Inhibition of NLRP3 Inflammasome Ameliorates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice.
Inhibition of NLRP3 Inflammasome Ameliorates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice.
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抑制 NLRP3 炎症小体可改善糖尿病小鼠脑缺血再灌注损伤
DOI：
10.1155/2018/9163521
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发表时间：
2018
影响因子：
3.1
通讯作者：
Zhang HF
中科院分区：
文献类型：
--
作者：
Hong P;Li FX;Gu RN;Fang YY;Lai LY;Wang YW;Tao T;Xu SY;You ZJ;Zhang HF
NLRP3炎症小体的持续激活与糖尿病和中风密切相关。然而，NLRP3 炎性体是否在糖尿病中风中发挥重要作用尚不清楚。我们的目的是探讨NLRP3炎性小体对糖尿病小鼠脑缺血再灌注损伤的作用及其潜在机制。通过高脂饮食和链脲佐菌素 (STZ) 诱导 2 型糖尿病小鼠模型。糖尿病小鼠在大脑中动脉闭塞 (MCAO) 和再灌注前 60 分钟接受 MCC950（特定分子 NLRP3 抑制剂）或载体治疗。 MCC950降低了糖尿病小鼠脑缺血再灌注后24小时的神经功能缺损评分，提高了脑缺血再灌注损伤的28天生存率。此外，我们发现在脑缺血再灌注损伤的糖尿病小鼠中，核心缺血区的NLRP3、IL-1β和caspase-1的mRNA转录水平显着增强，而MCC950预处理明显减弱了这种现象。总之，NLRP3炎性体参与了糖尿病脑卒中的复杂疾病。 NLRP3特异性抑制剂MCC950可改善糖尿病小鼠的脑缺血再灌注损伤，并提高缺血性中风恢复期的28天生存率。
Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1β, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.
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影响因子：
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作者：
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DOI：
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期刊：
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