青蒿琥酯联合克林霉素延缓恶性疟抗药性的实验研究

A study on artesunate combined with clindamycin to delay resistance of Plasmodium falciparum to artesunate in the laboratory

目的了解克林霉素与青蒿琥酯联用对抗青蒿琥酯恶性疟原虫是否有增效和延缓抗性作用。方法将恶性疟原虫用Trager法进行体外连续培养,待其正常生长后分组进行药敏试验。对照组单用青蒿琥酯处理,实验组用青蒿琥酯/克林霉素处理,然后在相同的培养时间内对两组虫株用相应的药物间断增加浓度进行刺激培育,在培育前及用药后不同时间用Rieckmann体外微量法测定其半数抑制量(ID50)。结果用药前青蒿琥酯和克林霉素对恶性疟原虫的ID50分别为14.4和14 610.4 nmol/L,两药联用时的ID50分别为青蒿琥酯6.4 nmol/L,克林霉素101.8 nmol/L。用药后90 d,对照组青蒿琥酯和克林霉素的ID50分别为273.8和24 815.2 nmol/L,实验组分别是49.6和23 859.4 nmol/L;停药后30 d对照组青蒿琥酯和克林霉素的ID50分别为155.8和21 543.2 nmol/L;实验组分别是32.0和15 487.4 nmol/L。结论青蒿琥酯和克林霉素联用有增效作用,能减缓恶性疟原虫对青蒿琥酯抗药性的产生速度。

Objective To ascertain whether or not artesunate（Art） combined with clindamycin（Cli） has a synergistic effect and whether the two delay the resistance of Plasmodium falciparum to Art.Methods A P.falciparum strain was cultured in vitro by Trager＇s method.Drug susceptibility was tested after parasites had grown normally.The control group was treated with Art and the test group was treated with Art/Cli.During the same culturing time in vitro,P.falciparum of the two groups was challenged at intervals with corresponding drugs in increasing concentrations.The ID50 of the drugs was assayed by Rieckmann＇s in vitro micro-technique before and after the drug（s） were administered at different times.Results The ID50 of Art,Cli and Art/Cli was 14.4,14 610.4,and 6.4/101.8 nmol/L,respectively,before contact with the drug（s）.After drugs were administered for 90 d,the ID50 of Art,Cli,and Art/Cli was 273.8,24 815.2,and 49.6,23 859.4 nmol/L,respectively,for the test group.Once the drugs were stopped for 30 d,the ID50 of Art,Cli,and Art/Cli was 155.8,21 543.2,and 32.0,15 487.4 nmol/L,respectively,for the test group.Conclusion Art combined with Cli has a synergistic effect and may delay the resistance of P.falciparum to artesunate.