本文選題：穿入 + 自身免疫性肝炎　； 參考：《上海交通大學(xué)》2014年博士論文

【摘要】：背景:病理組織學(xué)在自身免疫性肝病(AILD)的診斷中起重要作用。穿入現(xiàn)象雖然作為自身免疫性肝炎(AIH)的病理表現(xiàn)之一受到重視,但其細(xì)胞類型、結(jié)局及機(jī)制缺乏深入研究。而原發(fā)性膽汁性肝硬化(PBC)最新的病理組織學(xué)分級分期系統(tǒng)尚未在中國人群得以運(yùn)用。第一部分自身免疫性肝炎穿入現(xiàn)象臨床病理意義初探目的:研究穿入現(xiàn)象在AIH診斷中的價(jià)值,發(fā)生穿入的細(xì)胞類型、結(jié)局及其可能的機(jī)制方法:選取我院肝活檢病人294例(AIH101例,PBC 67例,DILI43例,CHB74例,NASH 9例),比較不同病種間穿入現(xiàn)象出現(xiàn)的概率,明確其在AIH診斷中的意義;分析AIH中穿入現(xiàn)象與臨床生化指標(biāo)及其他組織學(xué)表現(xiàn)的相關(guān)性;通過激光共聚焦技術(shù)明確穿入細(xì)胞的類型。采用免疫磁珠分選技術(shù)分離人CD8 T細(xì)胞與張氏肝細(xì)胞系共培養(yǎng),探究穿入后細(xì)胞結(jié)局及發(fā)生穿入的可能機(jī)制。結(jié)果:1.與PBC、DILI、CHB和NASH相比,AIH患者發(fā)生穿入的概率明顯升高。AIH患者中,發(fā)生穿入組其血清ALT、AST及肝臟組織學(xué)炎癥、纖維化程度明顯高于無穿入組。CD8 T細(xì)胞是發(fā)生穿入的主要細(xì)胞類型。2.體外共培養(yǎng)提示AIH患者CD8 T細(xì)胞主動穿入人張氏肝細(xì)胞,CD44、p-ERM及F-actin在CD8 T細(xì)胞極化帽或偽足處聚集,導(dǎo)致穿入的發(fā)生。穿入后CD8 T大部分發(fā)生凋亡(TUNEL和cleaved caspase 3陽性),而在AIH組織學(xué)切片上還伴有肝細(xì)胞凋亡。激素預(yù)處理CD8 T細(xì)胞其穿入張氏肝細(xì)胞的能力下降。結(jié)論:穿入現(xiàn)象是AIH相對特異的組織學(xué)表現(xiàn),其與生化及組織學(xué)炎癥程度相關(guān)。CD8 T細(xì)胞是發(fā)生穿入的主要細(xì)胞,其通過CD44/p-ERM/F-actin信號通路穿入肝細(xì)胞后引發(fā)自身凋亡,這可能是機(jī)體反饋性抑制作用。第二部分原發(fā)性膽汁性肝硬化組織學(xué)新系統(tǒng)在中國患者中的運(yùn)用目的:比較新舊PBC組織學(xué)分級分期系統(tǒng),嘗試從組織學(xué)角度區(qū)分PBC和重疊綜合征。方法:選取我院PBC患者102例(其中重疊綜合征14例),根據(jù)新舊系統(tǒng)分別行組織學(xué)分析,比較其與臨床生化和預(yù)后的關(guān)系。聯(lián)合多項(xiàng)組織學(xué)表現(xiàn)鑒別PBC和重疊綜合征并對其可能機(jī)制做初步探索。結(jié)果:1.與舊系統(tǒng)相比,新系統(tǒng)能分別反映肝細(xì)胞和膽管細(xì)胞損傷程度,其與臨床生化指標(biāo)有更好的相關(guān)性,對預(yù)后也有一定的預(yù)測性。2.聯(lián)合肝臟炎癥活動度和CK7陽性肝細(xì)胞可鑒別PBC和重疊綜合征。3.CK7陽性細(xì)胞出現(xiàn)可能與重疊綜合征中肝細(xì)胞明顯損傷及TGF-?表達(dá)增高相關(guān)。結(jié)論:新的PBC分級分期系統(tǒng)能更好的反映肝臟和膽管損傷,聯(lián)合肝炎活動度和CK7可從組織學(xué)上鑒別PBC和重疊綜合征,這可能與重疊綜合征中肝細(xì)胞明顯損傷及TGF-?高表達(dá)相關(guān)。
[Abstract]:Background: histopathology plays an important role in the diagnosis of autoimmune liver disease (AILD). Penetration is regarded as one of the pathological manifestations of autoimmune hepatitis (AIH), but its cell types, outcomes and mechanisms are lacking in depth. The latest histopathological classification and staging system for primary biliary cirrhosis (PBC) is still available. The first part of the Chinese population was not used. The first part of the clinical pathological significance of autoimmune hepatitis penetration. Objective: To study the value of the penetration phenomenon in AIH diagnosis, the type of penetrated cells, the outcome and possible mechanism methods: 294 cases of liver biopsy in our hospital (AIH101, PBC 67 cases, DILI43 cases, CHB74 cases, NASH 9 cases), In comparison with the probability of the appearance of different types of disease, the significance of its AIH diagnosis was made clear. The correlation between the penetration of AIH and the clinical biochemical indexes and other histological features was analyzed. The type of cell was clearly penetrated