Gao Yong, Zhao Yun, Pan Jingzi, Yang Liu, Huang Tingting, Feng Xiaomin, Li Chao, Liang Shujing, Zhou Dingfu, Liu Chan, Tu Fengxia, Tao Cai, Chen Xiang
Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Experimental Medicine Section, NIDCR, National Institutes of Health, Bethesda, MD 20892-4322, USA.
Brain Res. 2014 Oct 17;1585:83-90. doi: 10.1016/j.brainres.2014.08.032. Epub 2014 Aug 19.
The purpose of this study was to investigate the role of caveolin-1 in treadmill-exercise-induced angiogenesis in the ischemic penumbra of rat brains, and whether caveolin-1 changes correlated with reduced brain injury induced by treadmill exercise, in rats after cerebral ischemia. Rats were randomized into five groups: sham-operated (S, n=7), model (M, n=36), exercise and model (EM, n=36), inhibitor and model (IM, n=36), and inhibitor, exercise, and model (IEM, n=36). Rats in the model groups underwent middle cerebral artery occlusion (MCAO). Rats in the inhibitor groups received an IP injection of the caveolin-1 inhibitor, daidzein (0.4 mg/kg), every 24 h following reperfusion. Rats were killed at 7 or 28 days after the operation. The exercise group showed better neurological recovery and smaller infarction volumes compared with the non-exercise group. Correspondingly, significant increases of caveolin-1 and vascular endothelial growth factor (VEGF) protein expression were observed compared with the non-exercise group. Additionally, the number of Flk-1/CD34 double-positive cells towards the ischemic penumbra was increased in the exercise group. Furthermore, the induction of VEGF protein, microvessel density, decrease of infarct volumes and neurological recovery was significantly inhibited by daidzein. This study indicates that treadmill exercise reduces brain injury in stroke. Our findings suggest that the caveolin-1 pathway is involved in the regulation of VEGF in association with promoted angiogenesis in the ischemic penumbra of rat brains after treadmill exercise. The caveolin-1/VEGF signaling pathway may be a potential target for therapeutic intervention in rats following MCAO.
本研究旨在探讨小窝蛋白-1在大鼠脑缺血半暗带跑步机运动诱导的血管生成中的作用，以及小窝蛋白-1的变化是否与跑步机运动诱导的脑损伤减轻相关。将大鼠随机分为五组：假手术组（S，n = 7）、模型组（M，n = 36）、运动加模型组（EM，n = 36）、抑制剂加模型组（IM，n = 36）和抑制剂、运动加模型组（IEM，n = 36）。模型组大鼠进行大脑中动脉闭塞（MCAO）。抑制剂组大鼠在再灌注后每24小时腹腔注射小窝蛋白-1抑制剂大豆苷元（0.4 mg/kg）。术后7天或28天处死大鼠。与非运动组相比，运动组神经功能恢复更好，梗死体积更小。相应地，与非运动组相比，观察到小窝蛋白-1和血管内皮生长因子（VEGF）蛋白表达显著增加。此外，运动组中向缺血半暗带迁移的Flk-1/CD34双阳性细胞数量增加。此外，大豆苷元显著抑制了VEGF蛋白的诱导、微血管密度、梗死体积的减小和神经功能恢复。本研究表明跑步机运动可减轻中风后的脑损伤。我们的研究结果表明，小窝蛋白-1途径参与了VEGF的调节，并与跑步机运动后大鼠脑缺血半暗带血管生成的促进有关。小窝蛋白-1/VEGF信号通路可能是MCAO大鼠治疗干预的潜在靶点。
