1型单纯疱疹病毒经不同途径感染小鼠建立病理模型的比较分析

Comparative analysis of establishment of pathological model by infection of mice with herpes simplex virus type 1 by different routes

目的比较分析1型单纯疱疹病毒(herpes simplex virus type 1,HSV-1)经不同途径感染小鼠所建立的病理模型。方法将成年鼠分别经眼角膜、牙龈、鼻黏膜、皮下及尾静脉感染HSV-1,50μl/只,临床观察60 d,感染后第3和6天,取脑组织及脊髓,进行组织病理学观察,并检测病毒载量。将乳鼠经脑内和后肢注射感染HSV-1,10~7 CCID_(50)/(ml·g),临床观察2周,感染后第3天,取脑及后肢肌肉组织,进行组织病理学观察,并检测病毒载量。结果鼻黏膜组成年鼠感染20 d后,面部皮肤溃烂,眼角膜组感染47 d后,眼部出现红肿、充血;除尾静脉组和牙龈组外,其他组小鼠体重均呈升高趋势;未出现死亡情况。各组成年鼠脑组织和脊髓中均出现出血及炎性细胞浸润,感染后第3天脑中病毒载量最高。1、3、7日龄乳鼠经脑及后肢注射后均出现后肢麻痹症状,经脑部注射后死亡率分别为100%、100%和91.7%,经后肢注射后死亡率分别为90.9%、78.5%和72.7%。病毒感染后第3天,各组乳鼠均出现脑出血、血管袖套及少量炎性细胞浸润,个别乳鼠脑部见针迹灶;后腿肌肉仅见少量炎性细胞浸润现象,大脑和后腿肌肉组织中的病毒滴度为3.5~4.5 1og10CCID50/100 mg。结论乳鼠对HSV-1普遍易感,且病理损伤与成年鼠相似,本研究建立的乳鼠模型可用于疫苗株或减毒株的筛选和评价,为HSV-1疫苗的研发奠定了基础。

Objective To compare the pathological model established by infection of mice with simplex virus type 1（HSV-1）by different routes. Methods Adult mice were infected with HSV-1 by ocular, gingival, nasal mucosa, subcutaneous and intravenous routes respectively, 50 μl for each, and observed for 60 d, of which the brain tissue and spinal cord were collected on days 3 and 6 after infection for histopathological examination and determination of virus load.Suckling mice were infected with HSV-1 at a dosage of 107CCID50/（ml · g） by intracerebral and intramuscular routes respectively, and observed for 2 weeks, of which the brain and muscle tissues were collected on days 3 after infection for histopathological examination and determination of virus load. Results The skin on face of adult mice festered 20 d after infection through nasal mucosa, while redness, swelling and hyperemia of eyes were observed in mice 47 d after infection by ocular route. Except those infected by intravenous and gingival routes, the bodyweights of mice in other groups showed increasing tendencies. No deaths of mice appeared. Bloody and inflammatory cellular infiltrations were observed in brain and spinal cord tissues of adult mice in various groups, while the virus load in brain on day 3 after infection was the highest. Limb paralyses were observed in suckling mice at ages of 1, 3 and 7 days after infection by intracerebral and intramuscular routes, while the mortality rates were 100%, 100% and 91. 7% after intracerebral infection, and 90. 9%,78. 5% and 72. 7% after intramuscular infection, respectively. Cerebral hemorrhage, vascular cuff and a small quantity of inflam-matory cellular infiltration were observed in sucklin g mice of various groups on day 3 after virus infection, while needle foci in brain of individual suckling mice. Only a small quantity of inflammatory cellular infiltration was observed in the muscle of behind limbs. The virus titers in brain and muscle of behind limbs were 3. 5 ~ 4. 5 log10CCID50/100 mg.Conclusion Suckling was susceptible to HSV-1, of which the pathological lesion was similar to that of adult mice. The established suckling mouse model might be used for the screening and evaluation of vaccine strain or attenuated strain,which laid a foundation of development of HSV-1 vaccine.