外用联合靶向siRNA治疗生殖器疱疹豚鼠模型实验

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（siN.C），作用4小时后给予疱疹病毒2型（HSV-2）野生株接种，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siN.C制剂，每周1次至皮损愈合。2个月后腹腔内注射环磷酰胺并给予紫外线照射诱导复发，计算疱疹复发率及HSV-2培养阳性率。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GH复发。

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

Objective:To assess the effect of combined targeting siRNA ( CT-siRNA, HSV-2 UL27. 2 gene 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 siN.C. After 4 hours, the herpes virus type 2 (HSV-2) wild strains were inoculated to vagi-na 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 siN.C, once a week until lesion healing. All guinea pigs were treated with intraperitoneal injections of cyclophosphamide and ultra-violet radiation to induce the recurrence after the 2 month treatment and the recurrence rate was assessed. Re-sults: 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.