TLR4信号转导途径在大鼠系膜增生性肾小球肾炎的作用机制探讨

目的 探讨Toll样受体4（TLR4）信号转导途径在系膜增生性肾小球肾炎（MSPGN）发病机制中的作用；同时观察来氟米特对该途径的影响及对MSPGN的干预作用.方法 48只SD雄性大鼠随机分为4组：A组：正常对照组（n=12）；B组：模型组（n=12）；C组：来氟米特2 mg·kg-1·d-1组（n=12）；D组：来氟米特5 mg· kg-1·d-1组（n=12）.各组大鼠均于实验4、8、12周末检测24h尿蛋白定量、血清胱抑素C、血肌酐水平；HE、PAS染色光镜下观察肾组织系膜增生程度；免疫组化两步法检测TLR4、NF-κB、细胞因子IL-6、TNF-α蛋白的表达情况；RT-PCR法检测TLR4、NF-κB、IL-6、TNF-α mRNA的表达情况.结果 B、C、D组大鼠24h尿蛋白定量、血清胱抑素C、血肌酐水平、肾组织系膜增生程度、TLR4、NF-κB及细胞因子IL-6、TNF-α的水平均高于A组（P＜0.05）,而C、D组的水平则明显低于B组（P＜0.05）.且与C组相比,D组上述指标明显减低（P＜0.05）.结论 MSPGN的发生可能与TLR4信号转导途径活化诱导的炎症反应有关,来氟米特可通过抑制该途径对MSPGN起干预作用.

The significance of Toll-like receptor 4 signaling pathway during rat mesangial proliferative glomerulonephritis

Objective To investigate the role of TLR4 signaling pathway in rat with mesangial proliferative glomerulonephritis,and explore the effect of leflunomide on this pathway and its intervention to mesangial proliferative glomerulonephritis.Methods A total of 48 normal male Sprague-Dawley rats were randomly divided into groups A （healthy rats）,group B （nephritis rats）,group C （nephritis rats treated with leflunomide 2 mg· kg-1 · d-1）,group D（nephritis rats treated with leflunomide 5 mg · kg-1 · d-1） with 12 rats in each group.24-hour urinary protein excretion,serum cystatin C and serum creatinine were tested in the end of 4,8 and 12 week.The proliferation of mesangial cell was estimated by HE and PAS staining of paraffin section.The expression of TLR4,NF-κB,IL-6 and TNF-α was detected by immunohistochemisty and RT-PCR.Results Compared with group A,24-hour urinary protein excretion,serum cystatin C and creatinine in groups B,C and D increased significantly （P ＜ 0.05）.The degree of mesangial proliferation and expression of TLR4,NF-κB,IL-6 and TNF-α were higher in groups B,C and D （P ＜ 0.05）,and the level in groups C and D were significantly lower than group B （P ＜ 0.05）.Compared with group C,those indicators in group D were significantly lower （P ＜ 0.05）.Conclusions The proliferation of mesangial glomerulonephritis is correlated with the inflammatory response induced by TLR4 signal transduction pathway and leflunomide can inhibit the proliferation of mesangial cell mediated by this pathway.