Basic study on prevention and treatment of type 1 diabetes mellitus with biological respomse modifiers.

生物反应调节剂防治1型糖尿病的基础研究。

• 批准号: 61570536
• 负责人: SATOH Jo
• 金额: $ 1.34万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570536/
• 关键词: type 1 diabetes mellitus; IDDM; BRMs; OK-432; NOD mouse; BB rat; 糖尿病の免疫療法; 【I】型糖尿病; インスリン依存型糖尿病; 免疫修飾剤

We previously reported that a streptococcal preparation (OK-432), one of BRMs, inhibited insulitis and prevented insulin-dependent (type 1) diabetes mellitus (IDDM) in NOD mice. In this project, we extended our previous observation to two studies; 1) effect of OK-432 on IDDM in BB rats as an another model of IDDM and 2) analysis of mechanisms of OK-432-action by usingNOD mice. The results and conslusions are as follows.1)The cumulative incidence of diabetes was 27.7% (13/47) by 30 weeks of age in BB rats, whereas that was significantly suppressed in the rats (7.4%, 4/54, p<0.01) who were weekly and intraperitoneally treated with 0.2 mg of OK-432. Histological examinations revealed that the OK-432-treated BB rats retained a greater number of intact islets without lymphocytic infiltrations than did thenon-treated rats. The cytotoxic activities of spleen cells directed against a rat insulinoma cell line, RIN, were significantly suppressed in the OK-432-treated BB rats as compared with tho … More se in the non-treated rats, Thus, the OK-432 treatment suppressed insulitis and inhibited development of diabetes not only in NOD mice but also in BB rats.2) Approximately 85% of the non-treated NOD mice developed diabetes by 25 weeks of age. On the other hand, the weekly injection (ip or iv) of 0.1mg of OK-432 from 4 or 5 to 15 ro 20 weeks of age completely inhibited development of diabetes and these NOD mice did not develop diabetes even after ceasing the OK-432-treatment. Cyclophosphamide enhanced the development of diabetes in thenon-treated NOD mice but not in the OK-432-treated mice. The diabetes wastransfered by the spleen cells from the non-treated NOD mice but not by the cells from the OK-432-treated mice. In addition, the spleen cells from the OK-432-treated mice inhibited the development of diabetes in the cyclophosphamide-treated mice and this inhibitory effect was eliminated by the treatment of cells with anti-Thy-1 antibody and complement. These indicate that the OK-432-treatment inhibited the induction of cytotoxic effector cells directed against pancreatic B cells and this effect was mediated by suppressor T cells. Less

我们之前曾报道过一种链球菌制剂(OK-432)，它是BRM之一，可以抑制NOD小鼠的胰岛素依赖型(1型)糖尿病(IDDM)并抑制胰岛素炎症。在本项目中，我们将先前的观察扩展到两个研究：1)OK-432对作为另一种IDDM模型的BB大鼠的作用；2)用NOD小鼠分析OK-432的作用机制。结果和结论如下：1)30周龄BB大鼠糖尿病累积发病率为27.7%(13/47)，而每周口服0.2 mg OK-432的大鼠糖尿病累积发病率为7.4%(4/54，p&lt；0.01)。组织学检查显示，OK-432处理的BB大鼠保留的完整胰岛数量比未处理的大鼠更多，没有淋巴细胞渗透。与…相比，OK-432处理的BB大鼠的脾细胞对大鼠胰岛素瘤细胞系RIN的细胞毒活性显著受到抑制因此，OK-432治疗不仅抑制了NOD小鼠和BB大鼠的胰岛素炎和糖尿病的发展，而且抑制了糖尿病的发展。2)大约85%的未治疗NOD小鼠在25周龄时患上了糖尿病。另一方面，从4周龄或5周龄到15周龄或20周龄每周注射0.1 mg OK-432完全抑制了糖尿病的发展，这些NOD小鼠即使在停止使用OK-432治疗后也没有发生糖尿病。环磷酰胺可促进NOD组小鼠糖尿病的发生，但对OK-432组小鼠无明显影响。糖尿病通过未治疗的NOD小鼠的脾细胞转移，而不是通过OK-432治疗的小鼠的细胞转移。此外，OK-432处理的小鼠的脾细胞抑制环磷酰胺处理的小鼠糖尿病的发展，这种抑制作用可被抗Thy-1抗体和补体处理的细胞所消除。提示OK-432处理可抑制针对胰腺B细胞的细胞毒效应细胞的诱导，这种作用是由抑制性T细胞介导的。较少

项目成果

新谷茂樹,他: 糖尿病動物. (1987)

Shigeki Shintani 等人：糖尿病动物（1987）。

Jo Satoh et al: "NOD/Sendai mice with high incidence of type 1 diabetes are not T lymphocytopenic" in submission.

Jo Satoh 等人提交的文章中称：“1 型糖尿病发病率高的 NOD/Sendai 小鼠并非 T 淋巴细胞减少症”。

佐藤譲,他: 日本内科学会雑誌. 76. 124 (1987)

Yuzuru Sato 等人：日本内科学会杂志 76. 124 (1987)。

後藤由夫,佐藤譲他編: "糖尿病動物1・OK-432によるBBラット糖尿病発症の抑制" 医療ジャーナル社, 101-107 (1987)

Yoshio Goto、Yuzuru Sato 等编：“糖尿病动物 1 和 OK-432 对 BB 大鼠糖尿病发病的抑制”医学杂志出版，101-107 (1987)

新谷茂樹,他: 日本免疫学会総会・学術集会記録. 16. 678 (1986)

Shigeki Shintani 等：日本免疫学会会员大会和学术会议记录 16. 678 (1986)。