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目的研究经鼻给予酸性成纤维细胞生长因子(acidic fibroblast growth factor,aFGF)对脑梗死后神经和血管再生及神经功能恢复的影响。方法健康雄性SD大鼠30只,随机分为aFGF组(n=12)、对照组(n=12)和假手术组(n=6);aFGF组和对照组大鼠建立大脑中动脉闭塞模型,脑缺血再灌注24h后经鼻分别给予10μg aFGF(200μl)和等容积生理盐水,1次/d,连续7d;同时腹腔注射5-溴脱氧尿核苷(Bromode-oxyuridine,BrdU)50mg/kg,1次/d,连续13d;假手术组操作过程和给药与对照组相同,但不用线栓阻塞大脑中动脉;分别在术前和术后第1、7、14d采用改良神经功能评分评价大鼠神经功能改变情况,并于术后第14d经尾静脉注入异硫氰酸荧光素右旋糖酐(FITC-dextran),采用免疫组化及激光共聚焦方法分别检测梗死灶周、室管膜下区和纹状体BrdU阳性细胞及微血管的数量。结果术后第7及14d aFGF组神经功能评分显著低于对照组;术后第14d aFGF组缺血侧室管膜下区和纹状体BrdU阳性细胞数与对照组相比均显著增高(P<0.01),假手术组仅见少量BrdU阳性细胞;激光共聚焦显示aFGF组梗死灶周微血管数较对照组显著增加(P<0.05);同时,与对照组相比经鼻给予aFGF能增加BrdU阳性细胞在血管内皮细胞中的百分比,且有统计学意义(P<0.05)。结论经鼻给予aFGF能有效促进神经和血管再生,改善脑缺血后神经功能评分,对于治疗脑梗死具有潜在的应用前景。
Objective To investigate the effect of nasal administration of acidic fibroblast growth factor (aFGF) on the neural and angiogenesis and the recovery of neurological function after cerebral infarction. Methods Thirty healthy male Sprague-Dawley rats were randomly divided into aFGF group (n = 12), control group (n = 12) and sham operation group (n = 6). Middle cerebral artery occlusion model was established in aFGF group and control group , 24h after cerebral ischemia and reperfusion, 10μg aFGF (200μl) and normal saline were given to the rats intranasally once a day for 7 days. Bromode-oxyuridine (BrdU) 50mg / kg once a day for 13 days. The operation and administration of the sham-operation group were the same as those of the control group, but no occlusion of middle cerebral artery occlusion was performed in the sham operation group. The improved neurological function score The changes of neurological function in rats were evaluated. FITC-dextran was injected through the caudal vein 14 days after operation. The expression of FITC-dextran was detected by immunohistochemistry and laser scanning confocal microscope. District and striatum BrdU positive cells and the number of microvessels. Results The neurological scores of aFGF group were significantly lower than those of the control group on the 7th and 14th day after operation. The number of BrdU positive cells in the subventricular zone and striatum of the aFGF group was significantly higher than that of the control group on the 14th day (P < 0.01). Only a small amount of BrdU positive cells were observed in the sham operation group. Laser confocal analysis showed that the number of microvessels in the aFGF group was significantly increased compared with the control group (P <0.05), and the nasal administration of aFGF increased the number of BrdU positive cells The percentage in vascular endothelial cells was statistically significant (P <0.05). Conclusion Nasal administration of aFGF can effectively promote the regeneration of nerve and blood vessel and improve the score of neurological function after cerebral ischemia, which has potential application in the treatment of cerebral infarction.