Immuno-pathological studies in IgA nephropathy : The role of virus for etiological and progressive factors

为了建立IgA肾病的实验模型，对接种病毒的小鼠进行了组织学和病毒学研究。首先，小鼠静脉接种两次，间隔1-28天，用Cox纯化。B4病毒。每只小鼠在第二次接种36小时后取肾，检查肾系膜沉积等组织学变化。在间隔14天或更长时间接种两次的小鼠中，系膜沉积被标记出来，表明在足够长的间隔内重复的抗原刺激对于产生系膜沉积是必要的。另一组4周龄小鼠接种Cox。B4病毒每隔4周静脉注射（静脉注射组）或腹腔注射（腹腔注射组）4-8次。最后一次接种一个月后，取每只小鼠的肾脏，检查组织学变化。在静脉注射组，光镜检查显示，接种4次后系膜内PAS阳性沉积。接种6次以上后，沉积更为明显，并伴有环壁不均匀肥大和月牙形成。免疫荧光法观察，接种4、5次后获得的样品中IgG染色最深，而接种6次及以上获得的部分样品中IgA和IgG染色程度相同。所有标本均呈病毒ag阳性，染色强度随接种次数成比例增加。电镜显示在上皮下和内皮下军团有沉积物。在i.p.组，光镜显示4次或更多接种后系膜pas阳性沉积。接种6次以上后，基底膜不均匀肥大，但未形成月牙。免疫荧光法检测系膜中IgG、IgA、IgM深度染色；IgA总是以染色为主。病毒抗原在所有标本中均呈阳性。电镜观察结果与静脉注射组相似。因此，证明间歇性腹腔注射Cox。B4病毒在小鼠体内产生的肾脏病变与人类IgA肾病非常相似。少

In order to produce an experimental model of IgA nephropathy, a histologiral and virological study of mice inoculated with a virus was carried out. First, mice were intravenously inoculated twice at an interval of 1-28 days purified with Cox.B4 virus. The kidneys were obtained from each mouse 36 hours after the second inoculation, and examined for histological changes such as mesangial deposits. Mesangial deposits were marked in mice given two inoculation at an interval of 14 days or more, indicating that antigen stimulations repeated at a sufficiently long interval are necessary for producing mesangial deposits. Another series of 4-week-old mice were inoculated with Cox.B4 virus 4-8 times at 4-week intervals either intravenously (i.v. group) or intraperitoneally (i.p. group). The kidneys were obtained from each mice one month after the final inoculation, and examined for histological changes. In the i.v. group, light microscopy revealed PAS- positive deposits in the mesangium after 4 … More inoculations. The deposits were more marked after 6 or more inoculations, accompanied by uneven hypertrophy of the loop wall and formation of crescents. By immunofluorescence, IgG was most deeply stained in speciments obtained after 4 or 5 inoculations, whereas IgA and IgG were stained to the same degree in some speciments after 6 or more inoculations. All speciments were positive for virus-Ag, the intensity of staining being increased in proportion to the number of inoculations. Electron microscopy disclosed deposits in subepithelial and subendothelial legions. In the i.p. group, light microscopy showed PAS-positive deposits in the mesangium after 4 or more inoculations. After 6 or more inoculations, there was uneven hypertrophy of the basement membrane, but no formation of crescents. By immunofluorescence, IgG, IgA and IgM were deeply stained in the mesangium in comparison with controls; IgA was always stained predominantly. Virus-Ag was positive in all speciments. Electron microscopic findings were similar to those in the i.v. group. It was thus demonstrated that intermittent intraperitoneal inoculation with Cox.B4 virus in mice produces renal lesions closely resembling those in human IgA nephropathy. Less