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Tempol对慢性脑缺血大鼠脑白质损伤及认知功能的影响 被引量：2

Effects of tempol on white matter lesions and cognitive impairment in a rat model of chronic cerebralhypoperfusion
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摘要 目的观察超氧化物歧化酶类似物Tempol对慢性脑缺血大鼠脑白质损害及认知功能的神经保护作用。方法健康雄性Wistar大鼠采用完全随机数字表法分为假手术组（n=12）、生理盐水组（n=15）、Tempol低剂量组（8mg／kg）组（n：15）和Tempol高剂量组（30mg／kg）组（n=15）。应用大鼠双侧颈总动脉结扎（2-VO）制备慢性脑缺血模型，然后用Morris水迷宫检测各组大鼠的空间学习记忆能力，慢性脑缺血6周后再通过MBP和APP免疫印迹检测脑白质损伤情况，通过测定HNE蛋白加合物了解脂质过氧化情况。结果Tempol降低了慢性脑缺血大鼠的Morris水迷宫实验的潜伏期（P〈0．05）。Tempol低剂量组（0．82±0．17）和Tempol高剂量组（0．91±0．15）大鼠脑白质MBP平均相对光密度较生理盐水组（0．44±0．13）增高（均P〈0．01）。Tempol低剂量组（0．55±0．13）和Tempol高剂量组（0．46±0．15）大鼠脑白质APP平均相对光密度较生理盐水组（0．96±0．19）降低（均P〈0．01）。Tempol低剂量组（0．20±0．035）和Tempol高剂量组（0．18±0．031）大鼠脑白质HNE蛋白加合物平均相对光密度较生理盐水组（0．29±0．039）降低（均P〈0．01）。结论抗氧化剂Tempol可能通过保护慢性缺血性脑白质损伤而改善大鼠的学习记忆能力，并且Tempol减少脂质过氧化物的形成可能是其保护慢性缺血性脑白质损伤的机制之一。 Objective To assess the neuroprotective effect of Tempol, an antioxidant acting as a superoxide dismutase mimic, on white matter lesions and cognitive impairment in rats with chronic cerebral hypoperfusion. Methods Chronic cerebral ischemia was induced by permanent occlusion of bilateral common carotid arteries （2-VO） in male Wistar rats. The animals were divided into sham operation, saline- treated, Tempol （8 mg/kg） and Tempol （30 mg/kg） groups （n = 15 each）. Performance of Morris water maze task and Western blot for myelin basic protein （ MBP）, amyloid precursor protein （APP） and 4- hydroxy-2-nonenal （HNE） modified proteins were analyzed at 6 weeks post-hypoperfusion. Results Tempol reduced the escape latency of Morris water maze post-hypoperfusion in comparison with the saline- treated rats （P 〈 0. 05 ）. The mean relative optical density of MBP in the white matter was significantly higher in Tempol （8 mg/kg） group （0. 82 ±0. 17） and Tempol （30 mg,/kg） group （0. 91 ± 0. 15） than saline-treated group （0. 44±0. 13, all P 〈0. 01 ）. The mean relative optical density of APP in white matter was significantly lower in Tempol （8 mg/kg） group （0. 55 ±0. 13） and Tempol （30 mg/kg） group （0. 46 ± 0. 15 ） than saline-treated group （0.96 ± 0. 19, all P 〈 0. 01 ）. The mean relative optical density of HNE- modified protein in white matter was significantly lower in Tempol （8 mg/kg） group （0. 20±0. 035 ） and Tempol （30 mg/kg） group （0. 18±0. 031 ） than saline-treated group （0. 29±0. 039, all P 〈 0. 01 ）. Conclusion Tempol ameliorates cognitive impairment by preventing white matter lesions induced by chronic cerebral hypoperfusion in rats. And it may protect white matter lesions in hypoperfused rats through reducing the formation of lipid peroxidation.
作者 刘汉兴 章军建 张磊 刘晖
机构地区 武汉大学中南医院神经科
出处 《中华医学杂志》 CAS CSCD 北大核心 2013年第17期1330-1334,共5页 National Medical Journal of China
基金 国家自然科学基金（81171029）
关键词 TEMPOL 脑白质损害 认知障碍 Tempol White matter lesions Cognition disorders
分类号 R743 [医药卫生—神经病学与精神病学]
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参考文献18

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二级参考文献15

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共引文献9

同被引文献19

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中华医学杂志
2013年 第17期

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