替米沙坦对局灶性脑缺血再灌注大鼠c-fos表达和神经保护  

Study of telmisartan on the c-fos expression and neuroprotection on MCAO rats

作　　者：周曾[1] 夏峰[1] 李美英[1] 储照虎[2] 吴家幂[2] 胡成伍[3] 

机构地区：[1]安徽马鞍山市人民医院神经内科,马鞍山243000 [2]皖南医学院附属弋矶山医院神经内科,芜湖241001 [3]湖北潜江市中心医院神经内科,潜江433100

出　　处：《中国实用神经疾病杂志》2010年第13期1-4,共4页Chinese Journal of Practical Nervous Diseases

摘　　要：目的研究不同剂量血管紧张素Ⅰ受体拮抗剂替米沙坦对大鼠脑缺血再灌注的神经保护作用。方法 60只大鼠随机分为4组,假手术组、生理盐水对照组、小剂量替米沙坦治疗组2 mg/(kg.d)、大剂量替米沙坦治疗组10 mg/(kg.d)。通过线栓法制作大鼠大脑中动脉缺血再灌注模型(MCAO),记录神经功能缺损评分、监测血压、梗死面积、c-fos的表达。结果小剂量替米沙坦组平均动脉压较对照组适度下降,大剂量组则较为剧烈。小剂量替米沙坦组脑梗死体积小于对照组(P<0.05),而大剂量组与对照组相比变化不大(P>0.05)。各组大鼠神经功能随时间推移逐渐恢复,但各组恢复程度不同,治疗组较对照组神经功能恢复明显较好(P<0.05)。c-fos的表达随损伤好转逐渐降低,应用替米沙坦干预后c-fos表达较对照组减少,且小剂量替米沙坦组减少更明显。结论小剂量替米沙坦可以提供降低血压之外的神经保护作用,其机制可能为减少c-fos表达,抑制缺血损伤后神经凋亡。大剂量替米沙坦无明显神经保护作用。Objective To investigate the neuroprotective effect of AT1-R telmisartan in various doses, on reperfusion after focal cerebral ischemia in SD male rat. Methods Sixty rats were randomly divided into 4 groups, which were the sham group, the saline control group, the low-dose telmisartan group（2 mg · kg^-1 · d 1）, and the high-dose telmisartan group（10 mg · kg^-1 · d^-1）. The MCAO model rats were formed by occluding middle cerebral artery of rats with nylon thread. We scored neurological deficit with Garcia JH law, monitored blood pressure through non-invasive blood pressure measurement system, determined the reliability, measured infarct size with TTC and detected c-fos expression with immunohistochemical stai- ning. Results The mean arterial pressure of the low-dose telmisartan group moderately declined than that of the control group. The mean arterial pressure of the high-dose group declined more markedly. The infarction area of the low-dose telmisartan group was less than that of the control group （P〈0. 05）, while the high-dose group was to the control group（P〈0. 05）. Neurological function of rats in each group gradually restored, but the degree of each group was different. The recovery of neurological function in the telmisartan groups was significantly better than that in the control group. As the injury improved gradually, the expression of c-fos reduced. After the intervention of telmisartan, the expression of c-fos reduced as compared with the control group, and the low-dose of telmisartan group reduced more obviously. Conclusion It shows that low-dose telmisartan is able to produce the neuroprotective effect without reducing blood pressure, while the high-dose telmisartan can not produce above mentioned effect, The mechanism may be to reduce the c-fos expression and inhibit neuronal apoptosis after ischemic injury.

关 键 词：脑缺血再灌注 血管紧张素 AT1受体 替米沙坦 神经保护 

分 类 号：R-33[医药卫生]