Study On The Antimalarial Functions And Mechanisms Of Two Antimicrobial Peptides

Malaria is transmitted by Anopheles mosquito vectors and is one of the most deadly infectious diseases.According to the latest World Malaria Report,97 countries and regions are in the severe malaria endemic regions,mostly in the tropical regions of Africa.In 2013,198 million cases of malaria occurred globally and the disease led to 584,000 deaths.The burden is heaviest in the WHO African Region,where an estimated 90%of all malaria deaths occur,and in children aged less than 5 years,who account for 78%of all deaths.The rapid spread of multi-drug resistant parasite and the emergence of insecticide-resistant Anopheles mosquito increase the difficulty of malaria control.To control malaria,there is an urgent need to accelerate the pace of new antimalarials development.Antimicrobial peptides are widely distributed in plants and animals and are an important part of the innate immune system.Antimicrobial peptides have activities against bacteria,virus and protozoan along with other biological functions.Designing and modifying polypeptide based on known antimicrobial peptide has become a research direction of new anti-infection,antiprotozoal and antiviral drugs.There are two antimicrobial peptides for the study:LZ1,a new type of antimicrobial peptides,designed and synthesized on the basis of our previous work;antimicrobial peptide hepcidin derived from human liver.First,LZ1 and hepcidin were synthesized and their stuctures and antimicrobial functions were confirmed.Second,we established a stable murine model for erythrocytic Plasmodium berghei by quantitative infection via the tail vein.Third,we tested the antimalarial activity of LZ1 and hepcidin through 4-day suppression test and Rane's test.At last,we explored the antimalarial mechanism of these two antimicrobial peptides by cytokine detection.In our study,we found that LZ1 had significant antimalarial activity in the erythrocytic murine model.Antimicrobial peptides LZ1 and hepcidin could dose-dependently inhibite the growth of malaria in mice and prolong survival of infected mice.Antimalarial mechanism research of these two antimicrobial peptides exhibited that they could enhance the immune response of the host by regulating the secretion of two types of inflammatory factors(IL-6 and IL-10),accounting for the in vivo antimalarial activity.The study provided some support for development of new antimalarial medicines.