摘要
目的探讨盐酸帕罗西汀的神经保护作用及其可能的分子生物学机制,为今后的进一步开发研究和临床治疗提供实验依据。方法 75只大鼠随机分为假手术组、阴性对照组和药物干预组。采用改良Longa.Zea线栓法[1]制作脑缺血再灌注模型后,阴性对照组予生理盐水灌胃;药物干预组盐酸帕罗西汀灌胃;假手术组不给药。参照改良的神经功能缺损评分方法(modify neurological severity scores,m NSS)对各组大鼠进行神经功能评分,通过激光共聚焦检测各组大鼠缺血区脑组织的血管新生情况,并检测血管内皮生长因子(VEGF)的表达情况。结果 1术后14 d,药物干预组的毛细血管直径显著小于阴性对照组和假手术组,血管密度及缺血区微血管总面积显著高于假手术组和阴性对照组,差异均有统计学意义(P<0.01)。2术后14 d,假手术组大鼠m NSS评分变化不大,而阴性对照组和药物干预组的m NSS评分都有不同程度下降,药物干预组明显低于阴性对照组,差异有统计学意义(P=0.015)。3术后14 d,药物干预组血浆VEGF浓度>阴性对照组>假手术组,两两比较,差异有统计学意义(P<0.001)。4VEGF阳性细胞具有神经元的形态特征,主要分布在大脑皮质、海马和纹状体等脑区。结论大鼠脑缺血再灌注后,盐酸帕罗西汀能够促进VEGF表达并改善大鼠脑缺血再灌注后的神经行为学功能,从而起到脑保护作用。
Objective To investigate the neuron-protective effect of paroxetine and the possible molecular mechanisms in order to provide experimental basis for the further research and development and clinical treatment. Methods Seventy-five rats were random- ly divided into sham group, negative control group and intervention group. After set-up a cerebral ischemia-reperfusion model by using a modified Longa. Zea method, saline and paroxetine were intragastrically administrated in the negative and intervention groups, respec- tively while no treatment was applied to the sham group. The never function was assessed by using a modified neurological severity scores （mNSS）. The angiogenesis in ischemie brain tissue was measured by using a confocal laser. The expression of vascular endotheli- al growth factor（VEGF） was also detected. Results ①After 14 days of operation, capillary diameter was obviously smaller while vascu- lar density and micro vascular total area in the ischemic area were significantly higher in the intervention group than that in the negative and sham groups. ②After 14 days of operation,no significant change in mNSS was found in the sham group while mNSS was decreased in the negative or intervention groups. The decrease was much lower in the intervention group than that in the negative group （ P = 0. 015 ）. ③After 14 days of operation, plasma VEGF concentrations were different among the groups and there were statistical signifi- cances in two pair comparison（ P 〈 0. 0001 ）. ④VEGF-positive ceils showed morphological characteristics of neurons which mainly dis- tributed in the cerebral cortex, hippocampus and striatum and other brain regions. Conclusion After cerebral isehemia reperfusion, paroxetine hydrochloride can promote VEGF expression and improve neurological behavior of rats, and thus play a protective role in the brain.
出处
《实用医院临床杂志》
2014年第6期24-27,共4页
Practical Journal of Clinical Medicine
关键词
帕罗西汀
缺血性脑血管病
动物实验
修复神经组织
Paroxetine
Ischemic cerebrovascular disease
Animal experiments
Nerve tissue repairmen
