Insulin-like Growth Factor 1 Receptor(IGF-1R) Inhibition PQ401 Anti Hydatid Of Preliminary Pharmacodynamics Research In Mice

Objective: To investigate the insulin-like growth factor 1 receptor(IGF-1R)inhibitors PQ401 anti hydatid effect in E.granulosus(E.g)and to explore the ways of its anti echinococcosis.Methods: During four days as a period time,five inhibitors(PQ401,OSI-906,GSK-690693,BEZ235 and AZD8055)interposed protoscolex of E.g,with mortality rate as indicators,with albendazole(ABZ)as the positive control drug,set series of concentration(100?mol/L,50?mol/L,25?mol/L,12.5?mol/L,6.25?mol/L),finally it was compared the different IGF-1R inhibitors anti hydatid effect and screened PQ401 appropriate concentration and time.During two days as a period time,PQ401 interposed vesicles,with collapse rate as indicators,with albendazole(ABZ)as the positive control drug,set series of concentration(50?mol/L,25?mol/L,12.5?mol/L,6.25?mol/L,3.125?mol/L),finally it was screened PQ401 lead to the vesicle collapse of concentration.Transmission electron microscope(TEM)observed PQ401 and the positive control drug interposed to vesicles ultrastructural changes.At the same time,the acute toxicity test in mice and foreign literature reference determined dose in vivo efficacy,i.p intervention for three weeks,with abendazole(ABZ)as the positive control drug,with inhibitory rate of capsules,thymus,spleen,ELISA(IL-2,IL-4,IL-10,INF-?,TNF-?),glucose and glycogen content,AST/ALT,BUN,Scr and so on as indicators to comprehensive evaluation of effect.Results: The results showed that EgPSC were interposed the PQ401 was the best in five inhibitors.PQ401 respectively appropriate concentration and time were 50?mol/L and 2d;Vesicles result showed that PQ401 leaded to the concentration of the vesicle collapse were 6.25,12.5,25,50 ?mol/L;TEM indicated that PQ401 mainly caused nuclear burst of protoscolex,nucleolus disappear,nuclear material color become deeper,heterochromatin margination phenomenon;The acute toxicity test indicated 4000mg/kg was maximum tolerated dose,and set the PQ401 dose group were 100 mg/kg,50 mg/kg;Vesicle wet weight in the PQ401 100 mg/kg dose group and model group was significantly(P<0.05);Q401 100 mg/kg,50 mg/kg dose group,ABZ group the inhibitory rate of capsules respectively 53.20%,40.45%,57.08%;Dose groups of glucose content was the minimum,while glycogen content was relatively high;PQ401 100 mg/kg dose group and model group was significantly(P<0.05);Thymus was not significantly in all groups(P>0.05);Spleen in PQ401 100 mg/kg dose group and ABZ group was significantly(P<0.05);Dose groups of IL-2,INF-? and TNF-? were elevated than model group and control group,while IL-4 and IL-10 reduced;HE and Liver,kidney function indicated that tissues damage PQ401 than ABZ lighter.At the same time,PQ401 was damaged to larva vesicles.Conclusion: PQ401 anti hydatid was the best in the five kinds of inhibitors,PQ401 own anti EgPSC and vesicles fountion in vitro.we found it had a dependent relationship with time and dose.PQ401 also can anti EgPSC in vivo.It may interference model mice spines ball larva organization transformation between glucose and glycogen and immunological methods to achieve anti echinococcosis.