Pam3CysSK4对糖尿病小鼠肾功能及肾小管上皮细胞TLR2表达的影响

Influence of Pam3CysSK4 on Renal Function of Diabetic Mice and TLR2 Expression of Renal Tu- bular Epithelial Cells

[目的]探讨Toll样受体（Toll-like receptors，TLR）的特异激动剂Pam3CysSK4对糖尿病小鼠肾功能及肾小管上皮细胞Toll样受体2（TLR2）表达的影响。【方法】选取C57小鼠24只，随机分为正常组、糖尿病模型组（模型组）和干预组，每组8只，模型组采用链脲佐菌素（STZ）诱导建立小鼠糖尿病模型，干预组建立糖尿病小鼠模型后并给予股静脉注射PamaCysSK4，每周给予100μg，正常组小鼠给予与其他两组等量枸橼酸缓冲液注射。三组喂养8周后，收集24h尿液，检测24h尿蛋白；称小鼠体重、肾重，计算肾重／体重；检测血清肌酐（Cr），血尿素氮（BUN）、血糖及白细胞介素1（IL～1）评估肾小球硬化指数，检测肾小管上皮细胞TLR2、核转录因子一出（NF-KB）及髓样分化因子88（MyD88）、单核细胞趋化蛋白-1（MCp-1）表达水平。【结果】干预组和模型组血糖均高于正常组；干预组小鼠体重和24h尿量低于模型组，而模型组低于正常组；干预组小鼠肾重和肾重／体重高于模型组，而模型组高于正常组，其差异均有统计学意义（Pd0．05）。干预组和模型组Cr、BUN、IL-1和24尿蛋白含量、肾小球硬化指数及TLR2、NF-KB、MyD88和MCP-I均高于正常组，而干预组高于模型组，其差异均有统计学意义（P〈0．05）。【结论】高糖能够上调小鼠肾小管上皮细胞TLR2水平，激活TLR信号转导通路，促进炎症因子的释放，增加对肾脏的损伤作用。

[Objective]To study the influence of Pam3CysSK4 on renal function of diabetic mice and TLR2 expression of the renal tubular epithelial cells. [Methods]Twenty-four C57 mice were selected and randomly divided into the normal group, diabetic model group （the model group） and the intervention group, 8 rats in each group. The model group was induced by the use of streptozotocin （STZ） to establish diabetes model in mice. The diabetic mice model was established in the intervention group with intravenous injection of Pam3CysSK4, 100 μg/ week, The normal group mice was given with the same amounts of citrate buffer injection as the other two groups did . After they were fed for 8 weeks,24 h urine and 24 b urine protein were collected and evaluated, mice body and kidney were weighed and calculated , and serum creatinine （Cr）, urea nitrogen （BUN）, blood glucose and interleukin-1 （ILl） were detected to assess glomerular sclerosis index, and detection was also made on Toll like receptors（TLR2）, Nuclear Translocation factor kB （NF-kB）, myeloiddifferentiationfactor88 （MyD88） and monocyte chemotactic protein 1 （MCP-1） to find out their expression levels. [Results]The blood glucose levels of the intervention group and the model group were higher than that of the normal group. In the intervention group, the kidney weight and kidney weight / body weight were higher than that of the model group, while the model group was higher than the normal group, the difference was statistically significant （ P 〈0.05）. Of the intervention group and model group, the Cr, bun, IL-1 and 24 h urinary protein content and glomerular sclerosis index ,TLR2, NF-kB, MyD88 and MCP-1 were higher than those in normal control group, the intervention group were significantly higher than the model group, the differences were statistically significant （ P 〈0.05）.[Conclusion]High glucose can increase TLR2 level of mouse renal tubular epithelial cells, activate TLR signaling pathway, promote the release of inflammatory factors and increase the damage to the kidney.