阿昔洛韦联合羟基脲抗疱疹病毒的研究  

Hydroxyurea potentiates the anti-herpes virus activities of acyclovir

作　　者：杨红[1] 陶佩珍[2] 

机构地区：[1]首都医科大学燕京医学院药学系,北京101300 [2]中国医学科学院中国协和医科大学医药生物技术研究所,北京100050

出　　处：《华西药学杂志》2005年第5期401-404,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的研究抗肿瘤药物羟基脲(HU)与抗病毒药物阿昔洛韦(ACV)联用抗疱疹病毒的协同增效作用。方法体外实验应用VERO细胞培养法及MTT染色法进行实验,以Calcusyn软件计算、分析实验结果;体内实验采用单纯疱疹病毒I型感染的兔角膜炎实验模型,用临床裂隙灯观察不同用药情况下兔角膜病变,进行Trouzdale评分,并分离病毒、滴定度及病理检查。结果体外实验结果显示ACV∶HU为1∶312.5及1∶100时,两药为协同作用;ACV∶HU为1∶50、1∶25、1∶10时,两药为拮抗作用。配比为1∶300的阿昔洛韦和羟基脲联合治疗病毒性角膜炎,其疗效与0.1%的ACV相当。结论羟基脲对阿昔洛韦抗HSV-I活性在一定比例条件下,体内、外均有增效作用。OBJECTIVE To study the potentiating effects of hydroxyurea （HU）, a classical anti - tumor drug,on the anti - herpes simplex virus （HSV） type Ⅰ activities of acyclovir （ACV） in viVo and in vitro. METHODS The current study examined the effects of different ratio comb/nations of ACV and HU （1：10, 1：25. 1：50, 1：100, 1：312.5） on anti - HSV- Ⅰ activities in vitro by Vero cell and MTT assay; The combination treatment efficacy of ACV and HU （combination ratio 1：300） in vivo against the HSV-I keratitis of New Zealand white rabbits was evaluated by keratopathy （Trouzdale scale ）,virus isolation and pathological examination.RESULTS In vitro results showed that when the combination ratios of ACV：HU were 1：312.5 and 1 ： 100, they displayed significantly synergistic profiles with the reductions of ACV ED50 by 18.3 and 4.3 fold respectively, while combination ratios of 1：50, 1：25 and 1：10 showed antagonistic profiles. From the standards of corneal epithelial lesion scores and viral titers, the treatment efficacy of ACV ＋ HU （ 1：300, ACV 0.88 mmol. ml^ -1 and HU 264 mmol. ml^ -1 ） was comparable with ACV group （0.1% ACV drop） （P〉0.05）.CONCLUSION The results in vitro and in vivo showedthat thepotentiating effects of HU on anti - HSV - Ⅰ activities of ACV depended on the ratio of ACV and HU. The relevance of the results for the potential chnical use has been discussed.

关 键 词：羟基脲 阿昔洛韦 单纯疱疹性角膜炎 单纯疱疹病毒 抗病毒药物 

分 类 号：R96[医药卫生—药理学]