自身免疫性肝病临床病理组织学研究

发布时间：2018-06-08 16:56

本文选题：穿入 + 自身免疫性肝炎　；参考：《上海交通大学》2014年博士论文

【摘要】：背景:病理组织学在自身免疫性肝病(AILD)的诊断中起重要作用。穿入现象虽然作为自身免疫性肝炎(AIH)的病理表现之一受到重视,但其细胞类型、结局及机制缺乏深入研究。而原发性胆汁性肝硬化(PBC)最新的病理组织学分级分期系统尚未在中国人群得以运用。第一部分自身免疫性肝炎穿入现象临床病理意义初探目的:研究穿入现象在AIH诊断中的价值,发生穿入的细胞类型、结局及其可能的机制方法:选取我院肝活检病人294例(AIH101例,PBC 67例,DILI43例,CHB74例,NASH 9例),比较不同病种间穿入现象出现的概率,明确其在AIH诊断中的意义;分析AIH中穿入现象与临床生化指标及其他组织学表现的相关性;通过激光共聚焦技术明确穿入细胞的类型。采用免疫磁珠分选技术分离人CD8 T细胞与张氏肝细胞系共培养,探究穿入后细胞结局及发生穿入的可能机制。结果:1.与PBC、DILI、CHB和NASH相比,AIH患者发生穿入的概率明显升高。AIH患者中,发生穿入组其血清ALT、AST及肝脏组织学炎症、纤维化程度明显高于无穿入组。CD8 T细胞是发生穿入的主要细胞类型。2.体外共培养提示AIH患者CD8 T细胞主动穿入人张氏肝细胞,CD44、p-ERM及F-actin在CD8 T细胞极化帽或伪足处聚集,导致穿入的发生。穿入后CD8 T大部分发生凋亡(TUNEL和cleaved caspase 3阳性),而在AIH组织学切片上还伴有肝细胞凋亡。激素预处理CD8 T细胞其穿入张氏肝细胞的能力下降。结论:穿入现象是AIH相对特异的组织学表现,其与生化及组织学炎症程度相关。CD8 T细胞是发生穿入的主要细胞,其通过CD44/p-ERM/F-actin信号通路穿入肝细胞后引发自身凋亡,这可能是机体反馈性抑制作用。第二部分原发性胆汁性肝硬化组织学新系统在中国患者中的运用目的:比较新旧PBC组织学分级分期系统,尝试从组织学角度区分PBC和重叠综合征。方法:选取我院PBC患者102例(其中重叠综合征14例),根据新旧系统分别行组织学分析,比较其与临床生化和预后的关系。联合多项组织学表现鉴别PBC和重叠综合征并对其可能机制做初步探索。结果:1.与旧系统相比,新系统能分别反映肝细胞和胆管细胞损伤程度,其与临床生化指标有更好的相关性,对预后也有一定的预测性。2.联合肝脏炎症活动度和CK7阳性肝细胞可鉴别PBC和重叠综合征。3.CK7阳性细胞出现可能与重叠综合征中肝细胞明显损伤及TGF-?表达增高相关。结论:新的PBC分级分期系统能更好的反映肝脏和胆管损伤,联合肝炎活动度和CK7可从组织学上鉴别PBC和重叠综合征,这可能与重叠综合征中肝细胞明显损伤及TGF-?高表达相关。
[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.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R575

【相似文献】