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大鼠因胰岛β细胞自身免疫而导致的严重高血糖症。

Severe hyperglycaemia caused by autoimmunization to beta cells in rats.

作者信息

Ziegler M, Ziegler B, Hehmke B

出版信息

Diabetologia. 1984 Jul;27 Suppl:163-5. doi: 10.1007/BF00275679.

DOI:10.1007/BF00275679
PMID:6237014
Abstract

The non-specific activation of the immune system by administration of complete Freund's adjuvant was examined in Wistar rats as a possible means of amplification of the specific immune response directed to pancreatic B cells caused by low dose non-diabetogenic multiple injections of streptozotocin. Rats were given intraperitoneally 0.5 ml of complete Freund's adjuvant to induce polyclonal lymphocyte activation and, 1 day later, the animals were given an intraperitoneal injection of 15 mg streptozotocin/kg body weight (group 1). This combined treatment was given twice at weekly intervals. In two further groups, rats were treated with complete Freund's adjuvant alone (group 2) or streptozotocin alone (group 3) with the same doses and at the same times. Only the rats in group 1 developed delayed but severe and persistent hyperglycaemia. In addition, significant complement-dependent cytotoxicity was detected in nine out of 15 rats (60%) in group 1 in islet cells, but not in spleen lymphocytes. The pancreatic insulin content of the rats in group 1 was depleted by up to 3.1 +/- 0.5%. With these experiments, a new animal model for insulin-dependent diabetes is described; complete Freund's adjuvant/streptozotocin diabetes. In many aspects, this model of diabetes parallels the development of insulin-dependent diabetes in man, including the humoral autoimmunity to islet cell antigens.

摘要

通过给予完全弗氏佐剂对Wistar大鼠免疫系统进行非特异性激活,以此作为一种可能的手段,来增强由低剂量非致糖尿病性多次注射链脲佐菌素引起的针对胰腺β细胞的特异性免疫反应。给大鼠腹腔注射0.5 ml完全弗氏佐剂以诱导多克隆淋巴细胞激活,1天后,给动物腹腔注射15 mg链脲佐菌素/千克体重(第1组)。这种联合治疗每周进行两次。另外两组大鼠,分别单独用完全弗氏佐剂(第2组)或单独用链脲佐菌素(第3组),剂量和时间相同。只有第1组的大鼠出现了延迟但严重且持续的高血糖症。此外,在第1组的15只大鼠中有9只(60%)的胰岛细胞中检测到显著的补体依赖性细胞毒性,但在脾淋巴细胞中未检测到。第1组大鼠的胰腺胰岛素含量最多减少了3.1±0.5%。通过这些实验,描述了一种新的胰岛素依赖型糖尿病动物模型;完全弗氏佐剂/链脲佐菌素糖尿病。在许多方面,这种糖尿病模型与人类胰岛素依赖型糖尿病的发展相似,包括对胰岛细胞抗原的体液自身免疫。

