胃癌血瘀证基因表达及细胞信号信道蛋白表达的研究

【作者】 陈怡宏；

【导师】 陈群；

【作者基本信息】 广州中医药大学 ， 中医诊断学， 2002， 硕士

【摘要】 恶性肿瘤以肿块为主要特征，属于中医“症瘕”、“积聚”范畴。中医认为，本病虽病因多端，但其病机主要是气滞而导致血瘀内结。目前，肿瘤的研究在病理生理、病理解剖、免疫及分子生物学方面均有涉及。但单独对肿瘤的发展过程与血瘀的关系研究较少，尤其对肿瘤发展过程血瘀证与相关基因表达的研究尚未见报导。胃癌为临床常见肿瘤之一，我们拟以胃癌血瘀证患者为研究对象，探讨不同证候与相关基因表达的关系。依目前公认的观点，将胃癌的发生分为慢性浅表性胃炎、肠上皮化生，伴异型增生、胃癌，胃部病变采用1991年指定国际通行SYDNEY分类系统，探究血瘀证与胃癌发生、发展之间的关系，为胃癌血瘀证候发展不同阶段提供诊断依据。 文献研究 本文复习了瘀血学说的形成及其与肿瘤的关系，并综述了现代近十年关于肿瘤血瘀证候的认识，及癌基因的产生和发展作了阐述。古人对肿瘤和血瘀证之间作了大量的阐述，认为肿瘤的形成和临床表现与血瘀证候密切相关。近代多从血液流变学、血小板的凝聚性及相关酶学的角度探讨肿瘤与血瘀的关系，发现肿瘤呈现浓、粘、聚等高凝状态，并认为是血瘀证的一个本质反应。随着分子生物技术的广泛应用，基因的表达与肿瘤的相关性研究日益受到重视，并使人们对肿瘤的认识更进——步深入。 临床实验研究 从临床上看，尽管胃癌患者的临床证候有肝胃郁热、脾胃虚寒、瘀毒内阻、痰湿凝结，但其中一以瘀毒内阻为主要表现的血瘀证最为常见。其中在我院回顾性病案资料调查中发现，浸润性胃癌约1／3出现血瘀证。本实验藉由DNA拓扑异构酶Ⅱ，Ki-67，磷酸化酪氨酸等细胞标记指数研究胃癌血瘀证四种症型之间的关系。 1．胃癌血瘀证与DNA拓扑异构酶Ⅱ表达的关系：DNA拓扑异构酶Ⅱ的生物学作用以调节控制DNA的超螺旋状态打结或解结DNA的还连体状态，从而间接地影响细胞内核酸代谢过程及直接参与那些需打断并重新连接DNA分子链的细胞过程，，DNA的重组，修复，转录及复制过程。当拓扑异构酶 11表达越低则胃癌血瘀证恶化越严重。 2．胃癌血瘀证与m67表达的关系：Ki个7表达与胃不典型增生程度，胃癌不同分化程度及胃癌组织学分型密切相关，检测Ki乃7的表达水平有助于胃癌恶性程度的判断，对指导临床治疗有一定意义。 3．胃癌血瘀证与磷酸化酪氨酸表达的关系：磷酸化酪氨酸在维持内皮细胞的完整性及调节其屏障功能上扮演重要的角色。蛋白磷酸化在细胞功能的调节中起重要的作用，酪氨酸是磷酸化的位点之一。磷酸化酪胺酸标记指数越高，可能与内皮细胞结构改变，血管通透性变化相关，而使血小板发生释放和聚集反应，促凝作用增强；造成血瘀症状更为严重。更多还原

【Abstract】 The study of blood stasis syndrome has made great achievement in the field of the integration of Traditional Chinese and Western Medicine, ft concludes the application of pathophysiology, pathological anatomy, immunology and other modem scientific technique. Molecular biology has been used widely in the field of medicine, but the study of blood stasis concerned with the gene and genie expression is fewer.Malignant tumor is characterized of the lump in the clinic. In traditional Chinese medicine, the lump is closely related to the blood stasis. The pathological mechanism is blood stasis due to qi stagnation. Gastric carcinoma is one of the most common tumors in the clinic. To research the relationship between the different stages of tumor and the expression of related gene, we study the gastric carcinoma. According to current proverbial views, the generation of gastric carcinoma is classified with chronic gastritis (abbreviate: CG), intestinal metaplasia(abbreviate: IM), gastric dysplastic epithelia (abbreviate: GDE) and gastric carcinoma(abbreviate: GC). We adopted the SYDNEY category’ system of international routine of the gastropathy to study the relationship between the blood stasis syndrome of different stages of gastric carcinoma and the degree and number of expression of oncogene and oncocyte. The aim is to provide the diagnosis proofs of the blood stasis syndrome of gastric carcinoma in the molecular level.Recent research shows that it is many factors leading to the generation of gastric carcinoma. The blood stasis syndrome of gastric carcinoma is summary manifestation of many factors caused. What’s more, study of oncogene is the hot spot of the study of tumor, so we try to study the relationship between the blood stasis of different stages of gastric carcinoma and the expression of related genes.l.The relation of the blood stasis syndrome of gastric carcinoma and DNAtopoII expression:The biology action of DNAtopoII contrast control the supercoil tie knot of DNA or antiknot symbody behavior of DNA.Indirect influence to the process of intercell nucleic acid metabolism and direct preventive to interrupt the chain of DNAmoIecul,DNA recombination.plerosis transcription replication process ?2. .The relation of the blood stasis syndrome of gastric carcinoma and Ki-67 expression:The Ki-67 with stomach atypical hyperplasia degree,gastric carcinoma anisodifferentiation degree, gastric carcinoma histology typing intimate correlation.lt helps to judge the malignancy degree expression level of gastric carcinoma ?3. The relation of the blood stasis syndrome of gastric carcinoma and Phosphotyosine expression: Phosphotyosine plays important role to maintenance the endothelial cell barrier. Tyosine is a site of phosphory .The exponent of thosphotyosine is higher,its maybe relationship with the endothelial cell structure and the blood vessel permeability.lt made the thrombocyiopoiesis releas and collecting response.Therefore the blood-stasis symptom became severity.更多还原