本文選題：去唾液酸蛋白受體　切入點(diǎn)：自身免疫性肝炎　出處：《鄭州大學(xué)》2015年碩士論文

【摘要】：背景:自身免疫性肝炎(autoimmune hepatitis,AIH)是與機(jī)體自身免疫相關(guān)的,病因和發(fā)病機(jī)制尚未研究清楚的肝臟疾病。研究認(rèn)為,自身免疫性肝炎肝損傷主要機(jī)制涉及兩個(gè)方面:T細(xì)胞介導(dǎo)的細(xì)胞毒性作用和抗體依賴(lài)性細(xì)胞介導(dǎo)的細(xì)胞毒性作用。但以哪種研究機(jī)制為主,尚未定論。而細(xì)胞因子的變化貫穿整個(gè)損傷機(jī)制。近年來(lái),大量研究發(fā)現(xiàn),肝細(xì)胞表面的去唾液酸蛋白受體(Asialoglycoprotein receptor,ASGPR)與自身免疫性肝炎發(fā)病有很大關(guān)聯(lián)。Hep G2細(xì)胞的去唾液酸蛋白受體在IL-1、IL-6等不同細(xì)胞因子的刺激下合成的數(shù)量和配體結(jié)合活性會(huì)發(fā)生變化。目前,關(guān)于自身免疫性肝炎相關(guān)白介素IL-2、IL-12、TNF-α對(duì)去唾液酸蛋白受體合成的影響報(bào)道較少。去唾液酸蛋白受體在自身免疫性肝炎相關(guān)白介素的影響下,對(duì)其合成的影響分析,無(wú)疑能提高去唾液酸蛋白受體對(duì)自身免疫性肝炎肝損傷機(jī)制的認(rèn)識(shí)。目的:研究自身免疫性肝炎相關(guān)白介素IL-2、TNF-α、IL-12對(duì)Hep G2細(xì)胞合成ASGPR的影響,從而為自身免疫性肝炎的肝損傷機(jī)制提供新線索。方法:1.采用RT-PCR方法檢測(cè)Hep G2細(xì)胞在TNF-a、IL-2和IL-12刺激2h、20h、24h后的ASGPR1m RNA和ASGPR2 m RNA表達(dá)量變化。2.Western Blot檢測(cè)Hep G2細(xì)胞在TNF-α、IL-2、IL-12刺激后2h、20h、24h后合成表面ASGPR蛋白變化。3.免疫組織化學(xué)法檢測(cè)AIH患者肝細(xì)胞表面ASGPR表達(dá)情況。結(jié)果:1.TNF-α可同步作用于ASGPR1m RNA和ASGPR2 m RNA,2h與20h表達(dá)量不同,差異有統(tǒng)計(jì)學(xué)意義(P1=0.002,P2=0.000);IL-2不能同步作用ASGPR1m RNA和ASGPR2 m RNA,ASGPR1m RNA呈先下降后上升趨勢(shì),20h與24h表達(dá)量差異有統(tǒng)計(jì)學(xué)意義(P=0.046),ASGPR2 m RNA呈先上升后下降趨勢(shì),2h與20h、2h與24h表達(dá)量差異均有統(tǒng)計(jì)學(xué)意義(P=0.001、P=0.000);IL-12不能同步作用ASGPR1m RNA和ASGPR2 m RNA,ASGPR1m RNA呈先下降趨勢(shì),2h與24h表達(dá)量差異有統(tǒng)計(jì)學(xué)意義(P=0.042),ASGPR2 m RNA呈先上升后下降趨勢(shì),表達(dá)量無(wú)差異(χ2=3.289,P=0.193)。2.Hep G2細(xì)胞表面ASGPR蛋白表達(dá)量:在TNF-α刺激下。24h內(nèi)呈現(xiàn)上升趨勢(shì)(P0.05);在IL-2刺激下,24h內(nèi)呈現(xiàn)下降趨勢(shì)(P0.05);在IL-12刺激下,呈先上升后下降趨勢(shì)(P0.05)。3.AIH患者肝細(xì)胞ASGPR表達(dá)減少,膽小管表面出現(xiàn)表達(dá)。結(jié)論:1.細(xì)胞因子TNF-α、IL-2、IL-12可直接影響ASGPR合成。肝細(xì)胞表面ASGPRS數(shù)量的變化可能參與到AIH肝損傷機(jī)制。2.TNF-α在24h內(nèi)基本可同步作用于ASGPR1m RNA和ASGPR2 m RNA,IL-12、IL-2則不能同步作用于ASGPR1m RNA和ASGPR2 m RNA。
[Abstract]:Background: autoimmune hepatitis autoimmune hepatitis (AIH) is a liver disease associated with autoimmune, etiology and pathogenesis.It is suggested that the mechanism of liver injury in autoimmune hepatitis involves two aspects: the cytotoxicity mediated by T cells and the cytotoxicity mediated by antibody dependent cells.However, which kind of research mechanism is the main, has not yet been concluded.The change of cytokines throughout the damage mechanism.In recent