DIOSMIN PROTECTS AGAINST CEREBRAL ISCHEMIA/REPERFUSION INJURY THROUGH ACTIVATING JAK2/STAT3 SIGNAL PATHWAY IN MICE
DIOSMIN PROTECTS AGAINST CEREBRAL ISCHEMIA/REPERFUSION INJURY THROUGH ACTIVATING JAK2/STAT3 SIGNAL PATHWAY IN MICE
复制标题
地奥司明通过激活小鼠 JAK2/STAT3 信号通路来防止脑缺血/再灌注损伤
DOI：
10.1016/j.neuroscience.2014.03.032
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发表时间：
2014-05-30
期刊：
影响因子：
3.3
通讯作者：
Wang, X.
中科院分区：
文献类型：
--
作者：
Liu, X.;Zhang, X.;Wang, X.
背景与目的：细胞凋亡是脑缺血/再灌注（I/R）发病机制中细胞死亡的一种主要形式，可能是一个治疗靶点。地奥司明（DM）是一种微粉化的纯化黄酮类药物，在治疗静脉曲张和肾损伤中具有抗凋亡作用。然而，DM在脑I/R急性期的作用尚不明确。本研究探讨了DM在脑I/R中的作用及其潜在机制。
方法：雄性CD - 1小鼠接受大脑中动脉短暂闭塞（tMCAO）。实验1用于评估脑I/R后Janus酪氨酸激酶 - 2（JAK2）、信号转导和转录激活因子 - 3（STAT3）、磷酸化JAK2（pJAK2）和磷酸化STAT3（pSTAT3）的时间进程表达，包括6个时间点。在实验2中，在接受tMCAO之前，小鼠连续6天以50mg/kg或100mg/kg的剂量口服DM。再灌注24小时后，检查神经功能缺损、尼氏染色、脑含水量和梗死体积。通过免疫组织化学、实时定量聚合酶链反应（qRT - PCR）和蛋白质印迹法检测Bcl - 2、Bax、pJAK2和pSTAT3。使用共聚焦显微镜观察pSTAT3在大脑皮质中的位置。
结果：与溶媒组相比，高剂量的DM显著减轻神经功能缺损、脑含水量和梗死体积，增加尼氏阳性细胞数量，上调pJAK2、pSTAT3和Bcl - 2的表达，下调Bax的表达（P < 0.05）。
结论：这些结果表明，DM通过激活JAK2/STAT3信号通路来预防脑I/R损伤。（C）2014国际脑研究组织。由爱思唯尔有限公司出版。保留所有权利。
Background and object: Apoptosis is a major form of cell death in cerebral ischemia/reperfusion (I/R) pathogenesis and may represent a target for treatment. Diosmin (DM), a micronized purified flavonoid drug, possesses an anti-apoptotic effect in the treatment of varicose veins and renal injury. However, the effect of DM in the acute phase of cerebral I/R is not clear. This study investigated DM's role in cerebral I/R and its potential mechanism.Methods: Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO). Experiment 1 was used to evaluate the time course expression of Janus tyrosine kinase-2 (JAK2), signal transducer and activator of transcription-3 (STAT3), phosphorylated JAK2 (pJAK2) and phosphorylated STAT3 (pSTAT3) after cerebral I/R, and six time points were included. In experiment 2, DM was given orally at doses of 50 mg/kg or 100 mg/kg for 6 consecutive days before receiving tMCAO. At 24 h after reperfusion, neurological deficit, Nissl staining, brain water content and infarct volume were examined. Bcl-2, Bax, pJAK2, and pSTAT3 were detected by immunohistochemistry, qRT-PCR and Western blot. Confocal microscope was used to observe the location of pSTAT3 in the cerebral cortex.Results: Compared with Vehicle group, the high dose of DM significantly alleviated neurological deficit, brain water content, infarct volume, increased the Nissl-positive cells, upregulated the expression of pJAK2, pSTAT3 and Bcl-2 and downregulated Bax (P < 0.05).Conclusion: These results showed that DM protected against cerebral I/R injury through activating JAK2/STAT3 signal pathway. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.