可溶性CD40在肝脏疾病中的表达及其临床意义

发布时间：2018-03-11 00:03

  本文选题：可溶性CD40　切入点：肝炎　出处：《苏州大学》2006年硕士论文　论文类型：学位论文

【摘要】：CD40是属于肿瘤坏死因子受体(TNFR)超家族的Ⅰ型跨膜糖蛋白，表达在B细胞、单核／巨噬细胞、树突状细胞(DCs)等多种类型细胞上，它与其配体CD40L(CD154)结合后在免疫应答、免疫调节以及炎症反应等生理、病理过程中发挥重要作用。可溶性CD40(sCD40)与膜型CD40(mCD40)在体内呈现共存现象，具有与CD40L结合的生物学活性，参与免疫应答的调节，，可能是mCD40-CD40L相互作用的天然拮抗剂。正常人血清低表达sCD40分子，业已发现肾脏病、肝脏病、阿尔茨海默病、血液病等多种疾病患者血清sCD40水平明显升高，且显示与临床病理或疾病进程相关。体外实验显示活化B细胞能够释放sCD40，但是sCD40是否还有其他细胞来源以及sCD40的产生机制和临床意义尚待进一步研究。 本研究第一部分系统分析了各种肝脏疾病患者血清中sCD40的表达及其与临床生化指标和病程发展的相关性。实验结果显示，sCD40在各种肝病患者(急性肝炎、重型肝炎、肝硬化和原发性肝癌)血清较健康人异常升高(P＜0.001)，而且其水平与患者年龄呈弱负性相关。急性肝炎患者血清sCD40浓度与丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)水平显著正相关(r=0.59，p＜0.001：r=0.34，p＜0.01)，随着肝功能恢复正常、病情好转，其血清sCD40水平逐渐下降：急性肝炎男性较女性患者血清sCD40显著升高(P=0.026)，提示性激素可能影响sCD40的产生。重型肝炎死亡患者sCD40浓度显著高于存活患者(P=0.022)，而且并发肝性脑病患者显著升高(P=0.018)，由此提示重型肝炎患者发病初期血清sCD40浓度越高，随病情进展患者并发肝性脑病和死亡的危险性越大，患者血清中持续存在高水平的sCD40，提示预后不良。 业已有研究显示B细胞释放的sCD40是由TNF-α转换酶(TACE，ADAM17)或其他金属蛋白酶(MP)水解mCD40所致。课题第二部分进一步探讨了肝癌患者
[Abstract]:CD40 is a type I transmembrane glycoprotein belonging to the tumor necrosis factor receptor (TNFR) superfamily. It is expressed in B cells, monocytes / macrophages, dendritic cells and other types of cells. Soluble CD40s CD40 (soluble CD40sCD40) and membrane CD40mCD40 (MCD40mCD40) coexist in vivo and play an important role in the physiological and pathological processes such as immunomodulation and inflammatory response. They have the biological activity of binding to CD40L and participate in the regulation of immune response. It may be a natural antagonist of mCD40-CD40L interaction. The low expression of sCD40 molecules in normal serum has been found in patients with kidney disease, liver disease, Alzheimer's disease, hematologic disease and other diseases. In vitro experiments showed that activated B cells could release sCD40, but whether there were other cell sources in sCD40 and the mechanism of sCD40 production and clinical significance need to be further studied. The first part of this study systematically analyzed the expression of sCD40 in serum of patients with various liver diseases and its correlation with clinical biochemical indexes and course of disease. The serum levels of sCD40 in patients with acute hepatitis were significantly higher than those in healthy controls (P < 0.001), and the levels of serum sCD40 were negatively correlated with the age of the patients. The serum levels of sCD40 in patients with acute hepatitis were associated with alanine aminotransferase (alt) and aspartate aminotransferase (AST) water. P < 0. 59p < 0. 001: r = 0. 34p < 0. 01, with liver function returning to normal. The condition improved, The serum sCD40 level of patients with acute hepatitis was significantly higher than that of women, suggesting that sex hormone might affect the production of sCD40. The concentration of sCD40 in patients with severe hepatitis was significantly higher than that in patients living with severe hepatitis, and it was complicated with liver disease. In patients with encephalopathy, the serum sCD40 level was significantly higher than that in patients with severe hepatitis. The higher the risk of hepatic encephalopathy and death, the higher the level of sCD40 in serum, indicating poor prognosis. It has been shown that sCD40 released by B cells is caused by the hydrolysis of mCD40 by TNF- 伪 converting enzyme TNF- 伪 converting enzyme TACEE ADAM17 or other metalloproteinases.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R575;R392

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相关期刊论文 前2条

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2 庄羽美,黄建安,朱华亭,周璇,马泓冰,王凤鸣,Elisabeth Monchatre,Léna Edelman,张学光;可溶性CD40酶联检测试剂盒的研制及其检测的临床意义[J];中国免疫学杂志;2004年08期

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