Tempol对卒中易感型自发性高血压模型大鼠脑小血管病发病的影响  

Effect of Tempol on cerebral small vessel disease in spontaneously hypertensive stroke-prone rats

作　　者：王子高[1] 杨雅松[1] 徐逸轩 祖衡兵[1] 

机构地区：[1]复旦大学附属金山医院神经内科,上海201508

出　　处：《神经解剖学杂志》2016年第3期288-292,共5页Chinese Journal of Neuroanatomy

基　　金：上海市金山区卫计委青年项目(JSKJ-KTQN-2014-08)

摘　　要：目的:探讨Tempol对脑小血管病变卒中发生的影响。方法:以卒中易感型自发性高血压大鼠(SHRSP)为脑小血管病动物模型,将其随机分为对照组与Tempol处理组,每组10只。利用行为学观察评估卒中事件的发生率及大鼠的存活率,Elisa法测定额叶皮层丙二醛(MDA)的含量、总抗氧化能力(TAC)及超氧化物歧化酶(SOD)的活性,Evans blue染色测定血脑屏障的破坏程度,Western Blot测定紧密连接蛋白occludin、claudin-5与Zo-1的表达。结果:与对照组相比,Tempol处理组首次卒中发病时间推迟(36 d vs 20 d,P<0.05),卒中发病率下降(75%vs 100%,P<0.05),存活率提高(45%vs 25%,P<0.05)。Tempol处理组额叶皮层MDA含量(nmol/mg)降低(0.63±0.04 vs1.23±0.07,P<0.05),TAC与SOD酶活性(U/mg)增加(25.6±3.4 vs 15.6±1.2,P<0.05;7.46±0.92 vs 5.2±0.7,P<0.05)。Tempol处理组额叶皮层Evans blue含量(μg/mg)降低(3.75±0.42 vs 6.16±0.34,P<0.05),且伴有occludin、claudin-5与Zo-1蛋白表达增加。结论:Tempol可通过抑制氧化应激,减轻血脑屏障破坏,降低大鼠脑小血管病卒中发生风险。Objective： To explore the protective effect of Tempol against stroke in cerebral small vessel disease.Methods： Spontaneously hypertensive stroke-prone rats（ SHRSP） were used as the model of cerebral small vessel disease. Twenty SHRSP rats were randomly assigned to vehicle group and Tempol group,with ten rats in each group. Incidence of stroke and survival ratio of SHRSP rats was observed by behavior test. Levels of malondialdehyde（ MDA）,activity of total antioxidant capacity（ TAC） and super oxide dismutase（ SOD） in frontal cortex were determined by Elisa.Disruption of blood-brain barrier（ BBB） was evaluated by Evans blue staining. Protein levels of occludin,claudin-5and Zo-1 in frontal cortex were measured by Western Blot. Results： Treatment with Tempol significantly delayed the episode of stroke（ 36 d vs 20 d,P〈0. 05）,reduced the incidence of stroke（ 75% vs 100%,P〈0. 05）,and increased the survival ratio（ 45% vs 25%,P〈0. 05） in SHRSP rats. Levels of MDA in the frontal cortex were reduced in Tempol group than in vehicle group（ 0. 63 ± 0. 04 nmol / mg vs 1. 23 ± 0. 07 nmol / mg,P〈0. 05）. Both the activity of TAC and SOD in the frontal cortex was enhanced by administration of Tempol（ 25. 6 ± 3. 4 U / mg vs 15. 6 ± 1. 2 U / mg,P〈0. 05; 7. 46 ± 0. 92 U / mg vs 5. 2 ± 0. 7 U / mg,P〈0. 05）. Furthermore,the levels of Evans blue in the frontal cortex were decreased（ 3. 75 ± 0. 42 μg / mg vs 6. 16 ± 0. 34 μg / mg,P〈0. 05）,and protein levels of occludin,claudin-5,and Zo-1 in the frontal cortex were increased in Tempol group. Conclusion： Tempol shows beneficial effects in loweringthe risk of stroke in cerebral small vessel disease by reducing oxidative stress and ameliorating the disruption of BBB in the brain of rats.

关 键 词：TEMPOL 脑小血管病变 SHRSP 血脑屏障 氧化应激 大鼠 

分 类 号：R544.1[医药卫生—心血管疾病] R-332[医药卫生—内科学] R743.3[医药卫生—临床医学]