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目的通过动态监测小鼠严重急性呼吸综合征(SARS)样模型肝脏的组织病理学变化和病毒分布情况,进一步结合肝内凝血酶原酶(fg12)的表达和纤维素沉积现象来探讨SARS肝脏损伤的可能机制及其临床意义。方法实验组Ba1b/cJ近交系小鼠气管途径感染100 PFU鼠肝炎3型病毒(MHV-3),平行设立0．9%氯化钠溶液对照组,动态观察感染后两组小鼠的一般情况、组织脏器的病理学改变和肝功能损伤情况。标准噬斑法和原位杂交技术检测实验组小鼠组织器官的病毒分布情况。结合感染后肝组织中纤维素的表达,分别从蛋白和基因转录水平探讨fg12作为一种促炎症因子在SARS肝损伤中的作用。结果实验组小鼠5 d内死亡率高达100%,组织病理学观察发现病变可累及多个脏器,其中肝脏小叶结构基本完整,肝细胞弥漫混浊肿胀,大面积气球样变和水样变,汇管区少量淋巴细胞浸润,偶见中央静脉周围肝细胞的点灶状坏死；肺脏呈现典型间质性肺炎样改变伴透明膜、微小血栓形成；非特异性炎性改变亦见于脾脏、肾脏等其他脏器。噬斑试验和原位杂交显示病毒可侵犯所有收集的组织脏器。随着感染时间的延长,小鼠肝脏功能受损,fg12(mfg12)转录和表达可出现在感染肝脏的坏死区域,周围伴有纤维素沉积。对照组小鼠全部健康存活。结论利用MHV-3成功建立了小鼠SARS样模型,并提示其肝脏损伤在病理学改变和病变程度上均类似于人类SARS合并的非特异性肝炎,除病毒本身所致的肝细胞病变,mfg12在感染后肝组织中的特异性表达及其诱导的纤维素沉积可能是造成肝脏损伤的又一重要因素。
Objective To investigate the histopathological changes and virus distribution in the liver of mice with severe acute respiratory syndrome (SARS) -like model and further investigate the expression of fibrinogen (fg12) Possible mechanism and clinical significance. Methods The mouse model of Ba1b / cJ inbred mice was infected with 100 PFU murine hepatitis 3 virus (MHV-3) in the trachea, and 0.9% sodium chloride solution control group was established in parallel. The dynamic changes of the mice in the two groups were observed Condition, histopathological changes of organs and damage of liver function. Standard plaque method and in situ hybridization technique were used to detect the virus distribution in the tissues and organs of experimental mice. Combined with the expression of cellulose in infected liver tissue, we investigated the role of fg12 as a proinflammatory cytokine in the pathogenesis of SARS-induced liver injury. Results The death rate of mice in experiment group was as high as 100% within 5 days. Histopathological observation showed that the pathological changes could involve multiple organs. The structure of liver lobes was basically intact, the hepatocytes were diffusely cloudy and swollen, large-area balloon- A small amount of lymphocyte infiltration in the portal area, occasionally focal necrosis of the liver cells around the central vein; the lung showed typical interstitial pneumonia-like changes with the transparent membrane, small thrombosis; non-specific inflammatory changes are also found in spleen, kidney and other dirty Device. Plaque testing and in situ hybridization showed that the virus could invade all the collected tissue organs. With prolonged infection, mice have impaired liver function, and transcription and expression of fg12 (mfg12) can occur in necrotic areas of the liver infected with deposition of cellulose. Control mice all survived. Conclusions The murine SARS-like model was successfully established by using MHV-3, and its liver injury was similar to non-specific hepatitis with SARS in pathological changes and pathological changes. Apart from the hepatocytopathic effect caused by the virus itself, mfg12 Specific expression in hepatic tissue after infection and its induced deposition of cellulose may be another important factor in causing liver damage.