Preliminary Study On The Inhibitory Effect And Mechanism Of JQ1 On The Reproductive System Of Schistosoma Japonicum

Objective Schistosoma japonicum eggs are the pathogenic factor of schistosomiasis,and inhibiting the development of the reproductive system of schistosomiasis is an effective measure to reduce the production of schistosomiasis eggs.Small molecular compound JQ1 is an inhibitor of BET protein family.However,little is known about the role of JQ1 in the development of the reproductive system of Schistosoma japonicum.So in this study,We studied the role of JQ1 in the reproductive system of Schistosoma japonicum and its effect on oviposition,and preliminarily discussed the mechanism of JQ1 inhibiting its reproductive system,so as to lay a foundation for the prevention and control of Schistosoma japonicum epidemic.Methods Four weeks after infection with cercariae of Schistosoma japonicum,Schistosoma japonicum was cultured with 5 ?M,10 ?M and 15 ?M JQ1 for 10 days to collect Schistosoma japonicum and eggs.The morphological changes of reproductive system structure of Schistosoma japonicum were observed by laser confocal scanning,the proliferation of female and male germ cells of Schistosoma japonicum treated with JQ1 were detected by Ed U method,the eggs were counted and the activity of eggs was observed by acridine orange staining.The expression of reproductive related genes Sj Plk1,Sj Nanos1 and Sj Brd2 of Schistosoma japonicum was detected by q PCR.C57/BL6 mice were infected with Schistosoma japonicum cercariae with 18 ±2 cercariae,8 mice in each group.4 weeks after infection,the mice in the treatment group were injected intraperitoneally with JQ1(50 mg/kg/d)every day,and the mice in the control group were injected intraperitoneally with 10% ?-cyclodextrin every day for 15 days.The liver of mice in the solvent control group and the JQ1 treatment group were compared.The size of granuloma was detected by HE method,the number of eggs in the liver was counted,the morphological changes of eggs were observed,and the content of serum transaminase was measured.The changes of reproductive system and germ cell proliferation of Schistosoma japonicum were detected by laser confocal.Results The in vitro experiment showed that there was no significant difference between the viability and the logarithm of Schistosoma japonicum in JQ1 treated group,but the number of eggs produced decreased significantly,the activity of eggs in JQ1 treated group decreased significantly by acridine orange staining,and the number of proliferated cells in JQ1 treated group decreased with the increase of dose,in which the testes of males and ovaries and yolk glands of females changed most obviously.Laser confocal observation showed that the gap between ovaries of female worms widened,the testes of male worms also appeared wrinkles and gaps,and the number of sperm in seminal vesicles decreased in JQ1 group.At the same time,we detected the expression of reproductive related genes Sj Plk1,Sj Nanos1 and Sj Brd2 of Schistosoma japonicum,and found that the expression of these genes decreased in JQ1 treatment group.We used JQ1 to treat C57/BL6 mice infected with Schistosoma japonicum.The white granulomatous nodule spots on the surface of the liver and the weight of the liver decreased significantly in the JQ1 treatment group.It was found that the number of liver eggs decreased in the JQ1 treatment group,but had no effect on the number of adult Schistosoma japonicum and the percentage of pairing.HE staining showed that the area of liver granuloma in JQ1 treatment group decreased significantly(P <0.05).The activities of AST and ALT in serum of mice treated with JQ1 were significantly decreased(P < 0.05).Conclusion Through in vitro experiments,we found that JQ1 could inhibit the oviposition of Schistosoma japonicum and the proliferation of female and male germ cells,lead to changes in the structure of reproductive system,and down-regulate the expression of genes Sj Plk1,Sj Nanos1 and Sj Brd2.Through in vivo experiments,we found that JQ1 treatment inhibited liver granuloma induced by eggs.Therefore,we found that JQ1 can inhibit the development of the reproductive system of Schistosoma japonicum,affect the production of eggs,thus reduce the pathogenicity and epidemic of Schistosoma japonicum,and lay a foundation for further research and development of specific inhibitors against the reproductive system of Schistosoma japonicum.