药学学报, 1981, 16(4): 260-266
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陈林;戴祖瑞;马志明. 疟疾防治药物的研究——Ⅱ.疟疾病因性预防药物筛选试验动物模型 1.约氏鼠疟原虫—斯氏按蚊系统[J]. 药学学报, 1981, 16(4): 260-266.
Chen Lin; Dai Zurui and Ma Zhiming . STUDIES ON ANTIMALARIALS DRUG——Ⅱ. The causal prophylactic activity of antimalarial in animal model. Part Ⅰ. Plasmodium yoelii-Anopheles stephensi system[J]. Acta Pharmaceutica Sinica, 1981, 16(4): 260-266.

疟疾防治药物的研究——Ⅱ.疟疾病因性预防药物筛选试验动物模型 1.约氏鼠疟原虫—斯氏按蚊系统
陈林;戴祖瑞;马志明
第二军医大学寄生虫学教研室,上海
摘要:
为寻找新的疟疾病因性预防药物,我们建立了约氏鼠疟原虫—斯氏按蚊系统动物模型。实验证明,在一定条件下,斯氏按蚊的感染率为33±4.05%;小鼠易感性强,对照组的感染率相当稳定,可达94±0.011%。根据多次实验结果,提出了每鼠以一只阳性蚊感染,即时给药,连给三夭,然后在第7天和14天分别血检有无疟原虫,如阴性,则输血转种健康小鼠和切脾,再进行血检考核有无药效的简便过筛方法。在这一动物模型上,常用的抗疟药,如乙胺嘧啶、伯喹显示有病因性预防作用,而氯喹则无此作用。我们已用这一模型筛选了500余种化合物,证明方法可靠。至于如何区分药物对疟原虫红前期和红细胞内期的残留作用,在一般情况下区分并不十分困难,但对某些长效化合物,如有长效作用的喹哌等,则需通过食蟹猴疟原虫复筛,才能判定。
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STUDIES ON ANTIMALARIALS DRUG——Ⅱ. The causal prophylactic activity of antimalarial in animal model. Part Ⅰ. Plasmodium yoelii-Anopheles stephensi system
Chen Lin; Dai Zurui and Ma Zhiming
Abstract:
For the purpose of screening new causal prophylactic antimalarials, Plasmodium yoelii-Anopheles stephensi system was established. It was demonstrated from the exper-imental results obtained in 9. years that the infection rate of the Anopheles and the mice was 33±4.05% and 94±0.0011%, respectively. Mice were fairly susceptible to par-asite infection as shown by the more or less constant and high infection rate in the control groups of different batches of experiments. Based on the results of a number of experiments, a routine procedure is suggested for primary screening of drugs as follows. Mice are intraperitoneally injected with the sporozoites of P. yoelii at a rate of one infective mosquito per mouse. Immediately after infection the drug to be tested is ad-ministered in 3 consecutive days. Blood examinations are made for parasites on the 7th and 14th days after drug administration. In case of negative finding, blood pooled from about one half of the negative mice is subinoculated into normal mice, and the other half is splenectomized. Blood examinations are made again 1 and 2 weeks later to det-ermine the activity of the drug. A number of current antimalarial drugs were tested in the model with the result that drugs like pyrimethamine and primaquine exhibited causal prophylactic activity, whereas others like chloroquine not. More than 500 comp-ounds were screened by means of this system, the results indicated that it is a depend-able method for primary screening. As regards differentiation of causal prophylactic action of drug from its residual effect on the blood forms of parasites, it is not very difficult to distinguish both prophylactic and therapeutic actions of drug from each other. However, for some compounds like long-acting piperaquine, atebrine and so on, it is necessary to make a further study in the simian malaria model recommended by Schmidt.
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