普拉克索联合左旋多巴对全脑缺血再灌注损伤大鼠认知能力及线粒体功能的影响

doi:10.3969/j.issn.1006-9771.2023.05.007

《中国康复理论与实践》 ›› 2023, Vol. 29 ›› Issue (5): 533-540.doi: 10.3969/j.issn.1006-9771.2023.05.007

普拉克索联合左旋多巴对全脑缺血再灌注损伤大鼠认知能力及线粒体功能的影响

康晓宇¹, 刘丽旭¹^,²^,³(), 王文竹²^,³, 王云雷¹^,²

1.首都医科大学康复医学院，北京市 100068
2.中国康复研究中心北京博爱医院，北京市 100068
3.神经损伤与康复北京市重点实验室，北京市 100068

收稿日期:2023-02-13 修回日期:2023-03-13 出版日期:2023-05-25 发布日期:2023-06-19
通讯作者: 刘丽旭(1972-)，女，汉族，湖南邵阳市人，博士，主任医师、副教授，主要研究方向：神经康复。E-mail：liulixu2004@163.com
作者简介:康晓宇(1998-)，女，满族，辽宁鞍山市人，硕士研究生，主要研究方向：神经康复。
基金资助:
1.国家自然科学基金项目(82271427);2.中国康复研究中心科研课题(2021ZX-01)

Effects of pramipexole combined with levodopa on cognitive and mitochondrial function of rats after global cerebral ischemia-reperfusion injury

KANG Xiaoyu¹, LIU Lixu¹^,²^,³(), WANG Wenzhu²^,³, WANG Yunlei¹^,²

1. Capital Medical University School of Rehabilitation Medicine, Beijing 100068, China
2. Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing 100068, China
3. Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing 100068, China

Received:2023-02-13 Revised:2023-03-13 Published:2023-05-25 Online:2023-06-19
Contact: LIU Lixu, E-mail: liulixu2004@163.com
Supported by:
National Natural Science Foundation of China(82271427);China Rehabilitation Research Center Research Project(2021ZX-01)

摘要/Abstract

摘要：

目的探讨多巴胺受体激动剂普拉克索与左旋多巴联用对全脑缺血再灌注损伤大鼠情绪和认知功能，以及线粒体膜电位的影响。

方法 80只雄性Sprague-Dawley大鼠分为假手术组(n = 20)、模型组(n = 20)、普拉克索组(n = 20)和联合组(n = 20)。后3组采用Pulsinelli四血管阻断法制备大鼠全脑缺血再灌注损伤模型。普拉克索组每天予普拉克索0.5 mg/kg腹腔注射，联合组每天予普拉克索0.5 mg/kg和左旋多巴50 mg/kg腹腔注射，共14 d。造模后3 d、7 d和14 d每组取5只行旷场试验，造模后7 d和14 d每组取5只行Y迷宫试验，造模后3 d、7 d和14 d每组取5只检测线粒体膜电位，造模后14 d每组取5只行尼氏染色。

结果与模型组相比，7 d和14 d时，普拉克索组和联合组旷场试验穿格次数增加(P < 0.05)，总轨迹长度增加(P < 0.05)，平均速度增加(P < 0.05)，7 d时普拉克索组中心区停留时间延长(P < 0.05)；7 d和14 d时，普拉克索组和联合组Y迷宫试验自发交替分增加(P < 0.05)；7 d和14 d时普拉克索组和联合组线粒体膜电位增加(P < 0.05)，14 d时普拉克索组线粒体膜电位低于联合组(P < 0.05)；14 d时普拉克索组和联合组海马CA1区存活神经元数量增加(P < 0.05)。

结论单用普拉克索即可改善全脑缺血再灌注损伤大鼠的情绪和认知功能，联用左旋多巴后有助于线粒体膜电位恢复。

关键词: 全脑缺血再灌注损伤, 普拉克索, 左旋多巴, 线粒体膜电位, 情绪, 认知

Abstract:

Objective To investigate the effects of dopamine receptor agonist pramipexole and levodopa on emotion and cognition, and mitochondrial membrane potential of rats after global cerebral ischemia-reperfusion injury.

Methods A total of 80 male Sprague-Dawley rats were divided into sham group (n = 20), model group (n = 20), pramipexole group (n = 20) and combined group (n = 20). The latter three groups were used to prepare the model of global cerebral ischemia-reperfusion injury with Pulsinelli's four-vessel occlusion. The pramipexole group was intraperitoneally injected pramipexole 0.5 mg/kg once a day, while the combined group was injected levodopa 50 mg/kg and pramipexole 0.5 mg/kg, for 14 days. Five rats in each group were tested with open field test three, seven and 14 days after modeling; five were tested with Y-maze test seven and 14 days after modeling; five were detected mitochondrial membrane potential three, seven and 14 days after modeling; and five were observed under Nissl's staining14 days after modeling.

