Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata

AIM： To evaluate the antiviral effect of the effective ingredient of Styela plicata in a murine model of hepatitis B virus carrier. METHODS： HBV-transgenic mice were divided into 3 groups （control group, lamivudine treatment group and the effective ingredient of Styela plicata treatment group） and assigned to receive normal diet, lamivudine or the effective ingredient of Styela plicata for consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme-linked immunosorbent assay （ELISA） method. Serum HBV DNA was detected by real-time polymerase chain reaction （RT-PCR）. Serum T helper （h） 1 cytokine interleukin （IL）-2 and Th2 cytokine IL-6 were detected by the quantitative sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was assigned to receive the effective ingredient of Styela plicata for consecutive weeks. The histology of liver tissue was evaluated before and after treatment. RESULTS： Twelve weeks after starting the therapy, serum hepatitis B surface antigen was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet （F12wk = 88.81, P12wk = 0.000 〈 0.01）. Serum HBV DNA was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet （F12wk = 20.71, P12wk = 0.000 〈 0.01）. However, like lamivudine, the effective ingredient of Styela plicata could not inhibit the replication of HBV completely. A rebound phenomenon of hepatitis B surface antigen and HBV DNA in sera could be found 4 wk after withdrawal of medication. Eight weeks after starting the therapy, serum levels before and after Styela plicata treatment of IL-2 were 2.41 ± 0.38 and 10.56 ± 0.78 ng/L, respectively （t8wk = -16.51, P8wk = 0.000 〈 0.01）. Compared with the serum levels of IL-2 in the normal diet-treated mice （2.48 ± 0.17 ng/L; t8wk = 13.23, P8wk = 0.000 〈 0.01）. Serum levels before and after Styela plicata treatment of IL-6 were 63.62 ± 6.31 and 54.52 ± 6.22 ng/L, respectively, compared with the serum levels of IL-6 in the normal diet-treated mice （60.84 ± 4.21 ng/L）. Histological analysis of liver from Styela plicata-treated HBV-transgenic mice also showed catabatic status in inflammation and hepatitis B surface antigen. CONCLUSION： Styela plicata may be an effective anviral medicine in treating chronic hepatitis B.

瞄准：在肝炎 B 搬运人的一个鼠科的模型评估 Styela plicata 的有效成分的抗病毒的效果。方法：HBV 转基因的老鼠被划分成 3 个组(控制组， lamivudine 处理组和 Styela plicata 处理组的有效成分) 并且分配了收到正常饮食， lamivudine 或 Styela plicata 的有效成分连续星期。浆液肝炎 B 表面抗原被连接酶的免疫检测吸着剂试金(ELISA ) 方法。浆液 HBV DNA 被即时聚合酶链反应(RT-PCR ) 检测。浆液 T 助手(h) 1 cytokine interleukin (IL )-2 和 Th2 cytokine IL-6 被量的三明治酶免疫分析技术检测。另一组 HBV 转基因的老鼠被分配收到 Styela plicata 的有效成分连续星期。肝组织的组织学在治疗前后被评估。结果：12 个星期在开始治疗以后，浆液肝炎 B 表面抗原显著地在 Styela plicata 被降低与收到正常饮食的老鼠相比对待老鼠和对待 lamivudine 的老鼠(F (12wk )= 88.81， P (12wk )= 0.000 <0.01 ) 。浆液 HBV DNA 显著地在 Styela plicata 被降低与收到正常饮食的老鼠相比对待老鼠和对待 lamivudine 的老鼠(F (12wk )= 20.71， P (12wk )= 0.000 <0.01 ) 。然而， Styela plicata 的有效成分象 lamivudine 一样，不能完全禁止 HBV 的复制。在重量的单位的肝炎 B 表面抗原和 HBV DNA 的回缩现象一 could 在药的退却以后被发现 4 wk。八个星期在开始治疗以后，在 IL-2 的 Styela plicata 处理前后的浆液层次是 2.41 +/- 0.38 和 10.56 +/- 0.78 ng/L，分别地(t (8wk )=-16.51, P (8wk )= 0.000 <0.01 ) 。与在正常对待食谱的老鼠的 IL-2 的浆液层次相比(2.48+/-0.17 ng/L；t (8wk )= 13.23， P (8wk )= 0.000 <0.01 ) 。在 IL-6 的 Styela plicata 处理前后的浆液层次是 63.62 +/- 分别地， 6.22 ng/L 在正常对待食谱的老鼠 IL-6 与浆液相比铺平的 6.31 和 54.52 +/-(60.84 +/- 4.21 ng/L ) 。从 Styela 对待 plicata 的 HBV 转基因的老鼠的肝的组织学的分析也在发炎和肝炎 B 表面抗原显示出下降地位。结论：Styela plicata 可以是在对待长期的肝炎 B 的有效的抗病毒的药。