A study of pathogenesis of viral hepatitis by quantitative analysis

分别以接种小鼠肝炎病毒的ICR小鼠、接种MHV-2S、MHV-2 M、MHV-2L的裸鼠和接种MHV-2cc的裸鼠作为急性和慢性病毒性肝炎的模型，首先在前一实验系统中进行检查，主要是在胸腺、淋巴结和脾脏等淋巴器官中，使用图像分析系统（皮亚斯III）进行检查。随着Thy-1阳性细胞的减少，病变加重，表明淋巴器官的损害是肝炎加重的原因之一，肝内病毒抗原在部分肝细胞和枯否细胞中形成，并广泛扩散到大部分肝细胞。在使用弱毒力突变体（MHV-2S和-2M）的实验中，发现早期形成小的局灶性病变，然后变得更加严重。在使用无胸腺小鼠和MHV弱毒力突变体系统的慢性肝炎中，接种毒力最低的MHV-2L的小鼠出现病变逐渐扩大，形成慢性浸润性肝炎。结果表明，其它突变株的病毒滴度均迅速升高，不适于制作慢性肝炎模型，图像分析仪计算肝损伤面积随肝损伤程度的不同而变化，说明图像分析仪在评价肝损伤中的作用。采用无胸腺小鼠和MHV-2cc系统。在一组从病毒接种开始就给予干扰素的小鼠中，病毒滴度、肝酶值和肝损害面积之间存在良好的相关性，表明图像分析系统可以定量评价慢性肝炎的损害程度。

ICR mice inoculated with mouse hepatitis virus, MHV-2S, -2M, -2L and athymic nude mice inoculated with MHV-2cc were used as models of acute and chronic viral hepatitis, respectivelyAt first, the examination was carried out in the former experimental system, mainly in lymphatic organs such as the thymus, lymph nodes and spleen, using an image analyzer system (PIAS III). The lesions became severer in accordance with the decrease of Thy-1 positive cells and it was demonstrated that the damage of the lymphoid organs was one of the causes that made hepatitis severer.Viral antigen in the liver was formed in both some hepatocytes and Kupffer cells and widely spread to most of hepatocytes. In an experiment using low virulent mutants (MHV-2S and -2M) revealed that small focal lesions were formed in the early stage, then became severer.In the chronic hepatitis using the system athymic mice and low virulent mutants of MHV, mice inoculated with MHV-2L, the lowest virulence, showed gradual enlargement of lesions and made chronic infiltrating hepatitis. By inoculation of the other mutants, viral titer increased rapidly showing those were unsuitable for making the model of chronic hepatitis.Increase of areas of hepatic lesions by calculation with the image analyzer changed with the severity of hepatic lesions those showed the utility of the image analyzer for evaluation of the hepatic lesions.To evaluate the effects of interferon in chronic hepatitis, the system of athymic mice and MHV-2cc was used. In a group of mice seriously administered with interferon from the time of viral inoculation, viral titer, the value of hepatic enzyme and areas of hepatic lesion were well corelated, those demonstrated that the image analyzer system made possible to evaluate the lesion of chronic hepatitis quantitatively.