脂酰辅酶A合成酶抑制剂Triacsin C对弓形虫速殖子体内增殖抑制效果的观察

Inhibitory effect of Triacsin C,an inhibitor of Acyl-CoA synthetase,on the proliferation of Toxoplasma gondii tachyzoites in vivo

为明确脂酰辅酶A合成酶抑制剂Triacsin C对弓形虫速殖子是否具有体内抑制效果,本试验将不同质量浓度的Triacsin C灌服小鼠,并以磺胺嘧啶和阿奇霉素作为参考,后将弓形虫RH株速殖子(2×10^(5)个)腹腔感染给药组小鼠,以小鼠的存活时间、腹腔中速殖子数量、肝脏中弓形虫核酸的拷贝数和主要脏器的病理损伤作为指标,观察Triacsin C对弓形虫的体内抑制效果;同时对不同药物质量浓度下不感染弓形虫的小鼠进行组织病理学观察。结果显示,8×10^(-2)g/L Triacsin C能够显著抑制速殖子的增殖,小鼠的存活时间也相应延长,低剂量下(1×10^(-2),2×10^(-2)g/L)抑制效果不显著,感染组小鼠肝、脾、肺、肾均出现明显的病理损伤,并在192 h内死亡;给药未感染弓形虫的小鼠脏器未见有明显病理变化。结果表明,高剂量的Triacsin C具有体内抑制弓形虫速殖子增殖的能力,且对宿主主要脏器不产生病理损伤。

In order to determine whether Triacsin C,an inhibitor of Acyl-CoA synthase,has an inhibitory effect on Toxoplasma gondii(T.gondii)tachyzoites in vivo,different concentrations of Triacsin C were administered to mice,while sulfadiazine and azithromycin were used as references.After that,2×10^(5)tachyzoites of RH strain were inoculated with each mouse by intraperitoneal route in the infection groups.The survival time,number of tachyzoites in the abdominal cavity,copy number of T.gondii nucleic acid in the liver and the pathological damage of main organs were selected as mainly indicators.Meanwhile,the histopathological observations of mice in the uninfected groups but under different drug concentrations were also carried out.The results showed that 8×10^(-2)g/L Triacsin C could significantly inhibit the proliferation of tachyzoites and prolong the survival time of mice.However,the inhibitory effects were not significant at low doses(1×10^(-2)g/L and 2×10^(-2)g/L)when compared with the control group.The mice in the infection groups had obvious pathological damage in the liver,spleen,lung and kidney,and died within 192 h.No pathological changes were found in the organs of uninfected mice.In summary,this work revealed that high-dose Triacsin C had the ability to inhibit the proliferation of T.gondii tachyzoites in vivo,and did not cause pathological damage to the main organs of the host.