Results Compared with the model group, the number of entries into the central zone (P < 0.05), total distance travelled (P < 0.05) and average velocity (P < 0.05) in the open field test increased in the pramipexole and combined groups seven and 14 days after modeling, duration spent in the central zone increased in the pramipexole and combined groups seven days after modeling (P < 0.05); the rate of spontaneous alternation of Y-maze test increased in the pramipexole and combined groups 14 days after modeling (P < 0.05); mitochondrial membrane potential in hippocampus increased in the pramipexole and combined groups seven and 14 days after modeling (P < 0.05), and it was less in the pramipexole group than in the combined group 14 days after modeling (P < 0.05); and the number of surviving neurons in the hippocampal CA1 increased in the pramipexole and combined groups 14 days after modeling (P < 0.05).

Conclusion Pramipexole may improve emotion and cognition of rats after global cerebral ischemia-reperfusion injury, and it may be helpful for restoring mitochondrial membrane potential as combining with levodopa.

Key words: global cerebral ischemia-reperfusion injury, pramipexole, levodopa, mitochondrial membrane potential, emotion, cognition

中图分类号:

R747.9

康晓宇, 刘丽旭, 王文竹, 王云雷. 普拉克索联合左旋多巴对全脑缺血再灌注损伤大鼠认知能力及线粒体功能的影响[J]. 《中国康复理论与实践》, 2023, 29(5): 533-540.

KANG Xiaoyu, LIU Lixu, WANG Wenzhu, WANG Yunlei. Effects of pramipexole combined with levodopa on cognitive and mitochondrial function of rats after global cerebral ischemia-reperfusion injury[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2023, 29(5): 533-540.

图/表 8

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参考文献 43

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组别	n	3 d	7 d	14 d
假手术组	5	15.80±4.21	16.60±9.21	11.60±7.99
模型组	5	1.60±0.89^a	2.00±1.00^a	3.00±1.73^a
普拉克索组	5	5.60±2.61^a,b	6.20±2.17^a,b	9.20±4.44^b
联合组	5	4.80±2.28^a,b	6.00±4.64^b	9.80±6.98^b
χ²值		15.354	13.745	8.191
P值		0.002	0.003	0.042

组别	n	3 d	7 d	14 d
假手术组	5	36.13±17.43	24.08±8.24	22.07±4.36
模型组	5	7.54±4.52	2.99±1.70^a	4.11±1.49^a
普拉克索组	5	11.30±6.32	16.43±9.06^b	20.06±16.47
联合组	5	19.13±8.94	9.58±3.69^a	19.42±13.80
F值		7.251	9.854	2.839
P值		0.003	0.001	0.071

组别	n	3 d	7 d	14 d
假手术组	5	7513.9±691.1	5925.5±1057.1	5440.4±1116.3
模型组	5	2517.3±249.7^a	2311.7±407.6^a	2744.6±682.9^a
普拉克索组	5	3907.7±649.2^a,b	4231.6±539.3^a,b	5249.9±1322.5^b
联合组	5	3185.0±483.0^a	4259.0±823.1^a,b	4821.7±498.6^b
F值		83.164	19.379	8.293
P值		< 0.001	< 0.001	0.001

组别	n	3 d	7 d	14 d
假手术组	5	25.16±2.30	19.82±3.54	18.20±3.74
模型组	5	8.42±0.83^a	7.76±1.36^a	9.20±2.27^a
普拉克索组	5	13.08±2.16^a,b	14.16±1.79^a,b	17.60±4.43^b
联合组	5	10.68±1.61^a	14.24±2.76^a,b	16.16±1.67^b
F值		83.988	19.314	8.274
P值		< 0.001	< 0.001	0.002

组别	n	7 d	14 d
假手术组	5	80.66±5.10	80.83±4.95
模型组	5	44.25±11.69^a	52.83±5.51^a
普拉克索组	5	82.72±8.22^b	73.45±10.79^b
联合组	5	72.25±3.71^b	74.73±6.99^b
F值		25.771	13.492
P值		< 0.001	< 0.001

普拉克索联合左旋多巴对全脑缺血再灌注损伤大鼠认知能力及线粒体功能的影响

Effects of pramipexole combined with levodopa on cognitive and mitochondrial function of rats after global cerebral ischemia-reperfusion injury

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组别	n	3 d	7 d	14 d
假手术组	5	70.38±7.97	73.04±6.96	97.36±7.49
模型组	5	66.71±0.91	47.56±3.61^a	61.66±3.69^a
普拉克索组	5	69.67±5.65	72.66±1.47^b	71.45±1.19^a,b
联合组	5	70.71±18.87	74.33±6.39^b	81.15±4.12^a,b,c
F值		0.147	31.935	52.592
P值		0.930	< 0.001	< 0.001

组别	n	存活神经元数
假手术组	5	114.40±2.70
模型组	5	74.20±3.56^a
普拉克索组	5	107.20±3.11^a,b
联合组	5	103.80±3.56^a,b
F值		147.679
P值		< 0.001

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