Prevention of Autoimmune Diabetes in NOD Mice by Dimethyl Fumarate.
Prevention of Autoimmune Diabetes in NOD Mice by Dimethyl Fumarate.
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DOI：
10.3390/antiox10020193
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发表时间：
2021-01-29
期刊：
影响因子：
--
通讯作者：
Ichii H
中科院分区：
文献类型：
--
作者：
Li S;Vaziri ND;Swentek L;Takasu C;Vo K;Stamos MJ;Ricordi C;Ichii H
氧化应激在糖尿病的发病机制中起着关键作用。这项研究测试了这样的假设：通过保护 β 细胞免受氧化应激和炎症的影响，Nrf2 激活剂富马酸二甲酯 (DMF) 可以预防或延缓非肥胖糖尿病 (NOD) 小鼠 1 型糖尿病的发病。首先，进行胰岛分离以确认口服DMF对胰岛细胞的抗氧化作用。其次，在自发性糖尿病模型中，从 8 周龄开始直至 22 周龄，每天给小鼠喂食一次 DMF（25 mg/kg）。在环磷酰胺诱导的加速糖尿病模型中，给小鼠喂食 DMF（25 毫克/千克），每天两次，持续两周。在胰岛分离研究中，DMF 施用提高了胰岛中的分离率、减弱了氧化应激并增强了 GCLC 和 NQO1 表达。在自发模型中，与对照组相比，DMF 显着降低了糖尿病的发病率（25% vs. 54.2%）。在加速模型中，DMF 将糖尿病发病率从 58.3% 降低至 16.7%。 DMF治疗组胰岛的胰岛炎评分（1.6±0.32）显着低于对照组（3.47±0.21）。 DMF治疗组血清IL-1α、IL-1β、IL-2、IL-4、IL-5、IL-6、IL-9、IL-12p70、IFN-γ、TNF-α、MCP-1、CXCL16的含量低于对照组。总之，DMF 可以通过减弱胰岛炎和促炎细胞因子的产生来保护 NOD 小鼠的胰岛细胞并降低自身免疫性糖尿病的发生率。
Oxidative stress plays critical roles in the pathogenesis of diabetes. This study tested the hypothesis that by protecting β-cells against oxidative stress and inflammation, an Nrf2 activator, dimethyl fumarate (DMF), may prevent or delay the onset of type 1 diabetes in non-obese diabetic (NOD) mice. Firstly, islet isolation was conducted to confirm the antioxidative effects of DMF oral administration on islet cells. Secondly, in a spontaneous diabetes model, DMF (25 mg/kg) was fed to mice once daily starting at the age of 8 weeks up to the age of 22 weeks. In a cyclophosphamide-induced accelerated diabetes model, DMF (25 mg/kg) was fed to mice twice daily for 2 weeks. In the islet isolation study, DMF administration improved the isolation yield, attenuated oxidative stress and enhanced GCLC and NQO1 expression in the islets. In the spontaneous model, DMF significantly reduced the onset of diabetes compared to the control group (25% vs. 54.2%). In the accelerated model, DMF reduced the onset of diabetes from 58.3% to 16.7%. The insulitis score in the islets of the DMF treatment group (1.6 ± 0.32) was significantly lower than in the control group (3.47 ± 0.21). The serum IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-12p70, IFN-γ, TNF-α, MCP-1 and CXCL16 levels in the DMF-treated group were lower than in the control group. In conclusion, DMF may protect islet cells and reduce the incidence of autoimmune diabetes in NOD mice by attenuating insulitis and proinflammatory cytokine production.
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