外用联合靶向siRNA治疗生殖器疱疹豚鼠模型实验

Effect of topical combined targeting siRNA on guinea pig with genital herpes

目的:评价联合靶向特异性小干扰RNA(HSV-2 UL27.2和UL29.2基因)对生殖器疱疹(GH)模型的疗效。方法:(1)病毒攻击实验:雌性豚鼠60只,随机分为治疗组和对照组,每组30只,治疗组小鼠外阴和阴道内外用联合靶向特异性小干扰RNA(CT-siRNA),对照组外用非靶向基因的RNA制剂(si N.C),作用4小时后接种疱疹病毒2型(HSV-2)野生株,观察豚鼠发病情况并计算生存率。(2)选取接种HSV-2后具有初发GH反应的雌性豚鼠60只,分为治疗组和对照组,每组30只,分别外用CT-siRNA和si N.C制剂,每周1次至皮损愈合。2个月后小鼠腹腔内注射环磷酰胺并给予紫外线照射诱导复发,计算疱疹复发率。结果:病毒攻击感染后治疗组存活率(80.0%)高于对照组(23.3%)(P<0.05)。治疗第10天治疗组皮损积分值(0.25±0.25)较对照组明显降低(1.0±1.25)(P<0.05)。诱导复发后,治疗组复发率(16.7%)低于对照组(60.0%)(P<0.05)。结论:外用CT-siRNA制剂能预防HSV-2的感染及复发。

Objective： To assess the effect of combined targeting siRNA（ CT- siRNA,HSV- 2 UL27. 2gene combined UL29. 2 gene） on genital herpes of guinea pig. Methods：（ 1） HSV- 2 infection experiment：sixty guinea pigs were divided into the treatment group and control group（ 30 in each group）. Guinea pigs in the treatment group were treated with topical CT- siRNA on vulva and vagina and those in the control group were treated with si N. C. After 4 hours,the herpes virus type 2（ HSV- 2） wild strains were inoculated to vagina in all the guinea pigs.（ 2） Sixty guinea pig models with the infection of genital herpes were divided into the treatment group and control group（ 30 guinea pigs in each group）. Guinea pigs in the treatment group were treated with topical CT- siRNA on vagina and those in the control group were treated with si N. C,once a week until lesion healing. All guinea pigs were treated with intraperitoneal injections of cyclophosphamide and ultraviolet radiation to induce the recurrence after the 2 month treatment and the recurrence rate was assessed.Results： The survival rate in the treatment group was 80%,which was higher than that in the control group（ 23. 3%）,（ P〈0. 05）. At day 10 of the treatment,the lesions score in the treatment group was（ 0. 25 ±0. 25）,which was lower than that in the control group（ 1. 0 ± 1. 25）（ P〈0. 05）. The recurrence rate in the treatment group was 16. 7%,which was lower than that in the control group（ 60%）,（ P〈0. 05）.Conclusion： Topical CT- siRNA can reduce the infection rate and recurrence of HSV- 2.