两种马蹄金素衍生物体内抗HBV药效学研究

Study of in vivo anti-hepatitis B activity of two Matijin-su derivatives

目的:比较两种马蹄金素衍生物的体内抗HBV活性。方法:通过高压尾静脉注射pAAV-HBV1.2质粒进入C57BL/6J小鼠体内的方法,建立慢性HBV感染的小鼠模型;选取建模成功的小鼠,随机分为4组,即阴性对照组、阳性对照组和马蹄金素衍生物-1组、-2组,每组10只,分别腹腔注射200μL体积的PBS、阳性药物Birinapant 30 mg/kg、马蹄金素衍生物-1和-2(均为20 mg/kg),每周给药1次,连续给药4周。观察各组治疗前后的抗HBV病毒效果,并进行治疗后肝组织病理形态检测。结果:治疗后,马蹄金素衍生物1组和马蹄金素衍生物2组血清中HBsAg、HBeAg、AST和ALT显著性下降(P<0.05);与阳性对照组相比较,下降程度无明显区别(P>0.05);肝组织病理对比,各组间无显著区别。结论:马蹄金素衍生物具有一定的体内抗HBV作用。

Objective:To investigate and evaluate the anti-HBV activity of two kings of Matijin-su in vivo.Methods:Chronic HBV infection was established in C57BL/6J mice by injecting pAAV-HBV1.2 plasmid into high pressure caudal vein.Mice successfully modeled w.ere randomly divided into 4 groups,namely negative control group,positive control group,Matijin-su derivatives-1 group and Matijin-su derivatives-2 group,with 10 mice in each group.They were intraperitoneally injected with 200μL volume of PBS,positive drug Birinapant 30 mg/kg,Matijin-su derivatives-1(20 mg/kg)and Matijin-su derivatives-2(20 mg/kg),respectively.Dosing was given once a week for 4 weeks.The anti-HBV effects of each group were observed before and after treatment,and the pathological morphology of liver tissue was detected after treatment.Results:After treatment,the serum levels of HBsAg,HBeAg,AST and ALT in group 1 and group 2 decreased significantly(P<0.05).Compared with the positive control group,there was no significant difference in the degree of decline(P>0.05).Histopathological comparison of liver tissue showed no significant difference among the groups.Conclusion:Matijin-su derivatives have some anti-HBV effects in vivo.