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前列腺素E1对NZB/NZW F1杂交小鼠的治疗。II. 肾小球肾炎的预防

Prostaglandin E1 treatment of NZB/NZW F1 hybrid mice. II. Prevention of glomerulonephritis.

作者信息

Zurier R B, Damjanov I, Sayadoff D M, Rothfield N F

出版信息

Arthritis Rheum. 1977 Nov-Dec;20(8):1449-56. doi: 10.1002/art.1780200802.

Abstract

The F1 hybrid of New Zealand black and New Zealand white mice--the NZB/NZW mouse--spontaneously develops a disease similar to human systemic lupus erythematous, characterized by impaired cell-mediated and enhanced humoral immune responses, development of antibodies to nuclear antigens, and immune complex glomerulonephritis. Because there is experimental evidence that prostaglandin E1 (PGE1) can enhance T-cell function and cell-mediated responses and suppress B-cell activity, NZB/NZW mice were treated with 200 microgram PGE1 subcutaneously once or twice daily from 6 weeks of age. PGE1 treatment of female and male mice prevents giomerular deposition of immunoglobulins and complement (monitored by immunofluorescence), and development of the proliferative glomerulonephritis (determined by light and electron microscopy) characteristic of untreated NZB/NZW mice. After 1 year of treatment, 18 of 19 female mice survived, whereas only 2 of 19 untreated control mice were alive. Male mice treated with 200 microgram PGE1 daily were also protected: 9 of 11 versus 2 of 9 untreated mice were alive at 65 weeks. PGE1 treatment did not prevent development of antibodies to nuclear material in any of the treated groups.

摘要

新西兰黑鼠和新西兰白鼠的杂交一代——NZB/NZW小鼠——会自发患上一种类似于人类系统性红斑狼疮的疾病,其特征为细胞介导免疫反应受损、体液免疫反应增强、出现针对核抗原的抗体以及免疫复合物性肾小球肾炎。由于有实验证据表明前列腺素E1(PGE1)可增强T细胞功能和细胞介导反应,并抑制B细胞活性,因此从6周龄开始,对NZB/NZW小鼠每日皮下注射200微克PGE1,注射一次或两次。PGE1治疗雌鼠和雄鼠可防止免疫球蛋白和补体在肾小球沉积(通过免疫荧光监测),并防止出现未治疗的NZB/NZW小鼠所特有的增殖性肾小球肾炎(通过光学显微镜和电子显微镜确定)。治疗1年后,19只雌鼠中有18只存活,而19只未治疗的对照小鼠中只有2只存活。每日接受200微克PGE1治疗的雄鼠也受到了保护:在65周时,11只接受治疗的雄鼠中有9只存活,而9只未治疗的雄鼠中只有2只存活。PGE1治疗并未阻止任何一个治疗组中针对核物质的抗体的产生。

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