抗磷脂抗体对肾内生性补体和组织因子表达的影响在抗磷脂综合征肾病发病机制中的意义

项目名称： 抗磷脂抗体对肾内生性补体和组织因子表达的影响在抗磷脂综合征肾病发病机制中的意义

项目编号： No.81072471

项目类型： 面上项目

立项/批准年度： 2011

项目学科： 轻工业、手工业

项目作者： 杨程德

作者单位： 上海交通大学

项目金额： 10万元

中文摘要： 抗磷脂综合征肾病（APSN）近年来逐渐引起临床的重视，抗磷脂抗体（aPL）致APSN 的发病机制仍不甚清楚。aPL 是一组异质性的抗体，可以识别与凝血相关的蛋白分子。我们前瞻性的研究发现狼疮抗凝物、抗βPI 抗体和抗凝血酶抗体与狼疮性肾炎患者肾小球微血栓形成相关，且补体参与APSN 的形成。 在此基础上，我们利用纯化的APSN 患者抗βPI抗体腹腔注射入狼疮小鼠和C57小鼠，发现抗βPI可以诱发狼疮小鼠产生肾脏微血栓，而正常人IgG不能诱发狼疮小鼠产生肾脏微血栓。另一组用C57小鼠的试验显示，抗βPI抗体不能诱发C57小鼠肾脏微血栓的形成，从而揭示，抗磷脂抗体诱发肾脏微血栓的形成需要炎症的基础。通过比较分析抗βPI抗体和正常IgG处理狼疮鼠肾脏内生性补体和组织因子表达的水平，揭示抗βPI抗体可以增加小鼠肾脏内生性补体地产生，但对肾脏组织因子的表达无影响。揭示aPL 通过调节肾内生性补体而促进肾小球微血栓的形成。

中文关键词： 抗磷脂抗体；肾脏；补体；血栓；肾炎

英文摘要： Antiphospholipid syndrome nephropathy (APSN) is related with the poor outcome of lupus nephritis. The pathogenesis of APSN is still unclear. Antiphospholilid antibody(aPL) is a group or profile of autoantibodies which can bind to coagulant factor. Previously, our prospective study find that lupus anticoagulant, anti-βglycoprotein I antibody, and anti-thrombin antibody are related with Glomerular microthrombosis (GMT) in lupus nephritis. Importantly, complements are involved the formation of GMT. In this study, we injected purified anti-βPI antiphospholipid antibody from APS patients into lupus mice. We fund that purified anti-βPI antibody can induce GMT formatiom in MRL/lpr mice, but normal human IgG do not has this funtion. Interestingly, anti-βPI antibody can not induce GMT in MRL/lpr and C57 mice. These studies indicated that aPL inducing GMT need background of inflammation. The effect of anti-βPantibody and normal IgG on kidney-derived complement indicated anti-βPI antibody can induce the expression of kidey-derived complement. And, anti-βPIantibody can not induce the expression of tissue factor. This study demonstrated that anti-βPI antibody can induce GMT and kidney-derived complement plays an rolr in the pathegenensis of APSN.

英文关键词： antiphospholipid antibody; kidney; complement;thrombosis; nephritis