抗乙肝药物ZY101对HBV转基因鼠体内抗病毒作用研究

Antiviral effectivity of anti-hepatitis B drug ZY101 on HBV transgenic mice

目的:观察ZY101在HBV转基因BALB/c小鼠体内的抗HBV作用。方法:将30只雄性HBV转基因鼠随机分为阴性对照组(杜氏磷酸盐缓冲液,DPBS)、阳性对照组(每天一次灌胃给予拉米夫定150mg·kg-1)、ZY101低剂量组(1mg·kg-1)、ZY101中剂量组(3mg·kg-1)和ZY101高剂量组(10mg·kg-1),每组6只,阳性对照组每天一次灌胃给药,其他组单次尾静脉注射。药前、药后后1、2、3、4、5、6、7、8、10、12、14、16、18、20、22、24、26、28、30、32、34、36、38 w采集血清,用ELISA试剂盒检测HBsAg、HBeAg的表达,用实时荧光定量PCR技术检测血清中HBV DNA的含量。药后38w处死所有动物,采集肝组织,检测肝组织中HBsAg和HBeAg表达及HBV DNA和RNA的含量。结果:拉米夫定每天灌胃给予HBV转基因小鼠150mg·kg-1能够明显降低血清HBV DNA水平(P<0.05),但对HBsAg、HBeAg和HBV RNA无明显影响;ZY101分别单次尾静脉注射给予HBV转基因小鼠1、3、10mg·kg-1,能够降低血清及肝组织中HBsAg和HBeAg的水平(P<0.05、P<0.05、P<0.01),且有剂量依赖性,但血清HBV DNA及肝组织HBV DNA、HBV RNA水平无显著影响。结论:在本实验条件下,拉米夫定每天灌胃给予HBV转基因小鼠150mg·kg-1能够降低血清HBV DNA水平;ZY101单次尾静脉注射给予HBV转基因小鼠1、3、10mg·kg-1,能够剂量依赖的降低HBsAg和HBeAg的表达水平。

Objective. To observe the anti-HBV effectivity of ZY101 in HBV transgenic BALB/c mice by a single i.v. dose. Meth- ods. Thirty male HBV transgenic mice were randomly divided into negative control group（DPBS）, positive control group（lamivudine 150 mg · kg^-1 , once a day p. o. ）, ZY101 low dose group（1 mg · kg^-1 ）, ZY101 middle dose group（3 mg· kg^-1 ） and ZY101 high dose group（10 mg · kg^-1）, 6 animals per group. Negative group and ZY101 groups were once intravenous infused. Serum was col- lected before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 30, 32, 34, 36, 38 weeks after infusion, and the commercial ELISA kit was used to assess the expression of HBsAg and HBeAg, the real-time fluorescent quantitative PCR method was used to assess the contents of serum HBV DNA and HBV RNA. Liver tissue was collected 38 weeks after administration and HBsAg, HBeAg, and HBV DNA were assessed. Results. Lamivudine（150 mg · kg^-1 , qd, p. o. ） can significantly reduce the HBV DNA level in serum in HBV transgenic mice（P〈0.05）, but have no impact on the expression of HBsAg, HBeAg and HBV RNA. After a single intravenous infusion of ZY101 at the dosage of 1, 3, 10 mg · kg^-1 , the expression level of HBsAg and HBeAg in ser- um and liver tissue were dose dependently reduced（P〈0. 05）, but HBV DNA and HBV RNA level were not significantly impacted（P 〈0. 05）. Conclusion.. Under this experimental condition, lamivudine（150 mg· kg^-1 , once a day, p. o. ） can reduce serum HBV DNA level of HBV transgenic mice, while ZY101 （1-10mg · kg^-1 , single dose, i. v. ） can dose dependently reduce the expression of HBsAg and HBeAg in serum and liver tissue.