中、重症呼吸道合胞病毒感染小鼠模型的实验研究

Experimental Study on Mouse Model of Moderate and Severe Respiratory Syncytial Virus Infection

目的建立呼吸道合胞病毒（RSV）感染的中、重症小鼠模型。方法36只小鼠分为实验Ⅰ组（16只）、实验Ⅱ组（16只）和正常对照组（4只）。采用RSV原液（TCID50为10^4.2／100μl及100TCID50RSV液分别滴鼻感染实验Ⅰ、Ⅱ组BALB／c小鼠，于感染后第3、5、7、9d处死小鼠，进行病毒分离，病理光镜和电镜检查。结果①实验Ⅰ组的病毒分离阳性率明显高于实验Ⅱ组，二者相比有显著性差异（P〈0．01）；②光镜下实验I组肺泡壁明显增厚，毛细血管扩张充血，有较多的淋巴细胞浸润，以Ⅲ级炎症为主；实验Ⅱ组病变较实验Ⅰ组轻，Ⅲ级炎症面积及炎性细胞浸润支气管百分数少于实验Ⅰ组，两组间有显著差异（P〈0．05）。2组病变以第5d最重，第7d后开始减轻。⑧电镜下实验Ⅰ组可见肺泡Ⅰ型、Ⅱ型上皮细胞及毛细血管内皮细胞肿胀，肺泡隔水肿，淋巴细胞、单核细胞和嗜酸性粒细胞浸润；实验Ⅱ组病变轻于实验Ⅰ组。结论用RSV原液可以成功地建立中、重症RSV感染的动物模型。

Objective To establish the mouse model of moderate and severe respiratory syncytial vires infection. Methods BALB/c mouse were infected by RSV stock solution （TCID50, 10 -4. 2/ 100μl） and 100TCID50RSV dropping in nasal cavity. On 3, 5, 7 and 9 days post infection, the mouse were killed, then viral isolation, light and electron microscope examination were performed respectively. Results The positive rate of viral isolation in the RSV stock solution group （ experimental group Ⅰ） was obviously higher than that in the 100TCID50RSV group （experimental group Ⅱ） with significant statistics difference between them （P 〈 0. 01 ）. Under light microscope, alveolar wall thickened significantly and capillary engorged with more lymphocytic infiltration in experimental group Ⅰ, and the third grade inflammation was dominating. While in experimental group Ⅱ, response was more palliative than that in experimental group Ⅰ. And the area of the third grade inflammation and the percentage of inflammatory cell infiltrate bronchus were less than in experimental group Ⅰwith significant statistics difference （P 〈 0. 05 ）. Affection was the most serious in the fifth day and it began to relieve after the seventh day. Under electron microscope, type Ⅰ, Ⅱ alveolar epithelial cell and capillary endothelium cell were swelling, interalveolar septum was edema and lymphocytic, monocyte and eosinophile granulocyte infiltration were seen in experimental group Ⅰ. Affection in experimental group Ⅱ was more palliative than that in experimental group Ⅰ. Conclusion Mouse model of moderate and severe RS virus infection can be constructed successfully by RSV stock solution.