SARS-CoV的S蛋白引起小鼠急性肺损伤  

Acute lung injury in mice caused by SARS-CoV spike glycoprotein

作　　者：杨新艳[1] 要国华[1] 徐军[1] 钟南山[1] 

机构地区：[1]广州医学院第一附属医院,广州呼吸疾病研究所,广东广州510120

出　　处：《中国病理生理杂志》2009年第5期980-983,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30340029);广东省教育厅非典专项经费资助项目

摘　　要：目的:研究严重急性呼吸综合征冠状病毒(SARS-CoV)的S蛋白作用于小鼠发生的免疫和病理变化,试图揭示S蛋白引起急性肺损伤的可能机制。方法:将BALB/c小鼠随机分为PBS空白对照组、S蛋白组和γ-干扰素可诱导的10kD蛋白(IP-10)组,分别经气管滴注、尾静脉注射的途径注入,观察其临床症状、死亡率;称取双肺湿重,进行HE染色和免疫荧光方法检测肺组织中IP-10的表达。结果:经气管滴注或尾静脉注射S蛋白均可导致小鼠出现呼吸急促症状,甚至死亡,肺脏湿重增加,显微镜下可见肺泡正常结构破坏,间质增厚,炎性细胞浸润,上皮细胞和血管内皮细胞的肿胀脱落,小鼠肺内气管上皮细胞和血管内皮细胞均强阳性表达IP-10。经气管滴注小鼠IP-10蛋白小鼠出现上述类似的肺损伤表现。结论:(1)SARS-CoV的S蛋白引起小鼠急性肺损伤。(2)SARS-CoV的S蛋白可诱导小鼠肺组织表达IP-10。(3)经气管滴注小鼠IP-10可引起小鼠肺损伤。AIM ： To investigate the effect of spike protein of SARS - CoY on the pathological and immunological changes in the lungs of mice and to explore the mechanism of spike protein induced acute lung injury. METHODS： BALB/c mice were randomly divided into groups： control （PBS）, spike protein and γ- interferon- inducible protein- 10 （IP- 10）. The agents were given either by intracheal instillation or tail venous injection. Clinical symptom and mortality were observed. Whole wet lungs were separated and weighed, then fixed in formalin, embedded in paraffin, section slices were stained with hematoxylin and eosin for pathological examination. Expression of IP - 10 in the lung of mice was evaluated using immunofluorescence method. RESULTS： Mice received spike protein inhalation or injection appeared to be short of breath, and died. Increased lung wet weight, obvious alveolar destruction, mesenchyma infiltration with inflammatory cells, epithelial and vascular endothelial swelling and shedding were demonstrated in spike protein group. Similar lung injury was found in the IP - 10 group. Spike protein induced the expression of IP - 10 in the airway epithelium and vascular endothelium of the lung. CONCLUSION： （ 1 ） Spike protein of SARS - CoV administered by inhalation or injection causes acute lung injury in mice. （2） Spike protein of SARS - CoV induces the expression of IP - 10 in the lung of mice. （3） IP - 10 causes acute lung injury in mice.

关 键 词：严重急性呼吸综合征 冠状病毒属 Spike糖蛋白 γ干扰素诱导蛋白10 

分 类 号：R16[医药卫生—公共卫生与预防医学]