years, a large number of studies have found thatThe sialic acid protein receptor Asialoglycoprotein receptor (ASGPRR) on the surface of hepatocytes is closely related to the pathogenesis of autoimmune hepatitis. The amount and ligand binding activity of sialic acid protein receptor in Hep G2 cells stimulated by different cytokines such as IL 1 and IL 6 may change.At present, there are few reports about the effect of IL-12 TNF- 偽 on sialic acid receptor synthesis in autoimmune hepatitis.The effect of sialic acid protein receptor on the synthesis of sialic acid protein receptor under the influence of autoimmune hepatitis related interleukin can undoubtedly improve the understanding of the mechanism of liver injury caused by sialic acid protein receptor in autoimmune hepatitis.Aim: to study the effect of interleukin-2 (IL-2TNF- 偽) IL-12 on the synthesis of ASGPR in Hep G2 cells, and to provide a new clue for the mechanism of liver injury in autoimmune hepatitis.Method 1: 1.The expression of ASGPR on hepatocytes in patients with AIH was detected by immunohistochemical method.Results 1. TNF- 偽 could simultaneously act on ASGPR1m RNA and ASGPR2 m RNAs for 2 h and 20 h respectively.There was expression on the surface of the bile duct.Conclusion 1.Cytokine TNF- 偽 and IL-2 IL-12 can directly affect the synthesis of ASGPR.The changes of ASGPRS number on the surface of hepatocytes may be involved in the mechanism of AIH liver injury. 2. TNF- 偽 can act synchronously on ASGPR1m RNA and ASGPR2 m RNA-IL-12 / IL-2 within 24 hours, but not on ASGPR1m RNA and ASGPR2 m RNA.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R575.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前5條

1 王宵偉;抗去唾液酸糖蛋白受體與自身免疫性肝炎[J];國(guó)外醫(yī)學(xué)(消化系疾病分冊(cè));2000年01期

2 范列英,仲人前,屠小卿,Thomas Pfeiffer Ralph Feltens,朱燁,周琳;腫瘤壞死因子α基因多態(tài)性與中國(guó)人自身免疫肝病相關(guān)性研究[J];中華肝臟病雜志;2004年03期

3 Diego Vergani;Giorgina Mieli-Vergani;;Aetiopathogenesis of autoimmune hepatitis[J];World Journal of Gastroenterology;2008年21期

4 Dimitrios P Bogdanos;Diego Vergani;Pietro Invernizzi;Ian R Mackay;;Autoimmune liver serology:Current diagnostic and clinical challenges[J];World Journal of Gastroenterology;2008年21期

5 戴金津;郜玉峰;湯磊;李旭;鄒桂舟;;IL-12在慢性HBV攜帶者肝臟組織中的表達(dá)及其意義[J];中華實(shí)驗(yàn)和臨床感染病雜志(電子版);2013年03期

，

本文編號(hào)：1725692