Toll样受体2在脂多糖诱导的急性肾损伤小鼠肾脏足细胞的表达及其意义

Expression and significance of TLR2 in podocyte of mice with the acute kidney injury

目的研究脂多糖（LPS）诱导的脓毒症性急性肾损伤（AKI）小鼠Toll样受体2（TLR2）的表达规律、分布特点并对其机制进行初步探讨。方法采用小鼠腹腔注射LPS造成脓毒症性AKI模型，将40只清洁级小鼠随机分为生理盐水（NS）对照组（20只）和LPS模型组（20只），分别测定各组血清尿素氮、肌酐及24h尿蛋白水平，HE染色观察肾组织病理变化。应用免疫组化染色法观察TLR2在两组肾脏的分布特点。应用实时荧光定量PCR（real—timequantitativePCR）法检测两组肾组织TLR2mRNA的表达水平。结果腹腔注射LPS后24h血清尿素氮、肌酐及24h尿蛋白水平较对照组明显升高，肾脏病理变化亦支持AKI模型造模成功。应用免疫组化染色法检测TLR2在NS组小鼠肾小球内皮细胞有少量表达，足细胞几乎无表达，而在LPS组肾小球内皮细胞及足细胞表达明显增多，而且实时定量PCR法显示，LPS组肾组织TLR2mRNA表达较NS组明显增高（5．52±0．21vs1．00±0．05，P〈0．01）。结论在LPS诱导的脓毒症性AKI中，肾组织TLR2表达明显上调，尤其足细胞及肾小球内皮细胞表达明显增加。TLR2信号途径在足细胞和肾小球内皮细胞的激活可能介导脓毒症性AKI的发生。

Objective To investigate the expression of Toll - like receptor 2 （ TLR2 ） in the lipopolysaccharide （LPS） - induced septic acute kidney injury （AKI） mice and the potential mechanism. Methods Using LPS - treated mice as a model of septic AKI, forty mice were randomly divided into normal control group （ n = 20）, LPS group （ n = 20）. Urinary albumin levels of 24 hours, blood urea nitrogen and creatinine were tested. The expression and distribution of TLR2 in kidney were determined by immunohistochemistry. Reverse transcriptional - polymerase chain reaction （ RT - PCR） was performed to evaluate the mRNA levels of TLR2. Results In the LPS - treated mice, urinary albumin levels increased associated with the elevation of blood urea nitrogen and creatinine levels, indicating the successful induction of septic AKI. Compared with the control group, the expression of TLR2 in podocytes and glomerular endothelial ceils of kidney significantly increased in LPS group. TLR2 mRNA expression was up - regulated in LPS group compared with the control group （5.52 ＋ 0.21 vs 1.00 ＋ 0. 05, P 〈 0. 01 ）. Conclusion LPS treatment led to an significant increase of TLR2 expression, especially in the podocytes and glomerular endothelial cells of kidney. The activation of TLR2 signal way might play an important role in the pathogenesis of septic AKI.