Stavchanskiĭ V V, Tvorogova T V, Botsina A Iu, Skvortsova V I, Limborskaia S A, Miasoedov N F, Dergunova L V
Mol Biol (Mosk). 2011 Nov-Dec;45(6):1026-35.
Neurotrophins regulate key function of nervous tissue cells. Analysis of neurotrophins mRNA expression is an appropriate tool to assess therapeutic efficiency of the anti-stroke drugs. We have analyzed the effect of synthetic peptide semax and its C-terminal Pro-Gly-Pro tripeptide upon mRNAs expression of neurotrophins Ngf, Bdrf, Nt-3 and their receptors TrkA, TrkB, TrkC, p75 in rat frontal lobes, hippocampus and cerebellum after bilateral common carotid artery occlusion. The animals were decapitated 30 min, 1, 2, 4, 8, 12, 24 h after the operation. The mRNA expression of neurotrophins and their receptors was assessed by relative quantification using real-time RT-PCR. Our showed that ischemia causes a significant decrease in gene expression in the hippocampus. Semax and PGP affected the expression of neurotrophins and their receptors predominantly in the frontal cortex and hippocampus of the ischemized animals. In the frontal cortex, Semax treatment resulted in a decrease of mRNA level of receptors, while PGP treatment increased the level of these mRNA. Maximal neuroprotective effect of both peptides has been observed in the hippocampus 12 h after occlusion. A decrease of gene expression of neurotrophins and their receptors caused by the occlusion was overcome by Semax and PGP. These results clarify the semax mechanism of and present certain features of mRNA's expression of neurotrophins and their receptors in experimental conditions.
神经营养因子调节神经组织细胞的关键功能。分析神经营养因子mRNA表达是评估抗中风药物治疗效果的合适工具。我们分析了合成肽赛玛新(Semax)及其C端脯氨酰-甘氨酰-脯氨酸三肽(PGP)对双侧颈总动脉闭塞后大鼠额叶、海马和小脑中神经营养因子Ngf、Bdrf、Nt-3及其受体TrkA、TrkB、TrkC、p75 mRNA表达的影响。术后30分钟、1、2、4、8、12、24小时将动物断头。使用实时逆转录聚合酶链反应(RT-PCR)通过相对定量评估神经营养因子及其受体的mRNA表达。我们的研究表明缺血导致海马中基因表达显著下降。赛玛新和PGP主要影响缺血动物额叶皮质和海马中神经营养因子及其受体的表达。在额叶皮质中,赛玛新治疗导致受体mRNA水平降低,而PGP治疗则增加了这些mRNA的水平。在闭塞后12小时,在海马中观察到两种肽的最大神经保护作用。赛玛新和PGP克服了由闭塞引起的神经营养因子及其受体基因表达的下降。这些结果阐明了赛玛新的作用机制,并呈现了实验条件下神经营养因子及其受体mRNA表达的某些特征。