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(carboxymethyl cellulose,CMC)处理组(26只)和Fasudil处理组(25只).首先给予Fasudil(10 mg/kg)或CMC(0.5％ CMC 10ml/kg)处理,然后行脑I/R动物模型缺血60 min后再灌注18 h.氯化三苯四氮唑染色法(2,3,5-tri-phenyltetrazolium chloride,TTC)染色分析脑梗死情况,伊万斯蓝(Evans blue)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) mm3 (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Evans blue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.

abstractsObjective To investigate the neuroprotective effects of Fasudil in cerebral I/R injury in mice.Methods 51 C57BL/6J mice was divided into two groups,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.Compared 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.