伯氏疟原虫K173株对喹哌抗药性的实验研究

用小剂量递增法培育伯氏疟原虫对喹哌的抗药性,起始剂量7 mg/kg×1,每传三代递增3.5 mg/kg,至20代,历时5个多月,培育出对喹哌有110倍以上抗性的虫系。抗喹哌伯氏疟原虫系对羟基喹哌、甲氟喹、青蒿酯、青蒿素都有明显的交叉抗性,对咯萘啶、氯喹和伯喹仅有微弱交叉抗性;对乙胺嘧啶和硝喹显示高敏效应。但该虫系的抗性尚不稳定,停药后连续血传12代,抗性水平由110多倍降至8倍.

DEVELOPMENT OF PIPERAQUINE-RESISTANT LINE OF PLASMODIUM BERGHEI K173 STRAIN

Using an increasing dose pressure, a piperaquine-resistant line (PR line) in P. berghei K173 strain was developed. The starting dose was 7 mg/kg, about the total piperaquine ED₅₀ dose in the normal strain (parent line). The dose was increased by 3.5 mg/kg every three passages. Resistance detection test showed that the resistance level of PR line in passage 7 was 3.9 times that of the parent line, up to 75 times in passage 13, and>110 times in passage 20 in 5 months.The piperaquine-resistant line exhibited clear cross resistance to hydroxypiperaquine, mefloquine, qinghaozhi (artesunate), and qinghaosu (artemisinine). The resistance index (ED₅₀ in PR line/ED₅₀ in parent line) were 95.15, 45.27, 3.82, and 3.30 respectively. Its cross resistance, however, was slight to pyronaridine, chloroquine and primaquine, the resistance index being 1.55, 1.29, and 1.26, respectively. Towards pyrimethamine and nitroquine, the PR line displayed some hypersensitivity, the index being 0.82 and 0.55.With the augmentation of resistance, the course of infection of the PR line in mice was longer than that of parent line, indicating that the virulence dropped while resistance was raised. Serial drug-free passages showed that the resistance of PR line was unstable. Although the resistance level was not changed from passage 1 to 4, it dropped markedly from passage 5 onwards, and decreased from>110 to 8-fald after nassages 12.