伯氏疟原虫对青蒿素抗药性的研究

仿Peters剂量递增法用伯氏疟原虫ANKA株及N株对QHS进行了抗药性的研究。经14个月的培育至第58代,QHS im注射“4日抑制性实验”的ED₅₀在RQ/ANKA系及RQ/N系分别为其亲代系的53.4及54.6倍,但经蚊传未获成功。在第40代(I₅₀=25)时,其50%的治愈剂量为其亲代系的5.4倍。停药传代其抗性会逐渐消失。该虫系对青蒿酯钠及蒿甲醚有明显的交叉抗性,其ED₅₀分别为其亲代系的13.1及11.7倍,对伯喹的抗性为2.9倍,对氯喹未见明显交叉抗性。

DEVELOPMENT OF QINGHAOSU-RESISTANT LINE OF PLASMODIUM BERGHEI ANKA AND N STRAIN

Qinghaosu (QHS) is a new antimalarial drug. Animal experiments and clinical observations indicate that QHS is highly effective against erythrocytic parasite with low toxicity and marked effect on chloroquine-resistant falciparum malaria. In order to explore the possibility of inducing resistant line of malarial parasites, we conducted an experimental study on this problem in plasmodium berghei ANKA and N strain.Using the method of "4-day suppressive test" and stepwise increasing doses of the drug in consecutive passages in mice, 2 Qinghaosu-resistant lines (RQ/ANKA and RQ/N) were developed after 58 passages during 14 months. But it failed to infect mosquitoes. The indexes of resistance (I₅₀) of RQ/ANKA and RQ/N line were 53.4 and 54.6 respectively. The RQ line exhibited Clear cross-resistance to artesunate and artemether for which the I₅₀ were 13,and 11 respectively, and a slight resistance to primaquine (I₅₀=2.8). No cross-resistance to chloroquine was found. Serial drug-free passages showed that the resistance of RQ line was unstable and sensitivity reverted towards normal after 13 passages in about 3.months.