滋阴清热法调控骨髓EMP对狼疮鼠抗核抗体和幼红细胞孤核免疫效应的作用及机理研究

Our research found that nourishing yin and clearing heat herbs can decrease the lupus mice abnormal increase in anti nuclear antibody and bone marrow erythroblast macrophage protein (EMP). Bone marrow EMP connecte crucially erythroblast and macrophage and determine erythroblast enucleation and maturation. the erythroblast solitary nucleus which have no other components of the cell were phagocytosis by macrophage which has the antigen presenting function, The erythroblast solitary nucleus have an theoretic conditions to be unknown nuclear antigen to anti nuclear antibody. The nuclear antigen of lupus erythematosus has not been located which have always been tied up the study on mechanism of anti nuclear antibodies. According to the nourishing yin and clearing heat traditional Chinese medicine effect on antinuclear antibody and EMP in our research we present hypothesis that solitary nuclear could be the solution in nuclear antigen puzzle, higher EMP involve unknown pathogenesis of lupus anti nuclear antibody. To study effect of Ziyin Qingre method on antinuclear antibody, according to the nourishing yin and clearing heat treatment on lupus from the kidney, kidney affect the bone marrow in TCM theory, we introduce bone marrow EMP into lupus erythematosus research field, with lipopolysaccharide induced murine lupus multiple lupus activity, using nourishing yin and clearing heat medicine intervention. To observe Ziyin Qingre method regulation on EMP pathway effect on nuclear antibody mechanism and the influence on immunological changes of erythroblast solitary nucleus , with in vivo gene silencing EMP gene to explore the effects of Ziyin Qingre method regulation mechanism. study the role of EMP in the pathogenesis of anti nuclear antibodies and the localization of nuclear antigen of erythroblast solitary nucleus. The subject goal is: To break through the dilemma of the mechanism of SLE anti nuclear antibody. and promote the study of TCM lupus erythematosus

我们研究发现：中医滋阴清热药可以降低狼疮鼠抗核抗体和骨髓幼红细胞巨噬细胞连接蛋白（EMP）的增高。骨髓EMP关键性连接幼红细胞和巨噬细胞，决定幼红细胞脱核成熟。脱核后无细胞其他成分的幼红细胞孤核被有抗原呈递功能的巨噬细胞吞噬，孤核满足作为核抗原诱发抗核抗体的理论条件。红斑狼疮核抗原未能定位，一直束缚抗核抗体机理研究。本课题根据前期滋阴清热药对抗核抗体和EMP的作用，提出幼红细胞孤核是核抗原，EMP增高涉抗核抗体产生机理的假说，依滋阴清热法从肾论治狼疮，肾生骨髓之理，将骨髓EMP引入红斑狼疮研究领域，以脂多糖诱发狼疮鼠多重狼疮活动，滋阴清热中药干预，研究滋阴清热法调控骨髓EMP对狼疮鼠抗核抗体和孤核免疫效应的作用，基因沉默EMP等基因，明确中药的作用机理，研究抗核抗体病机中的EMP作用和孤核的核抗原定位。课题目标是突破SLE抗核抗体产生机理不清的困局，推进中医滋阴清热法治疗SLE机理研究。

抗核抗体形成机理不明，困惑SLE中西医研究。在骨髓：巨噬细胞(Mφ)产生EMP连接Mφ和 幼红细胞形成造血岛；Mφ吞噬红细胞成熟脱落的核，具备抗原呈递条件；病理条件下Mφ吞噬 受损核而成狼疮细胞；重度活动时Mφ吞噬幼红细胞而成噬血细胞。我们前期发现在骨髓：滋阴清热中药可降低脂多糖诱发的狼疮鼠Mφ表达红细胞脱核关键蛋白EMP、噬血细胞及抗核抗体形成。据此我们推测红细胞脱核异常可能是SLE新病机并诱发抗核抗体。本项目为研究抗核抗体的形成机制，以骨髓造血岛为载体,采用尾静脉注射佐剂siRNA基因沉默EMP，研究红细胞脱核异常对抗核抗体影响，并用滋阴清热药干预狼疮鼠，阐明中药对红细胞脱核异常的作用，筛选其环状RNA标志物，探索中药治疗SLE新机制及标志物。结果显示狼疮模型鼠骨髓 EMP 阳性细胞比正常对照组密集，基因表达增高，血清抗ds-DNA抗体浓度和尿蛋白也更高; 滋阴清热药狼疮模型鼠组与生理盐水狼疮模型鼠组EMP的基因表达组间比较明显下降，差异有统计学意义(P＜0.05);血清抗ds-DNA 抗体浓度和尿蛋白也明显下降，差异有统计学意义(P＜0.05)，提示EMP可能是滋阴清热药治疗SLE新的作用靶点。

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