R(+)-普拉克索对大鼠短暂性局灶性脑缺血损伤的神经保护作用

doi:10.3969/j.issn.1006-7795.2014.02.017

首都医科大学学报 ›› 2014, Vol. 35 ›› Issue (2): 225-230.doi: 10.3969/j.issn.1006-7795.2014.02.017

R(+)-普拉克索对大鼠短暂性局灶性脑缺血损伤的神经保护作用

尹洁, 闫峰, 罗玉敏, 李森, 刘克建, 赵咏梅

首都医科大学宣武医院北京市老年病医疗研究中心神经变性病教育部重点实验室脑血管病转化医学北京市重点实验室, 北京 100053

收稿日期:2014-01-13 出版日期:2014-04-21 发布日期:2014-04-16
基金资助:
国家自然科学基金（81171242），北京市自然科学基金（7122036），脑血管病转化医学北京市重点实验室开放课题（2013NXGZ03）资助。

Neuroprotective effect of R(+)-pramipexole on brain injury following transient focal cerebral ischemia in rats

Yin Jie, Yan Feng, Luo Yumin, Li Sen, Liu Kejian, Zhao Yongmei

Xuanwu Hospital, Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory of Neurodegenerative Diseases of Ministry of Education, Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing 100053, China

Received:2014-01-13 Online:2014-04-21 Published:2014-04-16
Contact: 赵咏梅 E-mail:yongmeizhao@hotmail.com
Supported by:
This study was supported by the National Natural Science Foundation of China(81171242), Natural Science Foundation of Beijing(7122036), Open Project of Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases(2013NXGZ03).

摘要/Abstract

摘要：

目的研究R（+）-普拉克索对短暂性局灶性脑缺血大鼠脑内活性氧自由基（reactive oxygen species，ROS）产生以及脑损伤的影响，探讨R（+）-PPX对脑缺血损伤的保护作用，寻找防治缺血性脑血管病的有效方法。方法采用数字表法随机将30只健康雄性SD大鼠分为：假手术组（Sham组，n=10）；大脑中动脉梗死组（MCAO组，n=10）；MCAO+R（+）-PPX组。使用线栓法制作大鼠缺血90 min再灌注模型，术中监测大鼠心率、平均动脉压及肛温，使其保持在正常范围。每组分别于脑缺血再灌注后6、24 h取脑组织行TTC染色检测大鼠脑梗死体积，并制作脑组织冰冻切片，采用H2DCF-DA染色法计数半暗带区ROS阳性细胞数目并检测其平均荧光强度。结果 1）在MCAO手术过程中，Sham组、MCAO组和MCAO+R（+）-PPX组大鼠的心率、平均动脉压及肛温差异均无统计学意义。2）Sham组大鼠无脑梗死发生。缺血再灌注6 h及24 h，MCAO组、MCAO+R（+）-PPX组大鼠脑梗死体积均比Sham组显著增加（P<0.05）且随再灌注时间延长递增（P<0.05）。再灌注6 h时，MCAO+R（+）-PPX组与MCAO组相比，脑梗死体积明显减少，差异有统计学意义（P<0.05），而再灌注24 h时，MCAO+R（+）-PPX组脑梗死体积与MCAO组相比差异无统计学意义（P > 0.05）。3）Sham组大鼠脑内无缺血半暗带区。缺血再灌注6 h及24 h，MCAO组、MCAO+R（+）-PPX组大鼠脑缺血半暗带区域H2DCF-DA阳性染色细胞数目及平均荧光强度均随再灌注时间延长递增（P<0.05）。再灌注6 h时，与MCAO组相比，MCAO+R（+）-PPX组的H2DCF-DA阳性染色细胞数目及平均荧光强度明显减少，差异有统计学意义（P<0.05）。而再灌注24 h时，MCAO+R（+）-PPX组大鼠H2DCF-DA阳性染色细胞数目及平均荧光强度与MCAO组相比差异无统计学意义（P>0.05）。结论一次性给予R（+）-PPX可在缺血再灌注早期（6 h）明显减少MCAO大鼠脑内的ROS生成，减少脑梗死体积。R（+）-PPX防治脑缺血损伤的作用值得深入研究。

