Drug resistance induction and analysis of differential expression protein on adult Schistosoma j aponicum induced by ED50 PZQ / 中国人兽共患病学报

ABSTRACT

ABSTRACTIn the present study ,we aimed to identify differentially expressed proteins between induced worms (the infec‐ted mice were treated intragastrically with ED50 PZQ) and uninduced worms (control group) for clarifying the mechanism of PZQ .ED50 PZQ was used to administrate mice that were infected with S .japonicum via intragastric incubation for consecutive‐ly 30 days .Twenty‐one days later ,mice were sacrificed after treatment with 200 mg/kg PZQ for continuously five days ,and the male worms were obtained and some of them were subjected in DMEM medium with different concentrations of PZQ in vitro for 16 hours .Then the worms were washed twice and incubated in PZQ‐free medium for 72 hours .Compared with control group ,the induced worms had lesser sensitivity to PZQ .The survival rate of induced worms was 75 .6% in vitro when the con‐centration of PZQ was 112 mol/L (the concentration was 8 times of uninduced worms Lethal Concentration ) ,significantly higher than that in the uninduced worms (11 .1% ,P<0 .05) ,showing obviously tolerance .The other induced and uninduced worms were acquired and collected for 2D‐DIGE and MALDI‐TOF‐MS ,and combined with bioinformatics to analyse the func‐tion of the identified protein .Thirty differential expression proteins were confirmed between induced and uninduced worms ,in‐cluding 12 proteins up‐regulated and 18 proteins down‐regulated .These proteins respectively ascribed to cytoskeleton‐associat‐ed protein ,glucose and energy metabolism enzymes ,stress proteins ,thioredoxin peroxidase enzymes ,and other protease .Up‐or down‐regulation of these differential proteins indicated that PZQ promote or inhibit the expression of some specific genes . These findings may help to clarify the mechanism of PZQ ,simultaneously ,providing a scientific basis for exploring new vaccine candidate antigens and targets for drug therapy .