精脒与疟原虫抗氯喹关系的研究

The Relationship Between Spermidine and Chloroquine Resistance of Plasmodium

抑制伯氏疟原虫感染RBC中50％精脒量,抗氯喹株需要喂服400mg/kg氯喹,而敏感的为20mg/kg,相差至少20倍。两株感染鼠同样喂服氟喹20mg/kg和400mg/kg一次,3小时后,在全血和感染RBC中的氯喹量,低剂量组接近,400mg/kg组抗氯喹的更高,而积聚在疟原虫中的氯喹量则抗氯喹的低于敏感。抗氯喹感染RBC中的精脒,78‰集中在疟原虫,故认为精脒量的提高,可能与氯喹进入疟原虫产生竞争性抑制。MGBG抑制抗氯喹鼠中的疟原虫生长,精脒能逆转其作用。

The dosage of chloroquine (CQ)required to inhibit 50% spermidine (SPD) levels in mice RBC infected with CQ-resistant (CR) and sensitive (CS) strains of P. berfjhei were found to be 400mg/kg and 20mg/kg respectively.Three hours after feeding CQ 20mg/kg or 400mg/kg, the content of the drug in whole blood and infected RBC of CR was higher than that in CS group, but CQ content in CR parasites was 64.8% less than CS (20mg/kg) .It has been found that 78.2% SPD was distributed in CR parasites. Since both CQ and SPD are polyamine compounds in chemical structure. The fact led us to suggest that the increased SPD in CR parasites might compete with CQ in entering into plasmodium.While methylglyoxal bis (guanylhydrazone) (MGBG) inhibited the growth of CR plasmodium, SPD in equal mole of MGBG could reverse the inhibition. Hence, SPD may play an important role in growth of plasmodium and formation of CQ resistance.