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

【摘要】：背景:自身免疫性肝炎(autoimmune hepatitis,AIH)是與機體自身免疫相關的,病因和發(fā)病機制尚未研究清楚的肝臟疾病。研究認為,自身免疫性肝炎肝損傷主要機制涉及兩個方面:T細胞介導的細胞毒性作用和抗體依賴性細胞介導的細胞毒性作用。但以哪種研究機制為主,尚未定論。而細胞因子的變化貫穿整個損傷機制。近年來,大量研究發(fā)現(xiàn),肝細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)病有很大關聯(lián)。Hep G2細胞的去唾液酸蛋白受體在IL-1、IL-6等不同細胞因子的刺激下合成的數(shù)量和配體結(jié)合活性會發(fā)生變化。目前,關于自身免疫性肝炎相關白介素IL-2、IL-12、TNF-α對去唾液酸蛋白受體合成的影響報道較少。去唾液酸蛋白受體在自身免疫性肝炎相關白介素的影響下,對其合成的影響分析,無疑能提高去唾液酸蛋白受體對自身免疫性肝炎肝損傷機制的認識。目的:研究自身免疫性肝炎相關白介素IL-2、TNF-α、IL-12對Hep G2細胞合成ASGPR的影響,從而為自身免疫性肝炎的肝損傷機制提供新線索。方法:1.采用RT-PCR方法檢測Hep G2細胞在TNF-a、IL-2和IL-12刺激2h、20h、24h后的ASGPR1m RNA和ASGPR2 m RNA表達量變化。2.Western Blot檢測Hep G2細胞在TNF-α、IL-2、IL-12刺激后2h、20h、24h后合成表面ASGPR蛋白變化。3.免疫組織化學法檢測AIH患者肝細胞表面ASGPR表達情況。結(jié)果:1.TNF-α可同步作用于ASGPR1m RNA和ASGPR2 m RNA,2h與20h表達量不同,差異有統(tǒng)計學意義(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,20h與24h表達量差異有統(tǒng)計學意義(P=0.046),ASGPR2 m RNA呈先上升后下降趨勢,2h與20h、2h與24h表達量差異均有統(tǒng)計學意義(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,2h與24h表達量差異有統(tǒng)計學意義(P=0.042),ASGPR2 m RNA呈先上升后下降趨勢,表達量無差異(χ2=3.289,P=0.193)。2.Hep G2細胞表面ASGPR蛋白表達量:在TNF-α刺激下。24h內(nèi)呈現(xiàn)上升趨勢(P0.05);在IL-2刺激下,24h內(nèi)呈現(xiàn)下降趨勢(P0.05);在IL-12刺激下,呈先上升后下降趨勢(P0.05)。3.AIH患者肝細胞ASGPR表達減少,膽小管表面出現(xiàn)表達。結(jié)論:1.細胞因子TNF-α、IL-2、IL-12可直接影響ASGPR合成。肝細胞表面ASGPRS數(shù)量的變化可能參與到AIH肝損傷機制。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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R575.1

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本文編號：1725692