CAJ | 학술논문

背景：目前阿尔茨海默病的病因、发病机制还不是十分清楚，很大程度上制约了阿尔茨海默病治疗药物的筛选，而主要障碍之一是缺少合适的动物模型。日趋成熟的转基因动物技术可以在活体上研究某一特定致病基因的作用，已成为阿尔茨海默病较为理想的动物模型。 　　目的：综述近几年国内外阿尔茨海默病转基因动物模型的研究进展。 　　方法：第一作者应用计算机检索2013年7月以前PubMed数据库、中国期刊全文数据库有关阿尔茨海默病转基因动物模型的文章，英文检索词为“Alzheimer’s disease, transgenic mouse, Animal model，dementia”，中文检索词为“阿尔茨海默病，转基因动物，动物模型，痴呆”。最终选择41篇文献进行综述。 　　结果与结论：阿尔茨海默病的病因是多元性的，遗传因素是其中的一个重要因素。现有的阿尔茨海默病转基因动物模型，包括单转基因模型、双转基因模型以及多重转基因模型。单转基因动物模型是通过重组DNA技术，将某一种突变的外源性基因片段整合到动物的基因组中，该模型只能研究阿尔茨海默病某一特定的病理变化；双转基因动物模型是通过重组DNA技术将两种外源性突变基因同时转染动物，相比单转基因模型，其病理变化与阿尔茨海默病更加吻合，但是仍然不能完全模拟疾病；多重转基因模型是利用不同的转基因鼠杂交或多个基因同时转入等方法，得到的多重转基因模型，该模型能更好的模拟临床阿尔茨海默病的发病过程和病理特征，但存在近亲衰退等缺点。各种动物模型都有其优点，但也存在着缺点，还需进一步建立更为完善的阿尔茨海默病转基因动物模型，更准确、完整地再现阿尔茨海默病的病理特征。
배경：목전아이자해묵병적병인、발병궤제환불시십분청초，흔대정도상제약료아이자해묵병치료약물적사선，이주요장애지일시결소합괄적동물모형。일추성숙적전기인동물기술가이재활체상연구모일특정치병기인적작용，이성위아이자해묵병교위이상적동물모형。 　　목적：종술근궤년국내외아이자해묵병전기인동물모형적연구진전。 　　방법：제일작자응용계산궤검색2013년7월이전PubMed수거고、중국기간전문수거고유관아이자해묵병전기인동물모형적문장，영문검색사위“Alzheimer’s disease, transgenic mouse, Animal model，dementia”，중문검색사위“아이자해묵병，전기인동물，동물모형，치태”。최종선택41편문헌진행종술。 　　결과여결론：아이자해묵병적병인시다원성적，유전인소시기중적일개중요인소。현유적아이자해묵병전기인동물모형，포괄단전기인모형、쌍전기인모형이급다중전기인모형。단전기인동물모형시통과중조DNA기술，장모일충돌변적외원성기인편단정합도동물적기인조중，해모형지능연구아이자해묵병모일특정적병리변화；쌍전기인동물모형시통과중조DNA기술장량충외원성돌변기인동시전염동물，상비단전기인모형，기병리변화여아이자해묵병경가문합，단시잉연불능완전모의질병；다중전기인모형시이용불동적전기인서잡교혹다개기인동시전입등방법，득도적다중전기인모형，해모형능경호적모의림상아이자해묵병적발병과정화병리특정，단존재근친쇠퇴등결점。각충동물모형도유기우점，단야존재착결점，환수진일보건립경위완선적아이자해묵병전기인동물모형，경준학、완정지재현아이자해묵병적병리특정。
BACKGROUND:Alzheimer’s disease causes and pathogenesis remain unclear, which greatly restrict the screening of drugs. And the main reason is lack of suitable animal models. The developing transgenic animal technology al ows studying the role of certain pathogenic gene in vivo, and has regarded the ideal animal models for Alzheimer’s disease. OBJECTIVE:To summarize the research advance of Alzheimer’s disease transgenic animal models. METHODS:Using“Alzheimer’s disease, transgenic mouse, animal model, dementia”in Chinese and English as the key words, the first author retrieved PubMed and CNKI databases published before July 2013. Final y, 41 articles were included in result analysis. RESULTS AND CONCLUSION:The etiology of Alzheimer’s disease is diverse, and genetic factor is one important factor. The existing transgenic animal models of Alzheimer’s disease include single genetical y modified models, double genetical y modified models and multiple transgenic models. Single transgenic animal models can make a kind of mutated exogenous gene integrate into the genomes of animals by using recombinant DNA technology. This kind of models can be applied to only study one specific pathological change of Alzheimer’s disease. Double transgenic animal models can make two kinds of mutated exogenous gene integrate into the genomes of animals and simultaneously transfect animals by using recombinant DNA technology. This kind of models is closer to the pathological changes of Alzheimer’s disease than single transgenic animal models, but stil cannot simulate Alzheimer’s disease. Multiple genetical y modified models are obtained with different transgenic mice hybridization or several genes transfection, which are most similar to clinical process and pathological features of Alzheimer’s disease. However, this kind of models may develop a decline in consanguinity. Each kind of animal model has their advantages and shortcomings, and a better transgenic animal model is urgently needed to completely simulate pathological characteristics of Alzheimer’s disease.