白藜芦醇在联合治疗鼠艾滋病中可能的增效作用研究

The Potential Synergistic Activity of Resveratrol Development in Combination Therapy of the Murine AIDS

白藜芦醇(resveratrol,Res.)是一种潜在的抗HIV药物,在体外与AZT、3Tc、ddI等核苷类抗病毒药物联用时表现出很强的协同增强作用。在本篇论文中我们在Friend-MuLV病毒感染的BALB/c鼠艾滋病模型(MAIDS)上研究了用白藜芦醇、AZT、3Tc不同组方及白藜芦醇单独使用治疗后的抗逆转录病毒作用,分析白藜芦醇在联合治疗中可能的潜在协同增强作用。72只BALB/c小鼠随机分成9组(每组8只):正常对照组(未感染和未治疗),病毒对照组(感染但未治疗)和7个其他药物治疗组(感染病毒后并用白藜芦醇、AZT、3Tc不同组方治疗)。药物通过口服给药方式在病毒感染4 h后给药,每天一次,每周7 d,持续3周。感染后3周,所有实验组处死,对表现疾病病理特征的一些指标进行检测评价。结果表明:在体内鼠艾滋病模型上,单独运用白藜芦醇仅仅只有部分能够减少疾病的进展,未表现出所预期的显著的抗逆转录病毒作用(只有20.78%的脾肿抑制率)。白藜芦醇和AZT3、Tc的联合用药有较好的抗病毒效果(减少白细胞数83.34%,脾肿抑制率91.79%,升高CD4+/CD8+比值等)。然而,这些结果与AZT和3Tc联合给药的结果是重叠的,AZT和3Tc联合给药有类似的结果(脾肿抑制率87.65%和白细胞数减少82.25%),排除了AZT3、Tc和白藜芦醇可能的协同增效作用。因此在MAIDS模型中白藜芦醇和AZT3、Tc之间没有协同作用,AZT、3Tc并不会因为和白藜芦醇的联用而提高抗病毒效果。

Resvemtrol （3,4,5＇-erihydroxystilbene, Res. ） is a highly potential and selective antiretroviral nature product. The Res.has shown a strong synergistic anti-HIV activity in combination with nucleoside analogues in vitro .It is possible that during combination therapy, drug interaction may arise in vivo that would influence their anfiviral activity. To investigate in vivo Res. synergistic anfiretroviral activity in combination with nucleoside analogues, experiments involving combination of Res., AZT and 3Tc,were performed in a routine model of immunodeficiency （MAIDS）, an AIDS-like disease caused by the Friend-MuLV retroviral in susceptible BALB/c mice. Subsequently, the antiretroviral activity of AZT and/or 3Tc plus Res. in the MAIDS was evaluated and compared with AZT and 3Tc or Res., administered as single drug. The results obtained showed that Res. did not show markedly antiviral activity. Weak potential antiretroviral was suggested only at a dose of 100 mg/kg body weight （20.78% splenomegaly reduction）. Res. in combination with AZT and 3Tc is able to reduce WBC count （83.34%）, splenomegaly （91.70%）, and upgrade CD4^＋/CD8^＋ values. However, upon AZT plus 3Tc administration, similar result was obtained （ WBC count and splenomegaly reduction）. Furthermore, These results ovedapped those obtained upon AZT plus 3Tc administration （87.5% splenomegaly and 82.25% WBC count reduction） .Thus despite strong synergistic anti-HIV activity alone or in combination with nucleoside analogues in vitro, no synergy between Res. plus AZT or 3Tc was observed in Friend-MAIDS and administration of AZT and 3Tc does not improve the antiviral results obtained by Res. administration.