基础医学与临床 ›› 2012, Vol. 32 ›› Issue (9): 1082-1087.

• 研究论文 • 上一篇    下一篇

解除狭窄联合Rho激酶抑制剂对颈动脉狭窄大鼠认知功能的影响

冉昌丽,李耀彩   

  1. 湖北省宜昌市三峡大学第一临床医学院
  • 收稿日期:2011-02-17 修回日期:2011-12-04 出版日期:2012-09-05 发布日期:2012-08-28
  • 通讯作者: 李耀彩 E-mail:yaocaili@126.com

Effects of combined stenosis removal with Rho kinase inhibitors on cognitive function of rats with carotid artery stenosis

  • Received:2011-02-17 Revised:2011-12-04 Online:2012-09-05 Published:2012-08-28

摘要: 目的 观察解除颈动脉狭窄联合Rho激酶抑制剂对重度颈动脉狭窄所致大鼠VCI模型认知功能、海马区细胞凋亡情况及相关基因表达的干预作用。方法 取SD大鼠60只,制作重度颈动脉狭窄模型,将其随机分成5组:联合组、药物组、狭窄解除组、对照组和假手术组。联合组给予狭窄解除和法舒地尔(8.35mg/kg),药物组注射等量的法舒地尔,狭窄解除组给予解除狭窄,对照组注射等容积的生理盐水。分别在干预2和4周后,Morris 水迷宫实验检测大鼠的空间学习记忆能力;免疫组化方法分析海马区凋亡相关蛋白Bcl-2及Bax免疫阳性细胞数的变化;TUNEL染色法检测海马区神经细胞的凋亡。结果:与单纯药物组和狭窄解除组比较,联合治疗组大鼠的逃避潜伏期和游泳距离百分比均有显著改善(P<0.05),海马区凋亡相关蛋白Bcl-2免疫阳性细胞数显著增加(P<0.05),而Bax的免疫阳性细胞数显著降低(P<0.05),且治疗4周比2周更明显(P<0.05);联合治疗组大鼠海马区的神经细胞凋亡率有显著下降(P<0.05),且随着治疗时间延长,细胞凋亡率呈下降趋势。结论:解除颈动脉狭窄联合Rho激酶抑制剂可通过调节凋亡相关蛋白的表达从而明显改善颈动脉狭窄引起的认知功能障碍。

关键词: 血管性认知障碍, Rho激酶抑制剂, 细胞凋亡, 颈动脉支架成形术

Abstract: Objective To observe the intervention effect of the removing carotid artery stenosis combined with Rho kinase inhibitors on severe carotid artery stenosis induced VCI model of cognitive function, hippocampal apoptosis and related gene expression. Method 60 SD rats which were made into severe carotid stenosis model were randomly divided into five groups: combination group, drug group, narrow discharge group , control group and the sham group. Combination group was given a narrow lift and fasudil (8.35mg/kg), drug group were injected the same amount of fasudil, narrow discharge group were lifted the narrow, and the control group was injected with equal volume of saline. In 2, 4 weeks after the intervention, the spatial learning and memory ability of rats were measured by Morris water maze; analysed the expression of apoptosis-related protein Bcl-2 and Bax in hippocampus by immunohistochemistry and detecting the apoptosis of hippocampal nerve cells by TUNEL staining. Results Compared with the simple drug group and narrow discharge group, the combined treatment group’s escape latency and the percentage of swimming distance were improved (P <0.05), the number of apoptosis-related protein Bcl-2 positive cells was increased while the Bax positive cells was reduced (P <0.05), and 4 weeks is more pronounced than two weeks (P <0.05), neuronal apoptosis rate of hippocampus District in combined treatment group decreased(P <0.05), and with the extension of treatment time, the apoptosis rate was downward trend.Conclusion Combined stenosis removal with Rho kinase inhibitors could significantly improve stenosis-induced cognitive impairment by adjusting the expression of apoptosis-related proteins .

Key words: Vascular Cognitive Impairment, Rho kinase inhibitors, Apoptosis, Carotid Artery Stenting

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