Toll样受体-9在肾小球肾炎进展中的作用  

Role of TLR9 in pathogenesis of glomerulonephritis

作　　者：罗萍[1] 卢雪红[1] 吴曼[1] 顾华[1] 

机构地区：[1]吉林大学第二医院肾病内科,吉林长春130041

出　　处：《吉林大学学报（医学版）》2007年第6期1005-1008,F0003,共5页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅资助课题(200505130)

摘　　要：目的:通过观察CpG-ODN对肾小球肾炎刺激后Toll样受体-9(TLR9)的变化,探讨TLR9在肾小球肾炎发生、发展中的变化及作用。方法:Wistar雄性大鼠,随机分为正常组(N组)、抗-thy1.1肾炎模型组(M组)、模型+CpG-ODN注射组(CpG组)、模型+GpC-ODN注射组(GpC组)。各组大鼠分别于用药后2、4、6和8周留取24 h尿;实验第8周留取24 h尿,心脏采血、留取肾脏后处死。用考马斯亮蓝法检测24 h尿蛋白定量;血清学方法检测血清白蛋白和肾功能;肾脏组织用于肾脏病理检查、NF-κB p65免疫组化染色,RT-PCR法检测肾脏组织内TLR9、INF-γ及IL-6 mRNA的表达。结果:TLR9在M组轻度表达,在给予CpG-ODN刺激后,TLR9、IL-6和IFN-γmRNA在肾脏表达率与M组比较均明显增加,24 h尿蛋白漏出量增多,血清白蛋白显著降低;光镜下可见病理改变明显加重,MCs弥漫性中、重度增生,部分肾小球有细胞性新月体形成,多处粘连,毛细血管襻开放受限,系膜区可见单核巨噬细胞浸润。结论:TLR9介导的趋化因子和趋化因子受体表达加重肾小球肾炎的生化及病理改变,TLR9介导的免疫反应是引起肾小球肾炎不断进展的机制之一。Objective To investigate the role of TLR9 in the glomerulonephritis through observing the changes of Toll-like receptor 9 in the glomerulo- nephritis kidney tissue with or without CpG-ODN stimulation . Methods Wistar male rats were randomly divided into normal group （N）, nephritis model group （M）, CpG-ODN group （CpG） and GpC-ODN group （GpC） . The urine samples were collected at 2, 4, 6 and 8 weeks after treatment, respectively. Blood samples were collected at the end of the last urine sample was collected, and the kidney tissue was collected, then the rats were killed. 24 h urine protein was measured by Coomassie light blue technique. Serum album and renal function were determined by serological method. The pathologic changes of kidney were observed by light microscope and NF-κB p65 expression was detected using immunohistochemystry, RT-PCR was performed to detect the expressions of TLRg, INF-γ and IL-6 mRNA. Results The expression of TLR9 was lighter in group M, and significantly increased after CpG-ODN stimulation compared with group M. Furthermore, 24 h urine protein excretion was markedly increased, serum album was markedly decreased. The histopathologic changes of kidney were more severe. The mesangial ceils （MCs） proliferated diffusifully in midrange and wide range, some of the glomeruli formatted cellularity crescent, micrangium loop was limitted, mononuclear macrophile ceils were seen in the mesangial region. Conclusion Inflammatory factors mediated by TLR9 can deteriorate the biochemical and histopathologic changes. The immunologic reaction mediated by TLR9 is one of the mechanisms for the glomerulonephtitis＇ progression.

关 键 词：TOLL样受体-9 系膜增生性肾小球肾炎 寡聚脱氧核糖核酸 

分 类 号：R-332[医药卫生] R692.31