脂多糖诱导下急性肾功能衰竭小鼠肾脏中TOLL样受体4的表达

Expression of Toll Like Receptor 4 in Kidney of Mice with Lipopolysaccharide Induced Acute Renal Failure

目的:探讨TOLL样受体4(TLR4)在脂多糖(LPS)诱导的小鼠急性肾功能衰竭(ARF)肾脏中表达及意义。方法:建立LPS诱导的小鼠ARF模型。应用免疫组织化学SABC法、Western blot及RT-PCR法检测肾组织TLR4蛋白及mRNA的表达变化。TUNEL法检测肾脏的凋亡情况。结果:TLR4在正常组(NG)肾脏中主要分布于肾小管、管周、肾间质区,肾小球系膜区也有表达,而ARF组TLR4在上述区域的表达显著增加,以近端小管、肾间质、远端小管、肾血管等部位较明显,两组光密度值比较有明显差异(P<0.05);TLR4的表达与肾功能的改变呈正相关(r=0.91);与NG组相比,ARF组的TLR4蛋白及mRNA水平的表达显著上调,以造模24 h后最明显;TUNEL法显示凋亡小体主要出现在ARF组肾脏的近端小管及管周围,肾小球无明显变化。结论:TLR4在脂多糖诱导的小鼠ARF肾脏中有较高表达,同时在其肾近端小管及小管周围组织发现较明显的凋亡小体。二者在ARF发病中可能起重要作用。

Objective： To investigate the expression and its role of Toll like receptor 4 （TLR4） in endotoxin-acute renal failure （ARF） mice. Methods： The indotoxin-ARF model was established. Immunohistochemistry（IHC）, RT-PCR and Western blot were applied to detected the expression of TLR4 mRNA and TLR4 protein respectively. Terminal deoxynucleotidyl transferase mediated X- dUTP nick end labeling （TUNEL） was applied to monitor apoptosis of renal tissue. Results： TLR4 were principally distributed in renal tubule, peritubule and interstitium, and a weak expression on glomerular mesangial region was also detected. The level of renal TLR4 mRNA and protein expression was up-regulated in ARF group compared with normal controls, which reached the peak at 24 h in ARF group. The expression of TLR4 was positive correlated with renal function. The apoptosis bodies were detected on the renal tubule and peritubule＇in the ARF group mice. Conclusion： The expression of TLR4 in kidney of LPS-induced ARF mice was obviously upregulated and the apoptosis body was detected on renal tubule and peritubule tissue of ARF mice. Both may play a role in LPS-induced ARF.