摘要
目的探讨藻蓝蛋白在脑缺血再灌注损伤过程中的神经保护作用机制。方法成年健康雄性Wistar大鼠52只,应用线栓法建立大脑中动脉阻塞再灌注(MCAO/R)模型,应用藻蓝蛋白进行治疗,观察脑缺血再灌注后神经细胞凋亡,碱性成纤维细胞生长因子(bFGF)及其受体(FGFR-1)、胰岛素样生长因子(IGF-1)及其受体(IGF-1R)、诱导型一氧化氮合酶(iNOS)和超氧化物歧化酶(SOD)表达,以及藻蓝蛋白对上述指标的影响。结果①脑缺血再灌注损伤后,动物出现不同程度的神经功能障碍,缺血损伤区神经细胞数量减少,凋亡细胞增多。藻蓝蛋白治疗组再灌注12h^3d细胞凋亡数量明显减少,再灌注7~14d动物神经功能恢复明显优于对照组。②对照组皮质区和纹状体区bFGF和FGFR-1表达自缺血再灌注6h逐渐增强,1d达高峰,之后逐渐减弱。治疗组bFGF和FGFR-1阳性细胞数量较对照组相应时间点增加,分别于再灌注1d和12h^3d有显著性差异。③脑缺血后神经细胞IGF-1和IGF-1R表达增强,主要位于皮层区和纹状体区。经藻蓝蛋白治疗后,各时间点IGF-1和IGF-1R阳性细胞数量较对照组有所增加,其中再灌注6h^1d有显著性差异。④缺血再灌注后皮质区和纹状体区iNOS和SOD表达增强,再灌注6h^7d维持较高的水平,1d达高峰。治疗组iNOS表达降低,而SOD表达增强,其中iNOS于12h^1d,SOD于6h^1d与对照组同一时间点比较有显著性差异。结论藻蓝蛋白可能通过上调SOD和下调iNOS表达激活内源性抗氧化机制而发挥抗凋亡作用,通过诱导内源性bFGF和IGF-1及其相关受体的表达促进神经细胞修复。
Objective To investigate the neuroprotective effects and mechanism of phycocyanin in cerebral ischemia reperfusion injury in rats. Methods The model of middle cerebral artery occlusion reperfusion （MCAO/R） was established using the intraluminal filament occlusion with healthy adult male Wistar rats treated by phycocyanin. The apoptosis and the expression of bFGF and FGFR-1, IGF-1 and IGF-1R, iNOS and SOD were respectively determined by TUNEL and immunohistochemical staining to evaluate the effects of phycocyanin on above indexes. Results ①The rats showed neurobehavioral function disorders and the number of nerve cells reduced while apoptotic cells increased in ischemic area after ischemic reperfusion. In phycocyanin group, the number of apoptotic cells reduced siginificantly during reperfusion 12h-3d and the neurobehavioral function was better than that those in control group during reperfusion 7-14d. ②In control group, the expressions of bFGF and FGFR-1 increased successfully from reperfusion 6h and reached a maximum at 1d, then subsided gradually in cortex and striatum. In phycocyanin group, the numbers of bFGF and FGFR-1 positive cells were higher than those in control group at the same time-points, which were significantly at reperfusion ld and 12h-3d respectively. ③The expressions of IGF-1 and IGF-1R increased in cortex and striatum following cerebral ischemic and reperfusion. In phycocyanin group, the numbers of IGF-1 and IGF-1R positive cells in each time-point were higher than those in control group, which was significantly during reperfusion 6h-1d. ④ In cotex and striatum, the iNOS and SOD expressed strongly and keep high level during 6h-7d with the maximum at reperfusion ld. in phycocyanin group, iNOS expressed significantly higher during 12h-1d whlie SOD lower during 6h-1d than those in control group at the same time-point. Conclusion Phycocyanin might play a intrinsic antioxide effect by up-regulating SOD and down-regulating iNOS to inhibit neuronal apoptosis, and enhance the neuronal repairation by means of inducing the expressions of bFGF and IGF-1 following cerebral ischemic reperfusion in rats.
出处
《中国海洋药物》
CAS
CSCD
2006年第6期20-25,共6页
Chinese Journal of Marine Drugs
