2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia.
2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia.
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2-(2-苯并呋喃基)-2-咪唑啉通过调节局灶性脑缺血大鼠模型中神经血管单元的完整性来介导神经保护。
DOI：
10.1016/j.jstrokecerebrovasdis.2017.12.041
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发表时间：
2018-06
影响因子：
2.5
通讯作者：
Ji Xunming
中科院分区：
文献类型：
--
作者：
Zhang Zheng;Zhang Linlei;Chen Jiaou;Cao Yungang;Qu Man;Lin Xinda;Han Zhao;Ji Xunming
我们之前发现，2-（2-苯并呋喃基）-2-咪唑啉（2- bfi）是2型咪唑啉受体（I2R）的配体，通过一种未知的机制在缺血卒中中发挥神经保护作用。本研究采用大鼠90min局灶性脑缺血模型，探讨2-BFI对神经血管单位（NVU）的保护作用。方法将大鼠随机分为3组：假手术组；小鼠对照组和脑中动脉闭塞（MCAO）开始后立即给予2-BFI （3 mg/kg）的2-BFI组。在脑卒中后24 h评估神经功能缺损评分、梗死面积、细胞凋亡水平、脑含水量和Evans Blue外渗。Western blotting检测occludin、occludens小带1 （ZO-1）、collagen IV、aquaporin-4 （AQP-4）、matrix metalloproteinase-9 （MMP-9）、MMP-2的表达。结果2- bfi治疗可显著改善脑卒中后24 h的神经功能，减少梗死面积。2-BFI显著降低细胞凋亡水平（34.3±5.4% vs 56.1±7.9%,p < 0.05）。2-BFI组脑含水量（79.5±2.6% vs 84.62±2%,p < 0.05）显著降低，同侧半球Evans Blue外渗（1.2±0.5 vs 2.5±0.41µg/g, p < 0.05）。2-BFI组occludin、ZO-1、collagen IV表达显著升高，MMP-9表达显著降低。AQP-4和MMP-2在2-BFI组与载药组间无显著差异。结论2-BFI对急性缺血性脑损伤的神经保护作用至少部分是由于其改善NVU功能的能力。
BackgroundWe showed previously that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor (I2R) exerts neuroprotective effects in ischemia stroke via an unknown mechanism. The present study was to investigate whether 2-BFI can protect the neurovascular unit (NVU) using a rat model of 90 min focal cerebral ischemia.MethodsRats were randomly divided into three groups: thesham-operated group; the vehicle control group and the 2-BFI group which received 2-BFI (3 mg/kg) immediately after the start of middle cerebralartery occlusion (MCAO). Neurological deficit score, infarct size, apoptosis level, brain water content and Evans Blue extravasation were assessed at 24 h after stroke. Expressions of occludin and zonula occludens 1 (ZO-1), collagen IV, aquaporin-4 (AQP-4), matrix metalloproteinase-9 (MMP-9) and MMP-2 were assessed by Western blotting.Results2-BFI treatment was associated with significant improvement of neurological performance and decreased infarct volume at 24 h after stroke. Apoptosis level reduced significantly by 2-BFI compared to the vehicle group (34.3 ± 5.4% vs 56.1 ± 7.9%, p < 0.05). Significant decreased of brain water content (79.5 ± 2.6% vs 84.62 ± 2%, p < 0.05) and Evans Blue extravasation (1.2 ± 0.5 vs 2.5 ± 0.41 µg/g, p < 0.05) of ipsilateral hemisphere was observed in 2-BFI group compared to vehicle group. Expressions of occludin, ZO-1 and collagen IV were significantly higher while MMP-9 level significantly lower in 2-BFI group. AQP-4 and MMP-2 showed no difference between 2-BFI and the vehicle groups.ConclusionsThese results suggest that the neuroprotective effects of 2-BFI in acute ischemic brain damage are at least partly due to the drug's ability to improve the functions of NVU.
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影响因子：
5.6
作者：
Liu K;Li Z;Wu T;Ding S
通讯作者：
Ding S
影响因子：
3.3
作者：
G. Sulkowski;B. Dąbrowska-Bouta;M. Chalimoniuk;L. Strużyńska
通讯作者：
G. Sulkowski;B. Dąbrowska-Bouta;M. Chalimoniuk;L. Strużyńska
DOI：
10.1152/ajpheart.00520.2003
发表时间：
2003-12
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
C. D. Sharp;Ian N Hines;J. Houghton;A. Warren;T. H. Jackson;A. Jawahar;Anil Nanda;J. Elrod;A. Long;A. Chi;A. Minagar;J. Alexander
通讯作者：
C. D. Sharp;Ian N Hines;J. Houghton;A. Warren;T. H. Jackson;A. Jawahar;Anil Nanda;J. Elrod;A. Long;A. Chi;A. Minagar;J. Alexander
影响因子：
8.3
作者：
HAMANN, GF;OKADA, Y;DELZOPPO, GJ
通讯作者：
DELZOPPO, GJ
影响因子：
4.5
作者：
Chen, Jui-Tai;Chen, Tyng-Guey;Chen, Ruei-Ming
通讯作者：
Chen, Ruei-Ming