【作者】 郭淑杰；

【导师】 王建华；

【作者基本信息】 广州中医药大学 ， 中西医结合临床（内科）， 2000， 博士

【摘要】 胃癌在世界范围内占各类恶性肿瘤死因第二位，在我国属于高发肿瘤，其发病率和死亡率均居恶性肿瘤的前位，且未见z有下降趋势。1992年我国恶性肿瘤死亡抽查调查资料表明，胃癌的死亡率为25.16/10万人口，并以每年1.27％的速度增长，如按照这一趋势发展，2000年我国死于胃癌的人口数将达到35万人。因此寻求有效的治疗方法，延长生存期，提高生存质量，降低死亡率，已成为迫在眉睫的问题。目前临床沿用的治疗方法仍以手术、放疗和化疗为主，这三种方法复发率和转移率高、生存质量较低，疗效不很理想，为此，肿瘤研究人员尝试将中药以单方、验方、辨证论治等方法，或结合手术、放疗、化疗，或单独应用于临床，并通过基础研究证实中药的多种作用，寻找作用机制以期研制出用量小、疗效显著的中药新制剂。 根据组织结构、生物学行为及流行病学特征，Lauren将胃癌分为肠型和弥漫型。其中肠型胃癌被确定是一个从慢性萎缩性胃炎→肠上皮化生→异型增生Ⅰ、Ⅱ、Ⅲ级→胃癌的演变过程。山东临朐县进行的调查显示，当地慢性胃粘膜疾病的发病率相当高，这可能是胃癌高发的主要原因。同时，调查还发现在当地的部分家庭中有胃癌的家族集聚现象。这进一步说明胃癌的发生、发展是一个多因素，多阶段的逐步演变过程，并受到了遗传因素的影响，其发病过程可能包含着复杂的分子病理机制。 当前的研究表明，许多疾病均与细胞中基因的相关改变有关，分离克隆定位药物作用敏感基因是从根本上了解药物作用机理和开发新的防治手段的基础。人类细胞中只有15％左右的基因处于开放状态，能表达为有功能的蛋白质；其余的处于关闭状态，正常情况下无功能，这类基因在机体内外环境变化时可发挥作用。人类基因表达信息库中约含15000种不同mRNA序列，低丰度的mRNA（小于总mRNA含量的0.5％，又称稀有mRNA）占总mRNA的30％左右。“静息基因”和稀有mRNA的存在已成为克隆新基因和研究基因功能的限速步骤。通过药物诱导，提高稀有mRNA的丰度，或诱导静息基因的表达，对目的基因的研究起了导向作用，特别是在研究肿瘤、心脑血管疾病、糖尿病、老年性痴呆等重大危害性疾病的药物敏感基因方面，以及在多环境因素参与的多基因疾病研究中，选择性研究单一因素作用于机体的分子生物学机制方面具有明显优势，这一新的研究策略日益受到人们的重视。 随着复关的指日可待，中医药因其低毒性和有效性愈加受到世界的关注，深入、客观、系统的基础研究将会加快中医药走向世界的进程，并可为开发高效、服用方便的中药新药奠定坚实的基础。广州中医药大学脾胃研究所对连黛片及其主要成分盐酸 广州中医药大学博士学位论文小劈碱防治胃癌的作用已进行了近5年的闹和贿颧劝叨究，己有结果表明盐酸J徽碱明显扔揣uBGC823、MGC803纵胃翩嚼蝴颊0诱铆棚…。本淑初步展开了连黛片的临床观察，撇一了盐酸刁梯绷测人胃癌细帆socszs的作用，希望通过寻找中药单体成分盐酸4’st，raixtr胃癌细胞峨隧因，为硼中药复方连黛片的药理u奠定些许基础。结果如下： 1．本文观察了连黛片对术后胃癌大肠癌患者症状和体征的影响，认为连黛片可改善术后胃癌大肠癌患者的症状于oth正，）馅提谦实热征象的患者，有效率达叨肪Vb叼树10例胃癌患者的生存质量有所提高。这些结果为后面的研究打下＊，后面的研究经初步阶段性统计也证实了这个趋势，并对生存质量量表有所改进。 2．本文进行了连黛片治疗前后术后胃癌大肠癌患者血3靓叫宦标志的u，结果单纯血清 CEA的检觎榷 3例结肠癌患者中阳性牵馒茗ul （D，但从全部病例看，CEA阳性检出率只为28．57o／o，无法做为连黛片l悯未疗效明彬H副示：CAt99的阳性率较高，经连黛片治疗后没有显著差异；与CMIRH检测则可使阳性率提高到80．95％，且受样本数目的增多和连黛片对CEA p结果④6J，连黛片治疗后患者血清CEA和CA 199 M明显陶氏与治疗前十卧比差异显著。认为CEA和CA 19D联合检狈0可为连黛片的疗效评价指标之一，连黛片对其有影响。 3．本文监测了连黛片v后术后胃癌 患者血清IL－2、TNF－Q，结果连黛片治疗后 11．．显著增高，TNF Q iii1y）a虽也有增高，但与对照组LI：lqg异不显著，提示连黛片可8眼有通过增强术后胃癌大肠癌患者免疫功s歇而起傈＋瘤的作用。后面的研究在此基础上增加了细W副示NK细胞涸骄OT细u定，连黛片对二者均有升高趋势。 4．根据血电尿龟雕测心 气肝气肾功鹏狈，连黛片没有明显溺u哦0 5．本论文观察了连黛片主要有效成分小粱碱对人胃癌细胞系BGC823细胞株的作用，认为50 p hl作用24小时可以明显改变BGC823细胞形态，抑制细胞增殖，将细胞阻滞于GI期，是进行深入研究比较理想的药物作用体系。 6．以 50 11 iml盐酸小梁碱作用于 BGC823细胞株 24 ’J’时为给药细胞，未经药物处理细胞为正常细胞，提取总 RNA，以锚定引物 API、APZ、APS和随机引物ARPI、ARPZ、AJp3、Aop4更多还原

