西酞普兰促进血管发生对脑缺血再灌注大鼠的神经保护作用

Neuroprotective effect of esdtalopram on cerebral ischemia/reperfusion in rats by promoting angiogenesis

目的探讨西酞普兰对局灶性脑缺血再灌注大鼠的神经保护作用及其可能机制。方法75只雄性sprague—Dawley大鼠随机分为假手术组、生理盐水对照组和西酞普兰干预组，每组25只。线栓法制作大鼠局灶性脑缺血再灌注模型。改良神经功能缺损量表评价大鼠神经功能缺损（每组5只）。激光共聚焦技术观察缺血区微血管直径、密度和总面积（每组5只）。酶联免疫吸附法检测血浆血管内皮生长因子（vascular endothelial growth factor，VEGF）浓度（每组5只）。免疫组织化学染色法（每组5只）和蛋白质印迹法（每组5只）检测缺血脑组织VEGF表达。结果模型制作后14d时，西酞普兰干预组神经功能缺损较生理盐水对照组显著改善[（4．39±0．92）分对（6．57±1．13）分，P=0．015]。三维共聚焦血管成像显示，西酞普兰干预组毛细血管直径显著性小于生理盐水对照组[（2．93±0．19）μm对（3．56±0．22）μm；P=0．000]；血管密度显著性高于生理盐水对照组[（232．68±12．54）个／0．002一对（176．26±10．87）个／0．002mm3；P=0．000]；微血管总面积显著性大于生理盐水对照组[（89154±3298）μm2／0．002耐对（75368．14±3519）μm2／0．002mm3；P=0．000]。酶联免疫吸附法显示，西酞普兰干预组血浆VEGF浓度显著性高于生理盐水对照组[（50．35±5．44）pg／ml对（13．75±4．12）pg／ml；P=0．000]。免疫组织化学分析显示，西酞普兰干预组缺血区VEGF表达显著性高于生理盐水对照组（P=0．000）。蛋白质印迹法显示，西酞普兰干预组缺血脑组织VEGF表达显著性高于生理盐水对照组[（0．94±0．18）对（0．62±0．22）；P=0．006]。结论西酞普兰可显著减轻脑缺血再灌注大鼠的神经功能缺损，其机制可能与VEGF介导的血管发生有关。

Objective To investigate the neuroprotective effect of escitaloprarn on focal cerebral ischemia/ reperfilsion in rats and its possible mechanisms. Methods Seventy-five male Sprague-Dawley rats were randomly divided into three groups： sham operation, saline control and escitalopram intervention groups （n = 25 in each group）. A focal cerebral ischemia reperfusion model in rats was induced by the intraluminal suture method. The modified neurological severity scale was used to evaluate neurological deficit in rats （n = 5 in each group）. Laser confocal technology was used to observe the microvascular diameter, density, and total area in ischemic region （n = 5 in each group）. Enzyme-linked immunosorbent assay was used to detect the plasma concentration of vascular endothelial growth factor （VEGF） （n = 5 in each group）. [mmunohistochemical staining （n = 5 in each group） and Western blotting （n = 5 in each group） were used to detect the expression of VEGF in the ischemic brain tissue. Results At day 14 after modeling, the neurological deficit improved more significantly in the escitalopram intervention group than that in the saline control group （4. 39 ±0. 92 vs. 6. 57± 1.13; P =0. 015）. The 3D confocal vascular imaging showed that capillary diameter in the escitalopmm intervention group was significantly smaller than that in the saline control group （2. 93 ± 0. 19μm vs. 3.56 ± 0. 22 μm; P 〈 0. 01）; the vascular density was significantly higher than that in the saline control group （232. 68-± 12. 54/0. 002 mm3 vs. 176. 26 ± 10. 87/0. 002mm3; P =0. 000）; the total microvascular area was significantly greater than that in the saline control group （89 154± 3 298 μm2/0.002 mm3 vs. 75 368. 14± 3 519μm2/0. 002 mm3; P= 0. 000）. Enzyme-linked immunosorbent assay showed that the plasrtm VEGF concentration in the escitalopram intervention goup was significantly higher than that in the saline control group （50. 35 ± 5.44 pg/ml vs. 13.75 ± 4. 12 pg/ml; P = 0. 000）. Immunohistochemical analysis showed that the VEGF expression in ischemic brain tissue in the escitalopram intervention group was sigrhficantly higher than that in the saline control group （P = 0. 000）. Western blotting showed that the VEGF expression in ischemic brain tissue in the escitalopram intervention group was sigfificantly higher than that in the saline control group （0. 94 ±0. 18 vs. O. 62 ±0. 22; P =0. 006）. Conclusions Escitalopram may reduce neurological deficit in cerebral ischemia/reperfusion in rats. Its mechanisms may be associated with VEGF-mediated angiogenesis.