慢性移植物抗宿主病狼疮小鼠模型肾组织细胞凋亡及Th1/Th2细胞因子的研究  

Study on apoptosis and Th1/Th2 of the lupus nephritis murine models of chronic graft-versus-host disease

作　　者：任文英[1] 陈香美[2] 王新高[3] 邱全瑛[4] 陈扬荣[5] 师锁柱[2] 王兆霞[2] 尹忠[2] 

机构地区：[1]福建省人民医院肾内科 [2]解放军总医院肾病中心 [3]北京天坛医院神经内科 [4]北京中医药大学免疫学教研室 [5]福建中医学院办公室

出　　处：《中华风湿病学杂志》2004年第11期644-648,i001,共6页Chinese Journal of Rheumatology

基　　金：国家自然科学基金重点资助项目(39930230)

摘　　要：目的研究慢性移植物抗宿主病(cGVHD)狼疮样小鼠模型肾组织细胞凋亡及Th1/Th2细胞因子的改变。方法20只B6D2F1代杂交鼠,随机分为模型组(10只)及对照组(10只),12周后处死。采用原位末端标记法(TUNEL)染色观察肾组织细胞凋亡;免疫组织化学、Westernblot和反转录-聚合酶链反应(RT-PCR)技术检测Fas、FasL基因转录及蛋白表达情况。结果TUNEL法结果显示模型组肾组织细胞凋亡较对照组增多。免疫组织化学提示:各组均有Fas、FasL表达,正常对照组有极少量Fas表达,表达部位在肾小球系膜细胞;FasL表达部位在近端肾小管上皮细胞。聚合酶链反应(PCR)结果:模型组较正常对照组FasmRNA表达增高。模型组较正常对照组FasLmRNA表达差异无显著性。正常对照组干扰素(IFN)-γ和白细胞介素(IL)-4阳性细胞极少;模型组肾组织血管周围浸润的炎性细胞中可见IFN-γ和IL-4阳性细胞,且IL-4阳性细胞明显高于IFN-γ,提示Th2细胞表达占优势。模型组比正常对照组INF-γ和IL-4阳性细胞明显升高,RT-PCR结果显示:模型组IFN-γ与正常对照组比较差异无显著性;模型组IL-4较正常对照组显著升高。结论cGVHD狼疮样小鼠模型肾组织细胞凋亡异常及Th1/Th2细胞因子失衡,在狼疮肾炎(LN)的发病中起重要作用。Objective To study apoptosis and Th1/Th2 of the lupus nephritis murine models with chronic graft-versus-host disease (cGVHD). Method Twenty female murine were randomly divided into two groups, model group(10) and control group(10). Twelve weeks later,all the mice were killed. Immunohistochemistry and western blot were used to detect the level of Fas, FasL. The transcription of Fas, FasL mRNA in kidney were detected by RT-PCR, apoptosis was observed by TUNEL assay. The serum level of IL-2, TNF-α, IL-6 were detected by radioimmunoassay, the transcription of IL-4, IFN-γ mRNA in kidney were examined by RT-PCR. Results The expression of Fas was increased in model group than in control group. The protein and mRNA level of FasL was observed in control group, which showed no significant difference. The expression of IFN-γ was increased more than IL-4 in model group. The mRNA level of IFN-γ was not changed. The mRNA level of IL-4 was increased in model group. Conclusion The abnormal apoptosis and imbalance of Th1/Th2 in kidney of murine lupus nephritis model of chronic graft-versus-host disease plays an important role in the pathogenesis of lupus nephritis (LN).

关 键 词：对照组 正常 肾组织 细胞凋亡 阳性细胞 慢性移植物抗宿主病 TH1/TH2细胞因子 模样 结论 显著性 

分 类 号：R593.242[医药卫生—内科学] R692[医药卫生—临床医学]