【Abstract】 colon and rectum after surgery.Mortality of gastric carcinoma was the second highest in all kinds of malignant tumor,and its morbidity and mortality were higher in our country too,which have no declined trend. It becomes most pressing question that we find an effective cure method which can prolong survival time , improve the quality of life, and decrease the mortality. Now, the main treat methods of gastric carcinoma are surgery, chemotherapy and radiotherapy, whose effects are not very well because recurrence rate and metastasis rate are high and the quality of life is low. So turner researchers try to treat it with traditional Chinese medicine by single formula, experimental formula and Bianzhenglunzhi separately or combined with surgery, chemotherapy and radiotherapy, and prove their effects, find their mechinism in order to produce new dosage form whose dose is little and effect is well.Based on histology, biological behavior and epidemiological character, Lauren divided gastric carcinoma into intestinal type and diffuse type .The former was definited to be a process from atrophicans gastriti ?intestinal metaplasia ?allotypic hyperplasia, grade I , II, III,gastric carcinoma. Investigation in Linqu county of Shangdong province showed morbidity in diseases of chronic mucous were rather higher in area where incidence of gastric carcinoma is high,which might be the main factor of high gastric carcinoma incidence, moreover, this investigation showed there was family clusterimg of gastric carcinoma in part of families in this area, which3indicated incidence and development of gastric carcinoma were a gradually changed process with many factors and phases which was effected by hereditary factors and might be include comprehesive molecular pathological machinism.Recent studies indicated that many diseases related to gene chages in cell, so separation, cloning and localization of medicine-sensitive genes is base of finding radical machinism and exploiting new preventing and treating method. Human chromosome DNA is made up with 3X10"base pairs, included 100,000 genes in which there are more than 10,000 genes were cloned and located. Only 15% genes of human cell are open which can express functional protein. The others are rest and no function, but can effect when the condition out or in body change. Human gene expressional information bank includes about 15,000 different mRNA sequences. Low mRNAdess than 0. 5% total mRNA, also called rare mRNA) is about 30%of total mRNA. Rest gene and rare gene decelerate cloning new gene and studing gene function.Traditional Chinese medicine is attented for its low toxicity and effeciency along with coming of entering WTO, so deep, impersonal and systemic basal study on traditional Chinese medicine can accelerate process of its being accepted and lay a foundation for exploiting new medicine. Piwei institute of Guangzhou TCM university have researched on effect of preventing and curing gastric carcinoma with Liandaipian and its main element桞erberine. Some results showed Berberine decreased prolif ication and induced apoptosis of human gastric carcinoma cell line BGC823 and MGC803.We started primary clinical observation on effect of Liandaipian on therapy gastric carcinoma and colon and rectum carcinoma after surgery and separated target genes of Berberine acting on BGC823 in order to establish base for exploiting pharmacological machinism of Liandaipian. Results showed:1. Liandaipian improved evidently patient’s symptoms and signs, especially those companied with heat, whose effective rate was90%. Otherwise, it improved Quality of Life in 10 patients with gastric carcinoma after surgery.2. We determined tumor markers in patient’s serum before and after curing with Liandaipian.The results showed that CEA positive rate was 28. 75%, so CEA couldn’t be used to investigate Liandaipian’s clinical effect ;CA19~9 positive rate was higher than that of CEA, but there wasn’t difference between before and after therapy with Liandaipian. Positive rate was更多还原