去氢骆驼蓬碱衍生物1-(2-氯)苯基-9-丁基-β-咔啉对小鼠细粒棘球蚴病的影响

Effects of 1-( 2-chlorine )-phenyl-9-butyl-β – carboline on cystic echinococcosis in mice in vivo

目的研究去氢骆驼蓬碱衍生物1-(2-氯)苯基-9-丁基-β-咔啉(DH-330)对小鼠细粒棘球蚴病的作用。方法昆明小鼠腹腔注射原头节继发感染8个月制备细粒棘球蚴病小鼠模型。按照体质量将造模成功小鼠随机分为6组:模型组、对照1组、对照2组和低、中、高3个剂量实验组,每组10只。模型组给予蒸馏水;对照1组给予50 mg·kg^(-1)阿苯达唑;对照2组给予50 mg·kg^(-1)去氢骆驼蓬碱;低、中、高3个剂量实验组分别给予25,50,100 mg·kg^(-1)DH-330。灌胃给药8周后,解剖小鼠取囊泡,比较各组间囊湿重差异;透射电镜观察囊泡超微结构变化;用苏木精-伊红染色法观察囊泡、肝病理组织学变化。结果模型组、对照1组、对照2组和低、中、高3个剂量实验组小鼠的嚢湿重分别为(34.38±4.32),(11.38±2.37),(15.89±1.31),(16.22±2.30)(11.69±2.95)和(9.78±1.14)g,与模型组相比,各给药组均可显著降低囊湿重,差异均有统计学意义(均P<0.05);与去氢骆驼蓬碱相比,高剂量实验组可明显降低囊湿重,差异有统计学意义(P<0.05)。除模型组和低剂量实验组外,其余各组均能够破坏包虫细胞核,导致细胞裂解、核仁消失。实验组能够不同程度的改善肝和囊泡组织中炎细胞浸润情况。结论DH-330能够降低细粒棘球蚴病小鼠的囊湿重,抑制小鼠体内包虫生长,并能改善肝和囊泡的炎症,显示出良好的抗细粒棘球蚴作用,或可能成为一种有效的抗包虫病新药。

Objective To evaluate the in vivo treatment efficacy o harmine derivative 1-(2-chloro) phenyl-9-butyl-β-carboline(DH-330) on mice cystic echinococcosis (CE).Methods Kunming mice were injected intraperitoneally into the protoscoleces and infected with secondary infection for 8 months to prepare CE model.The successfully modeled mice were randomly divided into 6 groups according to their body weight:model group,control-1,-2 groups and experimental-L,-M,-H groups,with 10 mice in each group.The model group was given distilled water and control-1,-2 groups were given 50 mg·kg^(-1)albendazole and harmine,respectively.The experimental-L,-M,-H groups were given 25,50,100 mg·kg^(-1)DH-330.After 8 weeks of intragastric administration,the mice were dissected and vesicles were taken,and the differences of cyst weight were compared.The ultrastructure changes of cysts were observed by transmission electron microscope (TEM).The histopathology of cysts and liver were observed by hematoxylin-eosin(HE) staining method.Results The cyst weight of model group,control-1,-2 groups and experimental-L,-M,-H groups were (34.38±4.32),(11.38±2.37),(15.89±1.31),(16.22±2.30),(11.69±2.95) and(9.78±1.14) g,respectively.Compared between drugs group and model group,the difference was significant (all P<0.05);compared between experimental-H group and harmine group,the difference was significant(P<0.05).Except for the model group and experimental-L group,all other groups can damage the hydatid nuclei,which lead to cell lysis and nucleoli disappear.Experimental groups can improve inflammatory cells infiltration in liver and vesicle.Conclusion DH-330 can reduce the cysts weight of CE mice,inhibit the growth of hydatid,and improve the inflammation of the liver and vesicles,showing a good anti-E.granulosus effect,or may become an effective antihydatid disease new drug.