中国麻风皮肤病杂志 ›› 2016, Vol. 32 ›› Issue (2): 88-92.

• 论著 • 上一篇    下一篇

外用联合靶向siRNA治疗生殖器疱疹豚鼠模型实验

李淑林1,*,韩建德1 ,廖绮曼1 ,李 欢1 ,李茵茵2 李红梅2, 马春光1, 陈木开 1   

  1. 1.中山大学附属第一医院皮肤科，广州，510080 2.中山大学有害生物防治国家重点实验室，广州，510080
  • 出版日期:2016-02-15 发布日期:2018-12-18
  • 通讯作者: 深圳中山泌尿外科医院皮肤科，深圳，518000

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

LI Shulin1,2, HAN Jiande1, LIAO Qiman1, LI Huan1, LI Yinyin3, LI Hongme3, MA Chunguang1, CHEN Mukai1   

  1. 1.Department of Dermatology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080，China； Department of Dermatology, Shenzhen Zhongshan Uropoiesis Surgical Hospital，Shenzhen 518000, China; 2. State Key Laboratory of Sun Yat-sen University Pest Management, Guangzhou 510080, China
  • Online:2016-02-15 Published:2018-12-18
  • Contact: CHEN Mukai, E-mail: ytchen2008@gmail.com

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摘要： 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。

关键词: 小干扰RNA, 生殖器疱疹, 动物模型

Abstract: Objective: To assess the effect of combined targeting siRNA (CT-siRNA, HSV-2 UL27.2 gene combined UL29.2 gene) on guinea pig with genital herpes. 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 CT-siRNA on vulva and vagina and guinea pigs in the control group were treated with not targeting any gene control RNA (siN.C) on vulva and vagina. After 4 hours, the herpes virus type 2 (HSV-2) wild strains were inoculated to vagina in all the guinea pigs. The incidence, mortality and positivity rate of HSV-2 culture of vaginal secretions were assessed. (2) Sixty guinea pig models with HSV-2 and 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 CT-siRNA on vagina and those in the control group were treated with siN.C on vagina, once a week until lesion healing. All guinea pigs were treated with intraperitoneal injections of cyclophosphamide and ultraviolet radiation to induce the recurrence of GH 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 inflammation of HSV-2 and recurrence of GH.

Key words: siRNA, genital herpes, animal mode