Neuroprotective effect of Notch pathway inhibitor DAPT against focal cerebral ischemia/reperfusion 3 hours before model establishment
Neuroprotective effect of Notch pathway inhibitor DAPT against focal cerebral ischemia/reperfusion 3 hours before model establishment
复制标题
Notch通路抑制剂DAPT对模型建立前3小时局灶性脑缺血/再灌注的神经保护作用
DOI：
10.4103/1673-5374.245469
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Yan Yu
中科院分区：
文献类型：
--
作者：
Jun-Jie Wang;Jun-De Zhu;Xian-Hu Zhang;Ting-Ting Long;Guo Ge;Yan Yu
N-[N-(3,5-二氟henacetyl)-l-alanyl]- s -phenylglycine叔丁基酯（DAPT）作为Notch信号通路的抑制剂，对脑组织严重缺血损伤具有保护作用。本研究旨在探讨DAPT在脑缺血再灌注（I/R）损伤后的神经保护作用。DAPT于梗阻小鼠大脑右中动脉局灶性脑I/R模型建立前3小时腹腔注射。使用Longa评分来评估小鼠的神经变化。Nissl染色和tdt介导的dutp -生物素镍端标记染色检测右侧前额叶皮层神经元损伤和细胞凋亡，免疫荧光染色检测胶质纤维酸性蛋白和notch1阳性细胞。western blot法检测右侧前额皮质Hes1、Hes5蛋白表达水平。我们的研究结果表明，DAPT可以显著改善神经行为评分，减轻神经元形态学损伤。DAPT降低右侧前额叶皮层胶质原纤维酸性蛋白和notch1阳性细胞数量，减少凋亡细胞数量，降低白细胞介素-6和肿瘤坏死因子-α含量，同时下调Hes1和Hes5蛋白表达。这些结果验证了DAPT可以减轻脑I/R损伤后的病理病变，增强抗炎反应。因此，DAPT有望成为预防脑I/R损伤的有效药物。
As an inhibitor of the Notch signaling pathway, N-[N-(3,5-difluorohenacetyl)-l-alanyl]-S-phenylglycine tert-butyl ester (DAPT) may protect brain tissue from serious ischemic injury. This study aimed to explore neuroprotection by DAPT after cerebral ischemia/reperfusion (I/R) injury. DAPT was intraperitoneally injected 3 hours before the establishment of a focal cerebral I/R model in the right middle cerebral artery of obstructed mice. Longa scores were used to assess neurological changes of mice. Nissl staining and TdT-mediated dUTP-biotin nick-end labeling staining were used to examine neuronal damage and cell apoptosis in the right prefrontal cortex, while immunofluorescence staining was used to detect glial fibrillary acidic protein- and Notch1-positive cells. Protein expression levels of Hes1 and Hes5 were detected by western blot assay in the right prefrontal cortex. Our results demonstrated that DAPT significantly improved neurobehavioral scores and relieved neuronal morphological damage. DAPT decreased the number of glial fibrillary acidic protein- and Notch1-positive cells in the right prefrontal cortex, while also reducing the number of apoptotic cells and decreasing interleukin-6 and tumor necrosis factor-α contents, and simultaneously downregulating Hes1 and Hes5 protein expression. These findings verify that DAPT alleviates pathological lesions and strengthens the anti-inflammatory response after cerebral I/R injury. Thus, DAPT might be developed as an effective drug for the prevention of cerebral I/R injury.
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影响因子：
3.7
作者：
Wicha P;Tocharus J;Janyou A;Jittiwat J;Changtam C;Suksamrarn A;Tocharus C
通讯作者：
Tocharus C
DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
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影响因子：
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