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无环核苷9-(1,3-二羟基-2-丙氧甲基)鸟嘌呤与γ干扰素联合应用对小鼠2型单纯疱疹病毒的增效作用。

Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with gamma interferon against herpes simplex virus type 2 in mice.

作者信息

Fraser-Smith E B, Eppstein D A, Marsh Y V, Matthews T R

出版信息

Antiviral Res. 1985 Jun;5(3):137-44. doi: 10.1016/0166-3542(85)90046-4.

DOI:10.1016/0166-3542(85)90046-4
PMID:2992368
Abstract

The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) and recombinant mouse interferon gamma (rMuIFN-gamma) were evaluated for their efficacy alone and in combination against a herpes simplex virus type 2 systemic infection in mice. Intraperitoneally infected animals were treated once a day with the drugs at various concentrations for 5 days starting 24 h after inoculation. DHPG was given subcutaneously and rMuIFN-gamma intraperitoneally. For DHPG, the effective dose at which 50% of the mice survived (ED50 was lowered approximately 10-fold from 3.4 to 0.25 mg/kg when given in combination with an ineffective dose of 4MuIFN-gamma (10(3) units per mouse). For rMuIFN-gamma, the ED50 was lowered greater than 10-fold from 6 x 10(3) to less than 3 x 10(2) units per mouse when given in combination with a marginally effective dose of DHPG (1 mg/kg). Construction of an isobologram and calculation of the corresponding fractional protective dose index (less than 0.12 where values less than or equal to 0.5 are considered synergistic) indicates an enhanced protective interaction by the combination of the two drugs.

摘要

对无环核苷9-(1,3 -二羟基-2-丙氧甲基)鸟嘌呤(DHPG)和重组小鼠干扰素γ(rMuIFN-γ)单独及联合使用对小鼠2型单纯疱疹病毒全身感染的疗效进行了评估。腹腔感染的动物在接种后24小时开始,每天用不同浓度的药物治疗一次,持续5天。DHPG皮下给药,rMuIFN-γ腹腔给药。对于DHPG,当与无效剂量的4MuIFN-γ(每只小鼠10³单位)联合使用时,使50%的小鼠存活的有效剂量(ED50)从3.4毫克/千克降低了约10倍,至0.25毫克/千克。对于rMuIFN-γ,当与边缘有效剂量的DHPG(1毫克/千克)联合使用时,ED50从每只小鼠6×10³单位降低了超过10倍,至小于3×10²单位。构建等效线图并计算相应的分数保护剂量指数(值小于或等于0.5时,小于0.12被认为具有协同作用)表明两种药物联合使用具有增强的保护作用。

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