关键词: 脑缺血, 大脑中动脉梗死, 再灌注, R(+)-普拉克索, 大鼠

Abstract:

Objective To study the effect of R(+)-pramipexole on reactive oxygen species(ROS) production and brain injury in transient focal ischemic rats and to investigate the neuroprotective effects of R(+)-PPX on cerebral ischemic injury and explore the preventive and therapeutic methods for ischemic cerebrovascular disease. Methods Thirty male Sprague Dawley rats were divided randomly into three groups: Sham group(n=10), middle cerebral artery occlusion group(MCAO, n=10) and MCAO+ R(+)-PPX group. MCAO operation was performed by using suture method. The rats underwent right MCAO for 90 min. The heart rate, mean arterial blood pressure(MABP) and rectal temperature were monitored to keep in normal range during the operation. At 6 h or 24 h after reperfusion, brains were removed and dyed with 2, 3, 5-triphenyltetrazolium chloride to measure the infarct volume. H2DCF-DA was used to detect ROS in the penumbra of the brain. Results 1) There was no statistical difference in heart rates, MABP and rectal temperature among sham, MCAO and MCAO+R(+)-PPX group rats. 2) No infarction was observed in the brain of sham group rats whereas the brain infarct volume in both MCAO group and MCAO+ R(+)-PPX group increased significantly at 6 h to 24 h after reperfusion(P<0.05). The infarct volume of both MCAO group and MCAO+R(+)-PPX group showed time-dependent increasing tendency(P<0.05). At 6 h after reperfusion, the brain infarct volume in MCAO+R(+)-PPX group rats decreased significantly compared with that of MCAO group rats(P<0.05) while the brain infarct volume in MCAO+ R(+)-PPX group rats showed no statistical difference compared with that of MCAO group rats at 24 h after reperfusion(P>0.05). 3) No penumbra was observed in the brain of sham group rats. The number and fluorescence intensity of H2DCF-DA-positive cells in the penumbra of MCAO group and MCAO+R(+)-PPX group rats from 6 h to 24 h after reperfusion showed time-dependent increasing tendency(P<0.05). At 6 h after reperfusion, the number of H2DCF-DA-positive cells and fluorescence intensity in the penumbra of MCAO+R(+)-PPX group rats decreased significantly compared with that of MCAO group rats(P<0.05) while the number of H2DCF-DA-positive cells and fluorescence intensity in the penumbra of MCAO+R(+)-PPX group rats showed no statistical difference with that of MCAO group rats at 24 h after reperfusion(P>0.05). Conclusion A single administration of R(+)-PPX could decrease ROS production, reduce infarct volume in MCAO rats at early reperfusion time(6 h). The effect of R(+)-PPX on cerebral ischemic injury deserves further study.

Key words: cerebral ischemia, middle cerebral artery occlusion, reperfusion, R(+)-PPX, rats

中图分类号:

R743.31

尹洁, 闫峰, 罗玉敏, 李森, 刘克建, 赵咏梅. R(+)-普拉克索对大鼠短暂性局灶性脑缺血损伤的神经保护作用[J]. 首都医科大学学报, 2014, 35(2): 225-230.

Yin Jie, Yan Feng, Luo Yumin, Li Sen, Liu Kejian, Zhao Yongmei. Neuroprotective effect of R(+)-pramipexole on brain injury following transient focal cerebral ischemia in rats[J]. Journal of Capital Medical University, 2014, 35(2): 225-230.

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R(+)-普拉克索对大鼠短暂性局灶性脑缺血损伤的神经保护作用

Neuroprotective effect of R(+)-pramipexole on brain injury following transient focal cerebral ischemia in rats

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