伯氏疟原虫氯喹抗性逆转的实验观察  

Search for reverser of chloroquine-resistance in Plasmodium berghei

作　　者：吴嘉彤[1] 兰勤娴[1] 王琴美[1] 潘星清[2] 

机构地区：[1]中国疾病预防控制中心寄生虫病预防控制所,世界卫生组织疟疾、血吸虫病和丝虫病合作中心,上海200025 [2]俄亥俄州立大学药学院,哥伦布 Ohio 43210

出　　处：《国际医学寄生虫病杂志》2010年第5期263-266,共4页International JOurnal of Medical Parasitic Diseases

摘　　要：目的寻找伯氏疟原虫氯喹抗性逆转剂。方法将健康昆明小鼠72只（雌、雄各半）每只腹腔注射0．2ml伯氏疟原虫ANKA株氯喹敏感系（chloroquine sensitive，CS）或由其选育的高抗氯喹系（chloroquine resistance，CR），按下述随机分组后灌胃给药治疗，观察各组疗效。（1）小鼠感染CS疟原虫30min后随机均分为4组，每组6只，给D-6182{（Z，Z）-N，N，N-三甲基-2，3-双[（1-氧代-9-十八碳烯酸）-氧代]-1-丙胺基盐酸盐}、C-2832[胆崮醇-3-N-（二甲胺基乙基）氨甲酸酯]、Ket（酮替酚）、0．1％西黄蓍胶（对照组），连续灌药5d。于D1至D7每天每鼠取尾血涂片作常规镜检，确定各实验组的原虫血症。（2）小鼠感染CR疟原虫后第3天随机均分为8组，每组6只，给D-6182、C-2832、Ket组、氯喹组、0．1％西黄蓍胶对照组及给予D-6182、C-2832、Ket后2h再加灌服小剂量12mg／（kg·d）氯喹（5％ED90），连续5d。每鼠于D4至D7每天取尾血涂片作常规镜检，确定各实验组的原虫血症，并计算各组的原虫减虫率。结果（1）感染伯氏疟原虫CS株的小鼠，分别灌服80ms／（kg·d）D-6182、120ms／（kg·d）C-2832或10ms／（kg·d）Ket连续5d，各给药组与对照组小鼠的原虫感染率自D1至D4逐日上升，至D4达峰值，D5时对照组小鼠原虫感染率继续上升，而各给药组维持在D4的峰值水平。（2）感染伯氏疟原虫CR株的小鼠给适宜剂量的C-2832、D-6182或Ket后2h加灌服小剂量氯喹12mg／（kg·d）（5％ED90），此后连续5d（D3-D7），于D4原虫减虫率可达到97．77％、99．28％或96．73％，而在D7可达到99．81％、98．87％或100．00％。结论C-2832和D-6182两种化合物对伯氏疟原虫CR株感染小鼠的氯喹抗性具有逆转作用，其逆转能力与Ket相当。Objective To search for reverser of chloroquine-resistance in Plasmodium berghei （P. berghei） ANKA. Methods Seventy-two healthy Kunming mice were each infected with ehloroquine sensitive （CS） or chloroquine resistance （CR） P. berghei ANKA respectively, then treated with various schedule of reversal agents C-2832 ,D-6182 or ketotifen（Ket） respectively with or without co-administration of low dose （5% ED90 ） of ehloroquine （ CQ ）. Schedule 1 ： mice infected with CS were randomly distributed into 4 groups, 6 mice in each group, 30 min after infection,then treated i.g. with D-6182, C-2832, Ket or 0.1% gum tragaeanth（control） respectively for 5 consecutive days. The parasitemia of each experiment group was then deter- mined by routine microscopic examination on blood smears from the tail blood of each mouse from D1 to D7. Schedule 2 ： mice infected with CR were randomly distriduted into 8 groups, 6 mice in each group, 3 d after infection, then treated i.g. with D-6182, C-2832, Ket,ehloroquine or 0. 1% gum tragaeanth （control） with or without co-administration of 12 mg/（ kg · d） chloroquine （5% ED90 ） 2 h after the first administration for 5 consecutive days. The parasitemia of each experiment group was then determined microscopically by examination on blood smears from the tail blood of each mouse from D4 to 07. The reduction rates of each group were calculated and compared between the groups with or without treatment of reverser. Results 1. The parasitemia of mice infected with CS was going up daily from D1 to D4 and reached the peak on D4 in all groups administered with 80 mg/（kg ·d） D-6182, 120 mg/（kg ·d） C-2832 or 10 mg/（kg · d） Ket for5 d. From D5 the parasitemia kept going up in control group while it kept at the level of D4 in all treated groups. 2. Chloroquine 12 mg/ （kg · d） administered i.g. 2 h after administration of C-2832 or D-6182 or Ket for 5 d（ D3-D7 ） could reach 97.77% , 99.28% or 96.73% of reduction rate of parasitemia on D4 an

关 键 词：伯氏疟原虫 氯喹抗性 逆转剂 

分 类 号：R382.31[医药卫生—医学寄生虫学]