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法舒地尔对小鼠脑缺血再灌注损伤保护作用的血脑屏障机制 被引量:3

The neuroprotective effects of Fasudil on brain ischemia/reperfusion injury through maintaining blood-brain barrier function
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摘要 目的探讨法舒地尔(Fasudil)在小鼠脑缺血再灌注(Ischemia/reperfusion,I/R)损伤中的神经保护作用。方法51只c57BL/6J小鼠随机分为两组,羟甲基纤维素(carboxymethylcellulose,CMC)处理组(26只)和Fasudil处理组(25只)。首先给予Fasudil(10mg/kg)或CMC(0.5%CMC10ml/kg)处理,然后行脑I/R动物模型缺血60min后再灌注18h。氯化三苯四氮唑染色法(2,3,5-triphenyhetrazoliu mchloride,rrc)染色分析脑梗死情况,伊万斯蓝(Evansblue)和白蛋白(Albumin)免疫印迹分析血脑屏障通透性的改变,酶谱法检测MMP9活性变化。结果在小鼠脑I/R动物模型中CMC组的脑坏死体积为(99.07±6.53)mm3,Fasudil组的脑坏死体积为(57.02±8.93)mm。(P〈0.01);Fasudil处理组I/R小鼠血液中MMP9活性低于CMC处理组;与CMC处理组相比,Fasudil处理组的脑组织中Albumin和Evansblue相对含量分别从(2.95±0.77),(5.15±0.24)减少到(1.04±0.18),(1.96±0.31)(均P〈0.01)。结论Fasudil通过抑制MMP9活性以维持血脑屏障通透性,从而保护I/R损伤。 Objective To investigate the neuroprotective effects of Fasudil in cerebral I/R injury in mice. Methods 51 C57BL/6J mice was divided into two grnups,CMC treated group (n=26) and Fasudil treated group (n=25) ,randomly. The mice were treated with Fasudil (10 mg/kg) or CMC (0.5% CMC 10 ml/kg) separately. Then the treated mice were subjected to 60 min of focal ischemia and 18 h reperfusion. The infarct volume of brain was analyzed by TTC staining with MCID image system. BBB permeability was assessed by Evans blue extravasation and albumin leakage which was detected by immuno-blotting assay. The activity of MMP9 was analyzed by zymography. Results The infarct volume in CMC group ((99.07±6.53) mm3) was larger than that in Fasudil group ((57.02±8.93)mm3) ,the difference was statistically significant (P〈0.01) .The activity of MMP9 in the mice treated with Fasudil was lower than that in CMC group. Com- pared with the CMC group( albumin (2.95±0.77),Evans blue (5.15±0.24)), the albumin and Evans blue content in the Fasudil treated group ( albumin ( 1.04 ± 0.18 ), Evans blue ( 1.96 ± 0.31 ) ) reduced significanctly (all P〈 0.01 ). Conclusion Fasudil protects I/R damage by inhibiting the activity of MMP9 to maintain blood-brain barrier permeability.
出处 《中华行为医学与脑科学杂志》 CAS CSCD 北大核心 2017年第10期933-937,共5页 Chinese Journal of Behavioral Medicine and Brain Science
基金 国家自然科学基金项目(81360206) 云南省中青年学术技术带头人后备人才基金项目(2014HB025) 云南省教育厅科研基金项目(2015Y379)
关键词 脑缺血 法舒地尔 伊万斯蓝 白蛋白 血脑屏障 Ischemia Fasudil Evans blue Albumin Blood brain barrier (BBB)
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