目的 研究椿乳凝胶抗低危型人乳头瘤病毒（human papillomavirus，HPV）的作用。方法 建立低危型HPV6、HPV11假病毒感染人胚肾293FT细胞模型，评价椿乳凝胶对HPV感染能力及对细胞周期的影响。将HPV6、HPV11假病毒注入苯甲酸雌二醇预处理的雌性小鼠阴道内建立HPV感染动物模型，病毒感染48 h后检测病毒定植情况，将定植成功的小鼠模型随机分为模型组、鬼臼毒素（1 mg/只）和椿乳凝胶低、中、高剂量（0.01、0.02、0.04 g/只）组，另设对照组，每组16只。每天阴道给予相应药物1次，连续20 d，分别于给药第10、20天检测小鼠阴道外观、pH值，末次给药后观察小鼠阴道及宫颈组织病理形态学变化，以及HPV6、HPV11假病毒的病毒滴度，E6、E7基因和蛋白表达，评价椿乳凝胶对低危型HPV病毒的体内抑制作用。结果 体外实验结果显示，椿乳凝胶对HPV6、HPV11假病毒感染能力和所致细胞周期改变具有一定抑制作用。体内实验结果显示，椿乳凝胶能降低HPV6、HPV11假病毒感染能力（P＜0.01），降低小鼠阴道pH值（P＜0.01），减轻宫颈组织病变（P＜0.05、0.01），并且抑制HPV6、HPV11假病毒E6、E7基因和蛋白的表达（P＜0.05、0.01）。结论 HPV6、HPV11假病毒能较好地模拟低危型HPV病毒感染过程，而椿乳凝胶对低危型HPV病毒具有明显的抑制作用，对低危型HPV病毒引起的感染有一定治疗作用。

Objective To study the effect of Chunru Gel (椿乳凝胶) against low risk human papillomavirus (HPV). Methods Low-risk HPV6 and HPV11 pseudovirus-infected human embryonic kidney 293FT cells model was established, and effect of Chunru Gel on HPV infection and cell cycle was evaluated. HPV6 and HPV11 pseudoviruses were injected into vagina of female mice pretreated with estradiol benzoate to establish HPV infected animal models. After virus infection 48 h, virus colonization was detected. The mice models were randomly divided into model group, podophyllotoxin (1 mg/animals) and low-, medium-and high-dose (0.01, 0.02, 0.04 g/animal) Chunru Gel groups, and control group were set up, with 16 animals in each group. The corresponding drugs were administered vaginally once a day for 20 consecutive days. The appearance and pH value of the vagina and cervix of mice were detected on the 10th and 20th day of administration, respectively. After the last administration, the histopathological changes of the vagina and cervix of mice, as well as the viral titer of HPV6 and HPV11 pseudoviruses, and the expression of E6, E7 genes and proteins were observed to evaluate the in vivo inhibitory effect of Chunru Gel on low risk HPV virus. Results The results of in vitro test showed that Chunru Gel had a certain inhibitory effect on infectivity of HPV6 and HPV11 pseudoviruses and cell cycle changes. The results

of in vivo experiments showed that Chunru Gel reduced the infection ability of HPV6 and HPV11 pseudovirus (P < 0.01), reduced the vaginal pH value of mice (P < 0.01), alleviated cervical tissue lesions (P < 0.05, 0.01), and inhibited HPV6, HPV11 pseudovirus E6, E7 gene and protein expressions (P < 0.05, 0.01. Conclusion HPV6 and HPV11 pseudoviruses can better simulate the infection process of low-risk HPV virus, while Chunru Gel has obvious inhibitory effect on low-risk HPV virus, and has a certain therapeutic effect on infection caused by low-risk HPV virus.

R285.5

湖南省重点研发计划项目(2020DK2003)