解毒祛瘀滋阴方对红斑狼疮鼠CD4+T细胞DNA甲基化调控的影响

项目名称： 解毒祛瘀滋阴方对红斑狼疮鼠CD4+T细胞DNA甲基化调控的影响

项目编号： No.81202673

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 陈红波

作者单位： 浙江中医药大学

项目金额： 24万元

中文摘要： 系统性红斑狼疮（SLE）是一种多系统损害、病程长、预后差的自身免疫性疾病。DNA甲基化调控是表观遗传学的重要调节方式，SLE患者DNA甲基化调节基因（Gadd45a、DNMT1）表达异常，导致CD4+T细胞基因组DNA"低甲基化"，诱导SLE发病或加重。前期研究证实解毒祛瘀滋阴方可缓解SLE病情，提高生存质量。本项目将在MRL/lpr狼疮鼠基础上（体内和体外），通过HPLC法检测该方对狼疮鼠CD4+T细胞基因组DNA甲基化水平的影响，Real-time PCR法和Western-blot法检测其对上游甲基化调节基因（Gadd45a、DNMT1）表达水平和下游甲基化敏感基因（CD70、PP2Ac、IL-10）表达水平的影响，为"解毒祛瘀滋阴方治疗SLE的DNA甲基化调控假说"提供理论依据，进一步完善其治疗SLE的作用机制，有助于其临床推广应用。

中文关键词： 系统性红斑狼疮；解毒祛瘀滋阴方；DNA甲基化；糖皮质激素受体；青蒿素

英文摘要： Systemic lupus erythematosus(SLE) is an autoimmune disease with multi-systemic organs injury, long period, and bad prognosis. DNA methylation regulation is one important regualtion of epigenetics, abnormal expression of DNA methylation regulation gene（Gadd45a and DNMT1）can induce low DNA methylation of global genome in CD4+ T cells,which will result in SLE onset or aggravation. Our previous studies confirm that Jieduquyuziyin decoction can obviously lighten SLE disease activity and improve patients' life quality. Based on MRL/lpr rats in this study, after detection of DNA methylation level of global genome of CD4+ T cells through HPLC, gene expression level of upstream methylation regulating gene（Gadd45a and DNMT1）and downstream methylation sensitive gene (CD70, PP2Acα and IL-10) were detected through Real-time PCR and Western-blot, we hope supply the hypothesis of DNA methylation regulaiton of Jieduquyuziyin decoction with theory support, broaden its clinic practice.

英文关键词： systemic lupus erythematosus；Jiedu-quyu-ziyin decoction；DNA methylation；glucocorticoid receptor；Dihydroartemisinin