转基因技术在鼻咽上皮细胞癌变中医病机研究中的应用  

Study on the TCM pathogenesis of nasopharyngeal epithelia carcinogenesis with the use of transgenic techniques

作　　者：田道法[1] 何迎春[1] 

机构地区：[1]湖南中医药大学中西医结合学院,长沙410007

出　　处：《怀化医专学报》2006年第1期1-7,共7页

基　　金：国家自然科学基金项目（30271678,30572408）

摘　　要：目的 探讨利用转基因技术研究鼻咽上皮细胞癌变中医病机的可行性及相关实践问题。方法 从鼻咽上皮细胞癌变的“气虚染毒”病机假说出发，通过分析其可能的相关性现代生物学基础和代表性指向基因，选取目的基因，显微注射法制备转基因小鼠，反复筛选，建立鼻咽癌前痛变纯系转基因小鼠模型，并以“益气解毒”法进行干预试验。反证模型动物的可靠性。结果 鼻咽癌“气虚染毒”中医病机假说的“气虚”部分与遗传背景有关，“染毒”部分与EB病毒感染活性有关，其可能的相关代表性指向基因分别为体细胞抑癌基因p53和EB病毒瘤基因LMP1。于C57BL／6J♀×CBA♂小鼠转入p53mt和EB病毒LMP1，经反复筛选，获得纯系转p53mt-LMP1基因小鼠品系，鼻咽、鼻腔耻膜等组织的目的基因表迭活性很高，并出现明显的上皮细胞异型性改变，显示了癌变发展趋势。经“益气解毒”中药的干预治疗，上皮细胞的异型性改变发展趋势出现抑制或逆转。结论 鼻咽上皮细胞癌变的“气虚染毒”病机假说具有特定的生物学基础。“气虚”状态由遗传因素决定，“染毒”之变由EB病毒瘤基因LMP1引起。“益气解毒”中药干预能够在很大程度上逆转由该病机诱发的鼻咽上皮细胞癌变进程。Objective To investigate the TCM pathogenesis of nasopharyngeal epithelia carcinogenesis with the use of transgenic techniques. Methods Based on the hypothesis of Qi deficiency inducing toxin-contamination for clarifying nasopharyngeal epithelia carcinogenesis, target genes responsible for this kind of carcinogenesis were appointed via a careful analysis on the possible modem biological scientific basis underlying thishypothesis and representatively responsible genes associated with it. Microinjection procedures were taken to prepare transgenic mice.Afterwards, repeated screening program was used to establish a strain of purebred transgenic mouse model with precancerous lesion in their nasopharynx. Then, an intervening herbal therapy under the direction of Qi-boosting and toxin-resolving principles was carfled out to block or reverse the pathogenic progress among these animal models for determine the reliability of this kind of animal model prepared in this way. Results According to the theoretic analysis on hypothesis of Qi deficiency inducing toxin contamination for precancerous lesion in the nasopharynx, it might be clarified that the part of Qi deficiency should be associated with the genetic background of this lesion and the part of toxin-contamination should be related with the infecting activity of EB virus. The representatively responsible genes associated with the hypothesis could be appointed as human p53 gene of somatic cells and as v-oncogene LMP1 of EB virus. Therefore, these 2 genes were selected as the target genes for preparing transgenic mouse model with this condition. The primary generation of transgenic mice was prepared viatransferring these 2 genes into C57BL/6J xCBA mice by means of microinjection procedures. Then, a strain of purebred transgenic mouse with transferred p53 mt-LMP1 genes was established through a screening program repeatedly carried out among these animals. The expressing activity of p53 mt, LMP1 genes was very high in the tissues of nasopharyngealepithelia and nasal mucosa,

关 键 词：鼻咽癌 医病机 气虚染毒 益气解毒 转基因 动物模型 

分 类 号：R273[医药卫生—中西医结合]