新疆哈萨克族人群RA合并ACD患者证候因子分析及hepc、s-HJV水平与疾病活动相关性研究

Chronic anemia(ACD) is a common type of anemia associated with rheumatoid arthritis(RA). Combined anemia is an important factor to aggravate systemic symptoms and joint dysfunction in RA patients. A deeper understanding of the pathogenesis of RA-ACD is important for effective treatment. In vivo iron metabolism disorder may be an important way to induce RA-ACD, and the iron modulin(Hepcidin) is an important hormone regulating iron metabolism in the body, which can be phosphorylated by binding with ferric transporter 1(FP1) on the membrane of cells, and is eventually digested by the corresponding protein system, thus reducing the use of iron. The ferritin-regulated protein(HJV) is an upstream molecule that can regulate iron metabolism. It plays an important role in the expression of Hepcidin, while secretory HJV(s-HJV) inhibits the expression of ferritin by inhibiting the signaling pathway of bone morphogenesis. In this study, the possible mechanism of RA associated with ACD was investigated by detecting HEPC, s-HJV, and the correlation between RA-ACD and RA-ACD was investigated. Factor analysis was used to study the characteristics of syndromes of the disease, to elucidate the objective and standard syndromes distribution, and to provide evidence for the identification and treatment of TCM.

慢性病贫血（ACD）是类风湿关节炎（RA）所伴发的一种常见贫血类型。合并贫血是加重RA患者全身症状及关节功能障碍、影响预后的重要因素。深入了解RA-ACD的发病机制对寻找有效的治疗方案具有重要意义。体内铁代谢障碍是引起RA-ACD的重要途径，而铁调素（Hepc）是机体内重要的调节铁代谢肽类激素，铁调素调节蛋白（HJV）是一种可以调节铁代谢的上游分子，对Hepc的表达起着极其重要的调节作用，而分泌型HJV(s-HJV)通过抑制骨形态发生蛋白信号通路的传导，抑制铁调素的表达。本研究通过检测hepc、s-HJV水平，探讨RA合并ACD发生的可能机制，并结合多种炎症因子、类风湿相关生化指标，结合类风湿疾病活动性评分（DAS28），探讨其与哈萨克族人群RA-ACD患者疾病活动性之间的相关性；并应用因子分析法研究该病的证候要素特征，阐明客观、规范的证型分布规律,为中医辨治提供依据。

本课题通过调查问卷，统计分析哈萨克族RA-ACD中医证候分布的规律；对哈萨克族RA患者血清Hepc、s-HJV及多种炎症因子、类风湿相关生化指标的水平进行检测。收集乌鲁木齐、阿勒泰地区和塔城地区的调查问卷共329份，血清样本共320份。得出中医证候可分5类，寒热错杂兼肾虚气血不足证、痰瘀痹阻兼气血亏虚证、风寒痹阻兼气血亏少证、湿热瘀阻兼脾气虚证、气血两虚兼湿阻证。相关性研究得出寒热错杂兼肾虚气血不足证与ESR、CRP、DAS28评分均呈正相关，湿热瘀阻兼脾气虚证与DAS28评分呈负相关，气血两虚兼湿阻证与DAS28评分呈负相关；RA-ACD组Hepc、Hb、Tf低于RA组和对照组（p＜0.05）；s-HJV、SF、ESR、CRP均高于RA组和对照组（p＜0.05）；SI高于RA组低于对照组（p＜0.05）；IL-6高于对照组（p＜0.05），但与RA组间差异无统计学意义（p＞0.05）。RA组Hepc、SI、Tf、SF低于对照组（p＜0.05）；s-HJV、IL-6、ESR、CRP高于对照组（p＜0.05）。相关性分析Hepc与IL-6呈正相关，与DAS28呈负相关；s-HJV与IL-6、SI、ESR、Tf呈正相关；DAS28与SI、ESR、CRP呈正相关，Hb与SI、SF、ESR、CRP、s-HJV和DAS28呈负相关，p值均小于0.05。综上所述：通过因子分析法得出哈萨克族RA合并ACD患者的中医证候规律可分为5类，证候与部分实验室指标存在一定相关性；Hepc和s-HJV参与了RA-ACD疾病发展的过程，s-HJV可能是以代偿性增高的方式逆转炎症因子对Hepc的促表达作用；RA的疾病活动与GDF15等炎症指标和贫血的关系密切，血清Hepc水平随着DAS28水平的增高而减少，提示Hepc与RA患者的疾病活动度有一定关联；BMP/SMAD通路调控了Hepc的生成，从而影响造血功能；类风湿关节炎合并贫血患者体内HIF-1α含量异常升高，与机体铁代谢异常、炎症反应程度直接相关；RDW对RA-ACD诊断和病情活动度判定具有一定的临床价值。乌鲁木齐、塔城、阿勒泰三地RA患者在ESR、CRP、RF、Hb等指标上存在差异性，需因地制宜对其进行诊治。