不同感染方式致豚鼠原发性生殖器疱疹感染情况研究

Primary genital herpes in guinea pigs induced by natural and mucosal damaged infection routes

目的评价自然感染和破损感染两种不同的Ⅱ型单纯疱疹病毒(herpes simplex virus,HSV-2)感染方式建立豚鼠原发性生殖器疱疹模型的效果和疾病特点。方法将78只体质量为300~350 g的雌性豚鼠随机分为空白对照组(n=6)、自然接种DMEM对照组(n=6)、破损接种DMEM对照组(n=6)、自然感染HSV-2组(n=30)和破损感染HSV-2组(n=30)。对自然感染DMEM组、自然感染HSV-2组通过自然感染方式分别向阴道内接种DMEM(0.1 ml)和HSV-2病毒稀释液(剂量为1×105 PFU/只),对破损感染DMEM组、破损感染HSV-2组通过破损感染方式分别向阴道内接种DMEM(0.1 ml)和HSV-2病毒稀释液(剂量为1×105 PFU/只)。感染3 d后采集阴道样本检测HSV-2 DNA拷贝,观察急性感染期内两组豚鼠每天的症状并进行评分量化。通过比较2组豚鼠间的感染率、发病率、病程时长、发病频次以及病变严重程度等指标,对两种病毒感染方式进行比较。结果自然感染和破损感染所致豚鼠的HSV-2感染率分别为96.67%(29/30)、100.00%(30/30),差异无统计学意义(χ^(2)=1.017,P>0.05),但是,同自然感染组比较,破损感染所致豚鼠原发性生殖器疱疹的发病率(96.67%vs 56.67%,χ^(2)=17.865,P<0.01)、病程天数[6(4,8)vs 1(0,3),Z=4.852,P<0.01]、发病频次[2(1,2.25)vs 1(0,2),Z=4.047,P<0.01]和症状严重程度[每日症状平均得分:1.80(1.10,2.15)vs 0.33(0.00,0.87),Z=3.625,P<0.01]均显著增高。结论向豚鼠阴道部位接种HSV-2病毒建立评价HSV-2生殖器疱疹疾病疫苗和治疗性药物效果的动物模型,自然感染方式比破损感染方式更加适用。

Objective To evaluate and compare the effect and disease characteristics of primary genital herpes HSV-2 guinea pig model created through natural infection route and mucosal-damaged infection route.Methods A total of 78 female guinea pigs weighing 300-350 g were divided into 5 groups,including control group(n=6,group 1),naturally inoculated DMEM group(n=6,group 2),DMEM group inoculated through damaged mucosa(n=6,group 3),naturally infected HSV-2 group(n=30,group 4),and HSV-2 group infected through damaged mucosa(n=30,group 5).DMEM(0.1 ml)and HSV-2(1×105 PFU)were inoculated into the guinea pig vaginas,through natural infection and damaged infection,respectively for the naturally infected DMEM group,the naturally infected HSV-2 group,the damaged DMEM group and the damaged HSV-2 group.Vaginal samples were collected 3 days after the infection to determine HSV-2 DNA copies,and the symptoms were recorded and scored daily during the acute infection period.The infection rate,morbidity,duration,frequency and severity of disease were compared between the two HSV-2 groups.Results The infection rates of HSV-2 in guinea pigs in group 4 and group 5 were 96.67%(29/30)and 100.00%(30/30),the difference was not statistically significant(χ^(2)=1.017,P>0.05).However,the incidence rate(96.67%vs 56.67%,χ^(2)=17.865,P<0.01),disease duration[6(4,8)vs 1(0,3),Z=4.852,P<0.01],disease frequency[2(1,2.25)vs 1(0,2),Z=4.047,P<0.01]and disease se⁃verity[average symptom score daily:1.80(1.10,2.15)vs 0.33(0.00,0.87),Z=3.625,P<0.01]in group 5 were significantly higher than those in grop 4.Conclusions Natural infection route is more suitable than mucosadamaged infection route in the creation of an animal model by inoculating HSV-2 virus to the vagina of guinea pigs for evaluating the effect of vaccines and therapeutic drugs of HSV-2 genital herpes disease.