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  

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

作　　者：冉昌丽[1] 李耀彩[1] 

机构地区：[1]三峡大学第一临床医学院宜昌市中心人民医院血液内科,湖北宜昌443003

出　　处：《基础医学与临床》2012年第9期1082-1087,共6页Basic and Clinical Medicine

摘　　要：目的观察解除狭窄联合Rho激酶抑制剂对重度颈动脉狭窄大鼠认知功能(VCI)、海马区细胞凋亡及相关基因表达。方法用48只SD大鼠,复制重度颈动脉狭窄模型,分成假手术组、狭窄解除组、药物组和联合组,另12只为对照组。联合组给予狭窄解除和法舒地尔(8.35 mg/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0.9%氯化钠注射液。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;免疫组化方法检测海马区凋亡相关蛋白BCL-2及BAX免疫阳性细胞数;TUNEL染色法检测海马区凋亡神经细胞。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为56.24%±2.25%,明显低于药物治疗组和狭窄解除组的63.86%±2.23%和61.89%±2.67%(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而明显改善颈动脉狭窄引起的认知功能障碍。Objective To observe combined stenosis removal with Rho kinase inhibitors on severe carotid artery ste- nosis induced VCI model of cognitive function, hippocampal apoptosis and related gene expression. Methods Fourty eight SD rats were divided into： the sham group, narrow discharge group, drug group, combination group, another 12 rats for the control group. Combination group was given a narrow lift and fasudil （8.35 mg/kg） , drug group were injected with 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 treatmentgroup＇s escape latency and the percentage of swimming distance were improved （ P 〈 0. 05 ）, the number of apopto- sisrelated 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 com- bined treatment group was 56. 24%± 2. 25%, greatly decreased compared with drug group and narrow discharge group （63.86% ±2.23% and 61.89% ±2. 67% ,P 〈0. 05）, and with the extension of treatment time, the apop- tosis rate was downward trend. Conclusions Combined stenosis removal with Rho kinase inhibitors could cantly improve stenosis-induced cognitive impairment by signifi adjusting the expression of apoptosis-related proteins.

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 

分 类 号：R749.13[医药卫生—神经病学与精神病学]