本文選題：可溶性CD40　切入點(diǎn)：肝炎　出處：《蘇州大學(xué)》2006年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：CD40是屬于腫瘤壞死因子受體(TNFR)超家族的Ⅰ型跨膜糖蛋白，表達(dá)在B細(xì)胞、單核／巨噬細(xì)胞、樹(shù)突狀細(xì)胞(DCs)等多種類(lèi)型細(xì)胞上，它與其配體CD40L(CD154)結(jié)合后在免疫應(yīng)答、免疫調(diào)節(jié)以及炎癥反應(yīng)等生理、病理過(guò)程中發(fā)揮重要作用。可溶性CD40(sCD40)與膜型CD40(mCD40)在體內(nèi)呈現(xiàn)共存現(xiàn)象，具有與CD40L結(jié)合的生物學(xué)活性，參與免疫應(yīng)答的調(diào)節(jié)，，可能是mCD40-CD40L相互作用的天然拮抗劑。正常人血清低表達(dá)sCD40分子，業(yè)已發(fā)現(xiàn)腎臟病、肝臟病、阿爾茨海默病、血液病等多種疾病患者血清sCD40水平明顯升高，且顯示與臨床病理或疾病進(jìn)程相關(guān)。體外實(shí)驗(yàn)顯示活化B細(xì)胞能夠釋放sCD40，但是sCD40是否還有其他細(xì)胞來(lái)源以及sCD40的產(chǎn)生機(jī)制和臨床意義尚待進(jìn)一步研究。 本研究第一部分系統(tǒng)分析了各種肝臟疾病患者血清中sCD40的表達(dá)及其與臨床生化指標(biāo)和病程發(fā)展的相關(guān)性。實(shí)驗(yàn)結(jié)果顯示，sCD40在各種肝病患者(急性肝炎、重型肝炎、肝硬化和原發(fā)性肝癌)血清較健康人異常升高(P＜0.001)，而且其水平與患者年齡呈弱負(fù)性相關(guān)。急性肝炎患者血清sCD40濃度與丙氨酸氨基轉(zhuǎn)移酶(ALT)、天門(mén)冬酸氨基轉(zhuǎn)移酶(AST)水平顯著正相關(guān)(r=0.59，p＜0.001：r=0.34，p＜0.01)，隨著肝功能恢復(fù)正常、病情好轉(zhuǎn)，其血清sCD40水平逐漸下降：急性肝炎男性較女性患者血清sCD40顯著升高(P=0.026)，提示性激素可能影響sCD40的產(chǎn)生。重型肝炎死亡患者sCD40濃度顯著高于存活患者(P=0.022)，而且并發(fā)肝性腦病患者顯著升高(P=0.018)，由此提示重型肝炎患者發(fā)病初期血清sCD40濃度越高，隨病情進(jìn)展患者并發(fā)肝性腦病和死亡的危險(xiǎn)性越大，患者血清中持續(xù)存在高水平的sCD40，提示預(yù)后不良。 業(yè)已有研究顯示B細(xì)胞釋放的sCD40是由TNF-α轉(zhuǎn)換酶(TACE，ADAM17)或其他金屬蛋白酶(MP)水解mCD40所致。課題第二部分進(jìn)一步探討了肝癌患者
[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- 偽 converting enzyme TNF- 偽 converting enzyme TACEE ADAM17 or other metalloproteinases.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類(lèi)號(hào)】：R575;R392

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 王靜艷,穆桂玲,劉沛,谷秋紅;乙型重型肝炎基因變異與免疫異常的關(guān)系[J];中華傳染病雜志;2001年02期

2 莊羽美,黃建安,朱華亭,周璇,馬泓冰,王鳳鳴,Elisabeth Monchatre,Léna Edelman,張學(xué)光;可溶性CD40酶聯(lián)檢測(cè)試劑盒的研制及其檢測(cè)的臨床意義[J];中國(guó)免疫學(xué)雜志;2004年08期

本文編號(hào)：1595664