【作者】 李秀源；

【导师】 单兆伟；

【作者基本信息】 南京中医药大学 ， 中医内科， 2009， 博士

【摘要】 目的与意义:胃癌是我国病死率最高的恶性肿瘤之一。临床上外科治疗的患者早期胃癌约有5%,进展期胃癌约有50%,在5年内因复发而死亡,即使作了根治性手术,仍有30%-80%发生局部或远处复发。因此,如何减少或阻止肿瘤复发转移,提高中晚期胃癌患者的临床疗效和远期生存率,是目前最迫切的研究课题。研究表明:胃癌的发生是一个多阶段、多因素的复杂发展过程。肿瘤的发生和发展不仅与肿瘤细胞的增殖和分化异常有关,而且与细胞凋亡基因和蛋白的变化有关,其调节机制紊乱将导致肿瘤的发生。因此,诱导细胞凋亡的策略成为近年来肿瘤治疗的重点。中医中药在肿瘤治疗领域的作用越来为人们所重视,为进一步阐明其作用机理,人们从细胞凋亡及其相关蛋白、基因表达的角度进行了大量研究。大量研究表明:中药中的许多成分可阻断肿瘤的发生和发展,具有良好的预防和治疗肿瘤的作用,对胃癌术后复发与转移的治疗有独特的优势。本研究是针对胃癌术后“正气亏虚,伏邪内蕴”的病机特点,以“益气养阴,解毒化瘀法”为治法而制定的芪竹方,进行了实验和临床两方面研究,验证其治疗胃癌术后的疗效,并系统的从理论和临床两方面阐述其作用机理,为胃癌术后的治疗探索可借鉴的方法和思路,为抗肿瘤术后复发、转移的基础研究提供临床基础。方法:1.临床部分:纳入符合胃癌术后诊断标准的35例患者,采用自身前后对照的方法进行治疗,采用QLQ-C30调查表,调查芪竹方治疗患者治疗前后生存质量变化的影响,同时总结导师防治胃癌术后复发与转移的学术思想。2.实验部分:常规培养人胃癌细胞MGC-803,通过MTT、流式细胞仪、电镜、蛋白印迹等方法,探讨芪竹方对人胃癌细胞MGC-803的增殖与凋亡机制的影响。结果:1.芪竹方具有提高胃癌术后患者生存质量的作用,疗前与疗后比较,差异显著（P＜0.05）。2.芪竹方抑制人胃癌细胞MGC-803的生长、使细胞周期阻止在G₁期,诱导细胞凋亡。3.芪竹方可改变线粒体跨膜电位ΔΨm,上调cytochrome c蛋白的表达。结论:1.芪竹方能够显著改善患者生存质量,是胃癌术后抗复发与转移的有效方剂。2.芪竹方能够诱导人胃癌细胞MGC-803发生凋亡,其机制与线粒体途径有关。更多还原

【Abstract】 Objective:Gastric cancer is one of the highest fatality and malignant tumor in China.Clinically, the patients with surgical treatment of about 5%early gastric cancer,about 50%advanced gastric cancer died in 5 years due to relapse,even made a radical operation,there is still 30% -80%of local or distant recurrence.Therefore,it is the most pressing issues to be addressed that how to reduce or prevent tumor recurrence and metastasis,to improve the clinical efficacy and long-term survival in patients with advanced gastric cancer.Studies show that the incidence of gastric cancer is a multi-stage and multi-factor in the complex process of development.Tumor occurrence and development is not only a process of tumor cell proliferation and differentiation abnormalities,but also a process of anti-apoptosis in the changes in gene and protein,and the adjustment mechanism of the disorder will lead to the occurrence of tumor.Therefore,the induction of apoptosis in cancer becomes an important strategy in recent years.The role of Chinese medicine in the field of cancer therapy is increasingly important for the people.In order to further elucidate its mechanism,it is of view a great deal of research from the cell apoptosis to its associated protein,gene expression point.Large number of studies showed that many of the components of traditional Chinese medicine may block the tumor occurrence and development of a sound prevention and treatment of tumors,and it has a unique advantage on the effect of postoperative recurrence and metastasis of gastric cancer treatment.We draft for the rule of Yiqi Yangyin,Jieduhuayu Law and the QiZhu formulae by the characteristics of postoperative gastric cancer research.Therefore,we carried out both experimental and clinical studies to validate its efficacy and mechanism from both theoretical and clinical aspects after the treatment of gastric cancer.We explore the treatment of gastric cancer patients to learn from the methods and ideas for the therapy of tumor recurrence and metastasis.Methods:1.Clinical parts:we investigate the influence on the quality of life by the Quality of life questionnaire-Core30 and to sum up mentor Prevention of postoperative recurrence and metastasis of gastric cancer of academic thought.2.Experimental parts:In order to observe the effects of proliferation and apoptosis on Human Stomach Cancer Cell Line MCG-803 induced by Qi Zhu Formulae,we cultured the cells with routine methods and used the method of Flow cytometry and Western blot.Results: 1.The quality of survivals could be improved by Qi Zhu Formulae,and there is significant difference(p＜0.05).2.The growth of Human Stomach Cancer Cell Line MCG-803 could be effectively prohibited by Qi Zhu Formulae,and cell cycle was arrested on G1 phase.3.The expression of cytochrome c and changes of mitochondrial membrane potential could be induced by Qi Zhu Formula.Conclusions:1.The quality of survivals could be improved by Qi Zhu Formula,and it is an effective medicine that could prevent the recurrence of gastric cancer.2.Mitochondrial pathway plays an important role in the apoptosis on human stomach cancer cell line MCG-803 induced by Qi Zhu Formulae.更多还原