中文摘要
疟疾是一种严重危害人体健康的疾病。近年来,全球气候变暖,蚊媒分布区域扩大,疟疾仍无递减趋势, 成为世界上在疾病、死亡和经济损失方面最严重的虫媒传染病。本研究以中医理论为指导,采用复合因素,模拟自然感染方式,综合环境气候、体质及病原微生物等因素建立合适的鼠疟湿热证动物模型;培育出湿热证青蒿素和哌喹抗性株组和常态组,采用巢式PCR扩增全长基因,测序后以Mega软件分析比对,分析各抗药性相关位点的突变频率;并利用连锁不平衡分析、转基因方法寻找确定耐药基因;比较两种不同环境对青蒿素、哌喹耐药性的影响。评价复方青蒿素抗性与湿热环境的相关性,探索青蒿素抗性产生的机制,为进一步延缓复方青蒿素在亚非洲湿热环境疟区使用寿命提供依据;掌握区域环境恶性疟原虫对药物抗性的影响,分析恶性疟原虫在药物压力下是否存在疟原虫抗药性及基因多态性,让受疟疾危害的人民享受到中国中医药带来的福音。
英文摘要
Malaria is a serious disease that endanger human health. In recent years, mosquito-borne distribution area extends as the global becomes warming, and the trend of control malaria still pessimism. In the aspect of disease, death and economic loss, malaria becomes the most serious of insect-borne infectious diseases in the world. Guided by the theory of traditional of Chinese medicine, this study adopts complex factors, simulates of natural infection way, synthesizes environmental factors, habitus, constitution, and pathogenic microorganism to establish the malaria model with pattern of damp-heat, cultivates cell lines of Artemisinin group (including the resistance strain of Artemisinin and the normal) and Piperaquine group (including the resistance strain of Piperaquine and the normal) with pattern of damp-heat. With the nested PCR will be used to amplify of gene fragment and sequencing will be analyzed by Mega software for analysis of the mutation frequency of each drug resistance related sites. Thereafter, we may use the linkage disequilibrium analysis and genetically modified method to determine the resistance genes, then, compare between Artemisinin and Piperaquine in two different environment on the effect of resistance will be made.This study is to evaluatethe correlation of resistance of compound artemisinin and damp-heat environment, explorethe mechanism of resistance of artemisinin production, provide the evidence to prolong the usage of the compound artemisinin in Asia and Africa malaria area with damp-heat environment, grasp the rule of the regional environment of p. falciparum resistance to drugs, and analyze the resistance and gene polymorphism of p. falciparum under the presence of the malaria parasite drug. Victims of malaria people will enjoy the traditional Chinese medicine to bring the Gospel in China.
