05),并且降低肾组织中TLR4及NF-κB p65水平(t=20.94、11.21,P均<0.05)。结论 TLR4单克隆抗体能够保护内毒素血症小鼠肾脏组织损伤,其作用机制可能与调节TLR4/NF-κB信号转导通路有关。

Objective To investigate the protective effect of antagonism of toll-like receptor 4（TLR4） expression on renal injury in LPS（lipopolysaccharide）-induced sepsis mice, and its influence on nuclear factor（NF）-κB p65. Methods Acute kidney injury was induced by LPS. Anti-TLR4 monoclonal antibody was applied to treat the mice. The effects of TLR4 monoclonal antibody on renal histology, serum creatinine（Cr）, blood urea nitrogen（BUN）, cystatin C, interleukin（IL）-1β and IL-6 levels, and TLR4 and NF-κB protein levers in renal tissue of mice with endotoxemia were analyzed. Results The pathological changes of renal tissue were improved by blockade of TLR4 compared with model group. The serum levels of Cr, BUN, cystatin C, IL-1β and IL-6 were decreased by treatment of TLR4 monoclonal antibody compared with model group（t =7.20, 7.86, 9.99, 8.79 and 3.92, respectively; all P〈0.05）. The TLR4 and NF-κB protein levels in renal tissue were also decreased by blockade of TLR4（t = 20.94, 11.21, respectively; both P〈0.05）. Conclusions Blockade of TLR4 could protect renal injury in LPS-induced sepsis mice. The mechanism may be related to the regulation of TLR4/NF-κB signaling pathway.