本文選題：慢性乙型肝炎　切入點：免疫耐受　出處：《天津醫(yī)科大學》2006年碩士論文

【摘要】： 目的 乙型肝炎病毒(HBV)是導致肝臟疾病的主要致病因子,許多的慢性乙型肝炎患者最終可發(fā)展成為肝硬化和原發(fā)性肝癌。迄今為止,乙型肝炎的發(fā)病機理和HBV引發(fā)免疫耐受的機制尚未完全闡明。本課題研究慢性乙型肝炎患者免疫耐受期和免疫清除期體內淋巴細胞基因表達譜的差異,探討差異表達基因與HBV感染引起的免疫耐受及免疫清除的關系。 方法 選擇慢性乙型肝炎(HBskg、HBekg、HBcAb陽性)病例,根據(jù)丙氨酸氨基轉移酶(ALT)高低劃分免疫耐受組、免疫清除組;以健康查體者為正常對照組。采集新鮮血液,EDTA抗凝,淋巴細胞分離液分離淋巴細胞,一步法提取總RNA,用逆轉錄法標記cDNA探針,熒光染料Cy3標記正常對照組,Cy5標記免疫耐受組和免疫清除組。采用高通量基因表達譜芯片(7,267個基因)進行芯片雜交,使用ScanArray Express共聚焦掃描儀掃描基因芯片,PerkinElmer LAS軟件進行數(shù)據(jù)分析。 結果 比較免疫耐受組與正常對照組發(fā)現(xiàn)差異表達基因419個,表達上調206個,下調213個;免疫清除組與免疫耐受組差異表達基因共213個,上調111個,下調102個;兩組共有但差異表達方向相反的基因47個,在免疫耐受期表達下調但免疫清除期上調6個,在免疫耐受上調免疫清除期下調41個。 結論 使用表達譜基因芯片檢測慢性乙型肝炎患者免疫耐受、免疫清除期淋巴細胞的基因表達,結合HBV感染的自然史,初步建立了HBV免疫耐受及免疫清除發(fā)生時淋巴細胞的差異表達基因譜。 通過比對免疫耐受和免疫清除發(fā)生后基因表達譜的改變,篩選出47個發(fā)生反向差異表達的基因。這些基因的反向差異表達可能在HBV的免疫耐受和免疫清除中的發(fā)揮了重要的作用。其一方面揭示了HBV逃避宿主免疫系統(tǒng)清除時對淋巴細胞產生的主動性調節(jié)機制,另一方面反映了免疫清除發(fā)生時機體淋巴細胞應答調機制。
[Abstract]:Purpose. Hepatitis B virus (HBV) is a major cause of liver disease, and many patients with chronic hepatitis B can eventually develop cirrhosis and primary liver cancer. The pathogenesis of hepatitis B and the mechanism of immune tolerance induced by HBV have not been fully elucidated. To investigate the relationship between differentially expressed genes and immune tolerance and clearance induced by HBV infection. Method. According to the level of alanine aminotransferase (alt), the immune tolerance group was divided into immune tolerance group and immune clearance group, and the healthy examiner was used as the normal control group, and the fresh blood EDTA anticoagulant was collected. Lymphocytes were isolated from lymphocytes, total RNAs were extracted by one step method, and cDNA probe was labeled with reverse transcription method. Fluorescent dye Cy3 was used to label Cy5 in normal control group and immune tolerance group and clearance group. High throughput gene expression microarray (7267 genes) was used for microarray hybridization. ScanArray Express confocal scanner was used to scan gene chip Perkin Elmer LAS for data analysis. Results. There were 419 differentially expressed genes (206 up-regulated and 213 down-regulated) in the immune tolerance group and the normal control group, 213 differentially expressed genes were up-regulated and 102 down-regulated in the immune clearance group and the immune tolerance group. There were 47 genes in the two groups, which were down-regulated in immune tolerance phase but up-regulated in immune clearance stage, and 41 genes were down-regulated in immune tolerance up-regulated immune clearance phase. Conclusion. Expression profile gene microarray was used to detect immune tolerance and lymphocyte gene expression in patients with chronic hepatitis B, and combined with the natural history of HBV infection. The differentially expressed gene profiles of lymphocytes during HBV tolerance and immune clearance were preliminarily established. By comparing the changes of gene expression profiles after immune tolerance and immune clearance, 47 reverse differentially expressed genes were screened. The reverse differential expression of these genes may play an important role in the immune tolerance and clearance of HBV. On the one hand, it reveals that HBV evades the host immune system. The mechanism of active regulation of lymphocyte production, On the other hand, it reflects the mechanism of lymphocyte response regulation during immune clearance.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2006
【分類號】：R512.62;R392.1

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本文編號：1685485