【作者】 刘飞飞；

【导师】 吕申；

【作者基本信息】 大连医科大学 ， 病理学与病理生理学， 2006， 硕士

【摘要】 目的:胃癌是我国最常见的消化道恶性肿瘤,其发病机制复杂。目前认为Hp(Helicobacter pylori, Hp)感染是胃癌发生的重要原因之一,但其确切的致癌机制仍不清楚,有研究表明Hp是通过影响细胞内基因修复系统的功能而在胃癌的发生过程中起作用的。通常认为,肿瘤的发生是基因突变异常累积的结果,而基因突变异常累积常是由细胞内修复系统功能缺陷无法及时准确的修复损伤的DNA造成的。人类细胞内存在着完整的修复系统,其中包括碱基切除修复系统(Base excision repair, BER)和同源重组修复系统(homologous recombination, HR)。BER的基本功能是切除和替换由体内外各种突变剂导致的DNA碱基损伤,该系统中任一基因突变,都会导致细胞BER功能缺陷,产生遗传不稳定性,肿瘤易感。HR是真核细胞修复DNA双链断裂(DNA double strand breaks, DSBs)的一个重要途径, HR相关基因的缺陷可引起DSBs修复减少,肿瘤发生率显著增加。Hp感染是否会通过影响碱基切除修复基因蛋白及同源重组修复基因蛋白的表达水平,使之不能有效的修复损伤DNA,进而导致细胞癌变呢?本实验通过分析非肿瘤患者胃炎粘膜上皮(正常粘膜)、癌旁粘膜上皮(癌旁粘膜)及癌细胞(胃癌)中Hp感染与碱基切除修复基因及同源重组修复基因蛋白表达的关系,探讨Hp致癌的可能分子机制。方法:标本选取自2002—2003年大连市胃镜活检病例,胃癌病例59例,同病例癌旁粘膜同时取材,胃炎病例29例。快速尿素酶法检测胃粘膜组织中Hp感染情况,免疫组织化学方更多还原

【Abstract】 Objective: Gastric carcinoma (GCa) is the most common cancer in our country, however its pathogenesis is unknown. Helicobacter pylori (Hp) is thought as one important reason of gastric carcinogenesis, which is not clear. Some researchs indicated that Hp could induce GCa by destroying the function of gene repair systems in cells. The carcinogenesis resulted from the abnormal accumulation of gene mutations, which was the result of repair system functional defect in cells. There are complete repair system in normal cells, including base excision repair system (BER) and homologous recombination repair system (HR). The function of BER is to excise and replace the DNA base damages, and any abnormal expressions of BER genes may lead to the defect of BER functions and furthermore cellular malignant transformation. HR can repair the DNA double strand breaks (DSBs) which is the most severe damage of DNA. It is not known whether Hp induce the occurrence of GCa by inhibiting the functions of BER genes and HR genes? This study is designed to answer the question by analyzing the relationship of Hp infection to expressions of BER genes (APE1, XRCC1) and HR genes (XRCC2, XRCC3) in gastric epithelia from volunteers (normal epithelium), the epithelia surrounding carcinomas (surrounding epithelium) and carcinoma cells (carcinoma), and then to explain the possible carcinogenesis induced by Hp infection.Methods: Gastric biopsy specimens of 29 gastritis and 59 GCa were got by endoscopy from 2002 to 2003 in Dalian. Guick-ureolytase method更多还原