从中性粒细胞自释DNA经TLR9激活自身免疫探讨解毒祛瘀滋肾法对系统性红斑狼疮的作用机理

项目名称： 从中性粒细胞自释DNA经TLR9激活自身免疫探讨解毒祛瘀滋肾法对系统性红斑狼疮的作用机理

项目编号： No.81202628

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： 徐莉

作者单位： 浙江中医药大学

项目金额： 23万元

中文摘要： 系统性红斑狼疮(SLE)是一种累及多系统多脏器损害的自身免疫性疾病，糖皮质激素是目前临床治疗系统性红斑狼疮的主要方式，长期使用会产生很多副作用。解毒祛瘀滋肾法能显著降低SLE病情活动和减少激素用量。前期研究数据显示解毒祛瘀滋肾法对固有免疫系统的调节与糖皮质激素的作用机制并不完全相同。解毒祛瘀滋肾方可以抑制单核细胞的凋亡并增强其吞噬作用，糖皮质激素则显著诱导外周血细胞凋亡并抑制巨噬细胞的吞噬能力。 中性粒细胞过度凋亡自释DNA激活自身免疫是启动SLE发病的重要原因。我们推测解毒祛瘀滋肾法通过调节TLR9的信号通路抑制了中性粒细胞的凋亡，并增强了单核巨噬细胞的吞噬能力，从而达到增效减毒作用。在本课题中我们将MRL/lpr狼疮鼠和TLR9基因敲除小鼠进行平行比较，并进行相应的细胞学实验，探讨解毒祛瘀滋肾方对系统性红斑狼疮粒-单核细胞的TLR9信号通路调节。

中文关键词： 解毒祛瘀滋肾法;；系统性红斑狼疮；中性粒细胞；Toll 样受体9；

英文摘要： Systemic lupus erythematosus (SLE) is a kind of autoimmune diseases involving multiple organs damage.It is mainly treated with glucocorticoids,while as it is well known that long-term use of glucocorticoids is accompanied with many side-effects. The theraputic method,Jieduquyuzishen can successfully control SLE and relieve patients'dependence on glucocorticoid.Our previous research indicated that Jieduquyuzishen recipe regulating natural immune system is different from that of glucocorticoids. Jieduquyuzishen recipe inhibits peripheral white blood cell apoptosis and enhances the phagocytosis,while glucocorticoid induces lymphocyte apoptosis and inhibites macrophage phagocytosis. Activation of the immune system by apoptosis of neutrophil can cause the deterioration of SLE.We hypothesize that Jieduquyuzishen method inhibits neutrophil apoptosis and enhances macrophage phagocytosis through modulation of TLR9 signaling pathway. In this study,we compare the difference of MRL/lpr lupus mice and TLR9 knockout mice that treated with Jieduquyuzishen recipe and also for cytology test.Then we study the mechanism of Jieduquyuzishen method on regulation of TLR9 signaling pathway in granulocyte-monocytes of SLE.

英文关键词： Jieduquyuzishen prescription (JP);；systemic lupus erythematosus (SLE);；neutrophils;；toll-like receptor 9(TLR9)；