through the laser confocal technique. The immunomagnetic bead sorting technique was used to separate the human CD8 T cells from the liver cell line. Explore the possible mechanism of after penetration and penetration. Results: 1. compared with PBC, DILI, CHB, and NASH, the incidence of penetration in AIH patients was significantly higher than that in.AIH patients. The serum ALT, AST, and histologic inflammation of the liver were found in the group of penetrant groups, and the degree of fibrosis was significantly higher than that in the non invasive.CD8 T cells. In vitro co culture suggests that CD8 T cells in AIH patients actively penetrate human hepatocytes, and CD44, p-ERM and F-actin gather in the polarization cap or pseudo foot of CD8 T cells, leading to the occurrence of penetration. After the penetration, the majority of CD8 T is apoptotic (TUNEL and cleaved 3 positive). Conclusion: penetration is a relatively specific histologic manifestation of AIH, which is associated with the degree of inflammation in.CD8 T cells, which are the main cells that are penetrated by the biochemical and histologic inflammation, which may induce self apoptosis through the entry of the CD44/p-ERM/F-actin signaling pathway into the liver cells, which may be the feedback inhibition of the body. Use. Second parts of the new system of primary biliary cirrhosis in Chinese patients: compare the new and old PBC histology grading and staging system, try to distinguish PBC and overlapping syndrome from the histological point of view. Methods: 102 cases of PBC patients in our hospital (14 cases of overlapping syndrome) were selected and compared with the old and new system, the comparison of the histological analysis was made. Compared with the clinical biochemistry and prognosis. The joint multinomial identification of PBC and overlapping syndrome and its possible mechanism are explored. Results: 1. compared with the old system, the new system can reflect the damage degree of hepatocyte and bile duct cell respectively. It has a better correlation with the clinical biochemical indexes and has a certain predictability to the prognosis. .2. combined liver inflammation activity and CK7 positive hepatocytes can identify PBC and overlap syndrome.3.CK7 positive cells may be associated with obvious liver cell damage and TGF- expression in the overlapping syndrome. Conclusion: the new PBC grading and staging system can better reflect the injury of liver and bile duct, and the combination of hepatitis activity and CK7 can be histologically studied. Identification of PBC and overlap syndrome may be related to the obvious damage of liver cells and the high expression of TGF- in overlap syndrome.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R575

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