Research On The Effects And Related Immunological Mechanism Of Zincpolyanemine Coordinate With Artemisinin Drugs Treating Artemisinin-resistant Plasmodium Berghei Malaria In Mice

Objective: 1.The artemisinin-resistant strains of Plasmodium berghei with stable resistance were cultivated.The artemisinin-resistant mouse malaria model of Plasmodium berghei was established and its resistance index was investigated.2.On the basis of the previous experiments,the use of zincpolyanemine range was narrowed.It was explored the dose of zincpolyanemine used in combination with coartem to achieve a good antimalarial effect.3.The effects of zincpolyanemine on serum Ig G content and phagocytosis of peritoneal macrophages in mice were investigated to study the immunological mechanism of antimalarial effects of zincpolyanemine.Methods: In accordance with the method of progressively increasing dose,this experiment continued to cultivate the artemisinin-resistant strains of Plasmodium berghei to the 60 th generation,the resistance index of the 60 th generation of strain was examined.The rate of protozoal infection was examined by blood smear and the resistant strain ED50 was measured to calculate the resistance index of the 60 th generation.In the antimalarial efficacy test,a 28-day cure method was used to establish an artemisinin-resistant mouse malaria model of Plasmodium berghei.Blood samples were collected after the last dose of 24 h and once a week after the 7th day.The rates of protozoal infection,negative conversion,re-ignition and 28-day cure rates were calculated for each group of mice.The effects of different doses of zincpolyanemine,coartem,artemisinin,and different doses of zincpolyanemine coordinate with coartem on artemisinin-resistant mouse malaria of Plasmodium berghei were investigated.ELISA was used to detect the Ig G content in the mouse serum,and then the peritoneal macrophage phagocytosis function test was performed.The effects of different doses of zincpolyanemine on serum Ig G and peritoneal macrophage phagocytosis percentages in mice were investigated.Results: 1.From the 53 rd generation of artemisinin-resistant strains of Plasmodium berghei to the 62 nd generation,the resistance index of the 60 th generation was calculated to be 15.78.Compared with the previous experiment,the resistance growth slowed down.2.1.75-fold,2-fold and 2.25-fold zincpolyanemine alone had inhibitory effects on artemisinin-resistant mouse malaria caused by Plasmodium berghei.The 2.25-fold zincpolyanemine dose group had a 66.77% conversion rate of protozoan parasites,but both had reactivation,can not reach cure for 28 days.3.2.5-fold of coartem and 3600.00 mg/kg/d of artemisinin had a good inhibitory effect on artemisinin-resistant mouse malaria of Plasmodium berghei,but its re-ignition rate was extremely high and could not be cured for 28 days.The strain was suspected of being resistant to coartem.4.Compared with the use of zincpolyanemine and coartem alone,the com bined use of 2-fold,2.25-fold zincpolyanemine and 2.5-fold coartem for artemis inin-resistant mouse malaria of Plasmodium berghei is relatively effective,and some mice can achieve 28 days to heal.5.1.75-fold,2-fold and 2.25-fold zincpolyanemine has no effect on the serum Ig G content and thymus index of normal mice,but the mouse spleen index slightly increases.6.The serum Ig G content and spleen index of mice infected with artemisinin-resistant strain of Plasmodium berghei increased,and the thymus index was almost normal.1.75-fold,2-fold and 2.25-fold zincpolyanemine has little effect on the thymus index of infected mice,but has an effect on the serum Ig G content and spleen index of infected mice.The serum levels of Ig G were increased in the 2-fold and 2.25-fold zincpolyanemine groups,and the spleen index was significantly lower in the 2.25-fold zincpolyanemine group.7.1.75-fold,2-fold,and 2.25-fold zincpolyanemine increased the percent phagocytosis of peritoneal macrophages in mice.Among them,2.25-fold of zincpolyanemine dose group had the highest percentage of phagocytosis.Conclusions: The 60 th generation Plasmodium berghei mouse model of artemis inin-resistance was established,with a resistance index of 15.75.Two-fold,2.25-fold zincpolyanemine and 2.5-fold coartem were relatively effective against art emisinin-resistant mouse malaria,and some mice could be cured for 28 days.Zincpolyanemine may improve the immune function of mice infected with arte misinin-resistant strains.