The Study Of Relation Between Calcium/Angiogeesis Signal Pathway And Growth Status Of Hydatid

Objective: To discover some new targets of drug against echinococcosis or screen out new candidate drugs against echinococcosis on researching pharmacodynamics of verapamil,masoprocol and apatinib against echinococcosis in the hope of probing the relation between growth and development of hydatid and Calcium/angiogenesis signal pathway.Methods: To evaluate efficacy of the drugs and observe the morphological changes protoscoleces(PSCs)of Echinococcus granulosus(E.g)and E.multilocularis(E.m)cultured with various drugs.Serum and organs in different period were collected from the eastablished BALB/C mice model of Echinococcosis by inoculated with E.g/E.m-PSCs after treatment with diiferent drugs.Weight of the cyst/organs were measured and the samples including serum,tissues were analysed by using ELISA,IHC-P,AFS,RT-PCR and SEM-EDX.Results: 1)In contrast to blank group,the level of calcium of mice's serum and liver decreased significantly,the expression of VEGF and CD34(an indicator of microvessel density)and hepatic collagen fibers increased obviously in control group.2)In contrast to control group,the level of calcium of mice's serum and organs including liver and lung increased significantly in verapamil(verp)group(P<0.05).Verapamil down-regulated significantly the over-expression of CAM and CAMK2 from mice's serum and organs(P<0.05).Verapamil inhibited significantly the growth and development of alveococcus in vivo and E.g-PSCs in vitro through increasing the efficacy on alveococcus and the mortality rate of E.g-PSCs(P<0.05).3)Masoprocol inhibited significantly the growth and development of hydatid in vivo and E.g-PSCs/adult in vitro through enhancing the efficacy on hydatid and the mortality rate of E.g-PSCs/adult(P<0.05).Masoprocol reduced abundantly pathological angiogenesis on the surface of E.m-metacestode.Masoprocol decreased obviously the aberrant expression of VEGF/VEGFR in the serum and VEGF/VEGFR/VEGF-mRNA in liver(P<0.05).Masoprocol inhibited significantly pathological hepatic fibrosis of host infected with E.m-PSCs.4)Apatinib significantly inhibited the growth and development of E.m-PSCs in vitro through increasing the mortality rate of E.m-PSCs(P<0.05).Conclusion: Calcium signaling pathway tightly linked with growth and development of hydatid will be an important drug-target against echinococcosis.Overactive angiogenesis signal pathway triggered by growth and development of hydatid can be inhibited by masoprocol and will be a significant target against echinococcosis.The drugs including verapamil,masoprocol and apatinib,which can inhibit growth and development of hydatid,will be candidate agents against echinococcosis.