| Objective:1.This study was designed to establish artemisinin-resistant Plasmodium berghei rodent malaria model and examine its resistance index.2.The purpose of this study was to test the effects of co-artemether,zincpolyanemine and zincpolyanemine coordinate with other Artemisinin antimalarial drugs on treatment Artemisinin-resistant Plasmodium berghei treating and Chloroquine resistant rodent malaria.3.This study also was designed to examine the antimalarial characteristics of zincpolyanemine and the efficacy differences of zincpolyanemine coordinate with other Artemisinin antimalarial drugs on Chloroquine resistant rodent malaria.Methods:Frist,we cultivated the artemisinin-resistant Plasmodium berghei strains,then we gradually increase dose of artemisinin to establish artemisinin-resistant Plasmodium berghei rodent malaria model via four days of drugs inhibition.we measured the blood smear negative conversion rate and ED50 by tail vein,and then calculated the resistance index of the last resistant strains.We got the equivalent dose of co-artemether,artemether,artemisinin,lumefantrine,and zincpolyanemine for treatment the Plasmodium berghei normal rodent malaria model,and we analyzed the difference of dose effect of co-artemether and zincpolyanemine at 1 times,1.5 times,2 times,2.5 times and 3 times of their equivalent treating the artemisinin resistant model of Plasmodium berghei malaria,then we analyzed the differences in efficacy of co-artemether,artemether,lumefantrine and zincpolyanemine against Plasmodium berghei chloroquine resistant rodent malaria.We used the parasitemia densities through blood smear 24h after taking the drugs,cure rate of 28 days and conversion rate to show the treatment effects of these drugs.Results:1.The amount of artemisinin given to plasmodium berghei normal strain was increased gradually to 53 generation,study the resistance index of the 50 generation,the ED50 reaches 3957.632 mg/kg,and Resistance index comes to 15.68.2.Inhibitory effect can be observed while giving co-artemether 1 times the equivalent dose and also 1.5 times,2 times,2.5 times,3 times the equivalent dose of co-artemether to artemisinin resistant rodent malaria of Plasmodium berghei,however none of the group has 100%cure rate in 28days,The negative conversion ratio between the groups was statistically significant.The co-artemether is observed suspected resistance when treating artemisinin resistant rodent malaria of Plasmodium berghei?Parasitemia densities>0.005?.The curative rate of co-artemether in the treatment of chloroquine resistant Plasmodium berghei rodent malaria can up to 100%in 28 days,while the curative rate of artemether,lumefantrine alone in the treatment of chloroquine resistant Plasmodium berghei rodent malaria was less than 100%.The negative conversion ratio between the groups was statistically significant.The artemether and lumefantrine is observed suspected resistance when treating chloroquine resistant rodent malaria of Plasmodium berghei.3.Inhibitory effect can be observed while giving 1 times,1.5 times,2 times,2.5times and 3 times the equivalent dose of zincpolyanemine to artemisinin resistant rodent malaria of Plasmodium berghei,however none of the group has 100%cure rate in 28days,The negative conversion ratio between the groups was statistically significant.The curative rate of 3 times the equivalent dose of co-artemether is the highest to artemisinin resistant rodent malaria of Plasmodium berghei in 28 days.But the mortality rate of 2.5 times and 3 times the equivalent dose of zincpolyanemine can approach 100%to artemisinin resistant rodent malaria of Plasmodium berghei in28 days.Zincpolyanemine has also directly effect on the treatment of normal Plasmodium berghei rodent malaria and Chloroquine resistant rodent malaria.4.The curative rate improved when zincpolyanemine combined with co-artemether in the treatment of artemisinin resistant Plasmodium berghei rodent malaria?P<0.05?.5.The curative rate of co-artemether and combined with zincpolyanemine in the treatment of chloroquine resistant Plasmodium berghei rodent malaria can up to 100%in 28 days,while the curative rate of artemether,lumefantrine alone and combined with zincpolyanemine in the treatment of chloroquine resistant Plasmodium berghei rodent malaria was less than 100%.Curative effect showed no significant difference when the co-artemether combined with zincpolyanemine?P>0.05?,while the curative rate improved when artemether and lumefantrine,combined with zincpolyanemine?P<0.05?.Conclusion:The experimental results show that the Plasmodium berghei artemisinin resistant rodent malaria model is establishing,the resistance index comes to 15.68;the co-artemether is observed suspected resistance when treating artemisinin resistant rodent malaria of Plasmodium berghei,the cultivation rate can not up to 100%though the doses of co-artemether are increased;co-artemether has better curative effect compared with artemether and lumefantrine 24h after taking the drugs,and the curative effect can be improved when combined with zincpolyanemine.Zincpolyanemine has directly effect on the treatment of Artemisinin-resistant Plasmodium berghei rodent malaria and Chloroquine resistant rodent malaria.Increasing zincpolyanemine dosages can improve drug efficacy,but the toxicity also can enhance. |
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