相似文献

1
Severe hyperglycaemia caused by autoimmunization to beta cells in rats.大鼠因胰岛β细胞自身免疫而导致的严重高血糖症。
Diabetologia. 1984 Jul;27 Suppl:163-5. doi: 10.1007/BF00275679.
2
Autoimmune response directed to pancreatic beta cells in rats induced by combined treatment with low doses of streptozotocin and complete Freund's adjuvant.低剂量链脲佐菌素与完全弗氏佐剂联合处理诱导大鼠胰腺β细胞的自身免疫反应。
Biomed Biochim Acta. 1984;43(5):675-81.
3
Genetic control of diabetes induction by complete Freund's adjuvant combined with subdiabetogenic doses of streptozotocin in Lewis rats--evidence for transient cytotoxicity against beta cells.弗氏完全佐剂联合亚致糖尿病剂量链脲佐菌素诱导Lewis大鼠糖尿病的遗传控制——对β细胞短暂细胞毒性的证据
Exp Clin Endocrinol. 1987 Aug;89(3):269-75. doi: 10.1055/s-0029-1210649.
4
Destruction of pancreatic beta cells in rats by complete Freund's adjuvant combined with non-diabetogenic doses of streptozotocin.用完全弗氏佐剂联合非致糖尿病剂量的链脲佐菌素破坏大鼠胰腺β细胞。
Diabetes Res. 1987 May;5(1):1-11.
5
Survival of islet isografts despite cytotoxicity against pancreatic islets measured in vitro.胰岛同基因移植的存活,尽管在体外检测到对胰岛有细胞毒性作用。
Exp Clin Endocrinol. 1990 Feb;95(1):31-8. doi: 10.1055/s-0029-1210931.
6
Development of cytotoxic islet cell antibodies in rats following damage of the pancreas by complete Freund's adjuvant combined with a nondiabetogenic dose of streptozotocin.用完全弗氏佐剂联合非致糖尿病剂量的链脲佐菌素损伤大鼠胰腺后,大鼠体内细胞毒性胰岛细胞抗体的产生。
Int J Pancreatol. 1990 Jan;6(1):33-48. doi: 10.1007/BF02924342.
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Genetic control of susceptibility to severe hyperglycaemia evoked by CFA/SZ-induced immune response against beta cells in various rat strains.不同大鼠品系中,弗氏完全佐剂/链脲佐菌素诱导的针对β细胞的免疫反应所引发的严重高血糖易感性的遗传控制。
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Synergistic effects of adjuvants, endotoxin, and fasting on induction of diabetes with multiple low doses of streptozocin in rats.佐剂、内毒素和禁食对低剂量链脲佐菌素多次诱导大鼠糖尿病的协同作用。
Diabetes. 1988 Jan;37(1):112-8. doi: 10.2337/diab.37.1.112.
9
Histopathological lesions in the pancreas of a rat model of diabetes induced with complete Freund's adjuvant and low-dose streptozotocin.用完全弗氏佐剂和低剂量链脲佐菌素诱导的糖尿病大鼠模型胰腺中的组织病理学病变
Exp Clin Endocrinol. 1990 Feb;95(1):47-56. doi: 10.1055/s-0029-1210933.
10
Islet beta-cytotoxic monoclonal antibody against glycolipids in experimental diabetes induced by low dose streptozotocin and Freund's adjuvant.针对低剂量链脲佐菌素和弗氏佐剂诱导的实验性糖尿病中糖脂的胰岛β细胞毒性单克隆抗体。
J Immunol. 1988 Jun 15;140(12):4144-50.

引用本文的文献

1
A longitudinal ultrastructural study of pancreatic cellular damage in murine streptozotocin diabetes.小鼠链脲佐菌素糖尿病胰腺细胞损伤的纵向超微结构研究
Acta Diabetol Lat. 1988 Jul-Sep;25(3):185-95. doi: 10.1007/BF02624813.
2
Augmentation of streptozotocin-induced hyperglycemia in mice by prior treatment with complete Freund's adjuvant.
Int J Pancreatol. 1989 Apr;4(3):321-33. doi: 10.1007/BF02938467.
3
Development of cytotoxic islet cell antibodies in rats following damage of the pancreas by complete Freund's adjuvant combined with a nondiabetogenic dose of streptozotocin.用完全弗氏佐剂联合非致糖尿病剂量的链脲佐菌素损伤大鼠胰腺后,大鼠体内细胞毒性胰岛细胞抗体的产生。

本文引用的文献

1
Cellular immune reactions against pancreatic islets as a consequence of graft versus host disease.移植物抗宿主病导致的针对胰岛的细胞免疫反应。
Clin Exp Immunol. 1981 Jan;43(1):121-7.
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Cytotoxic effects of islet cell surface antibodies.胰岛细胞表面抗体的细胞毒性作用。
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3
The diabetogenic effects of streptozotocin in mice are prolonged and inversely related to age.链脲佐菌素对小鼠的致糖尿病作用具有持续性,且与年龄呈负相关。
Int J Pancreatol. 1990 Jan;6(1):33-48. doi: 10.1007/BF02924342.
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Diabetes. 1983 Feb;32(2):148-55. doi: 10.2337/diab.32.2.148.
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Diabetes. 1982 Sep;31(9):808-15. doi: 10.2337/diab.31.9.808.
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Islet-cell-surface antibodies in juvenile diabetes mellitus.
N Engl J Med. 1978 Aug 24;299(8):375-80. doi: 10.1056/NEJM197808242990802.
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