盐酸法舒地尔对蛛网膜下腔出血大鼠学习记忆功能及海马CA1区自噬的影响

doi:10.3969/j.issn.1006-9771.2017.03.003

《中国康复理论与实践》 ›› 2017, Vol. 23 ›› Issue (3): 257-262.doi: 10.3969/j.issn.1006-9771.2017.03.003

盐酸法舒地尔对蛛网膜下腔出血大鼠学习记忆功能及海马CA1区自噬的影响

孙林林¹, 刘振刚¹, 张志勇², 陈扬², 刘俊杰¹, 付爱军², 李建民²

[摘要] 目的研究盐酸法舒地尔对蛛网膜下腔出血(SAH)大鼠学习记忆及海马CA1区自噬的影响。方法雄性Sprague-Dawley大鼠54只,随机分为假手术组、SAH组、药物组,各18只。颈内动脉刺破法造模,药物组造模成功后予盐酸法舒地尔10 mg/kg腹腔注射,每天1次,假手术组和SAH组腹腔注射等量生理盐水,干预后6 h、24 h、72 h予穿梭箱试验;取海马CA1区组织HE染色观察细胞形态,免疫组织化学染色观察Beclin-1和微管相关蛋白l轻链3-Ⅱ(LC3-Ⅱ)的表达。结果与假手术组相比,SAH组大鼠各时间点穿梭箱试验逃避反应次数减少(P<; 0.05),逃避反应时间延长(P<; 0.05);海马CA1区神经细胞数目减少(P<; 0.05),Beclin-1、LC3-Ⅱ表达增高(P<; 0.05)。与SAH组相比,药物组各时间点逃避反应次数增多(P<; 0.05),逃避反应时间减少(P<; 0.05);海马CA1区神经细胞增多(P<; 0.05),Beclin-1、LC3-Ⅱ表达进一步增多(P<; 0.05)。结论盐酸法舒地尔可改善SAH大鼠学习记忆功能,减少神经细胞损伤,增强海马CA1区自噬。

收稿日期:2016-12-11 出版日期:2017-03-05 发布日期:2017-03-31
作者简介:孙林林(1989-),男,汉族,河南商丘市人,硕士研究生,医师,主要研究方向：脑血管病。通讯作者：付爱军,男,硕士,主任医师,主要研究方向：脑血管病。E-mail: tsfaj@sina.com。
基金资助:
河北省重大医学课题(No.ZD2013093)

Effects of Fasudil Hydrochloride on Learning and Memory Ability and Autophagy in CA1 Area of Hippocampus in Subarachnoid Hemorrhage Rats

SUN Lin-lin¹, LIU Zhen-gang¹, ZHANG Zhi-yong², CHEN Yang², LIU Jun-jie¹, FU Ai-jun², LI Jian-min²

1. North China University of Science and Technology, Tangshan, Hebei 063000, China;
2. Department of Neurosurgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, China

Received:2016-12-11 Published:2017-03-05 Online:2017-03-31
Contact: Correspondence to FU Ai-jun. E-mail: tsfaj@sina.com

摘要/Abstract

摘要： 目的　研究盐酸法舒地尔对蛛网膜下腔出血(SAH)大鼠学习记忆及海马CA1区自噬的影响。方法　雄性Sprague-Dawley大鼠54只，随机分为假手术组、SAH组、药物组，各18只。颈内动脉刺破法造模，药物组造模成功后予盐酸法舒地尔10 mg/kg腹腔注射，每天1次，假手术组和SAH组腹腔注射等量生理盐水，干预后6 h、24 h、72 h予穿梭箱试验；取海马CA1区组织HE染色观察细胞形态，免疫组织化学染色观察Beclin-1和微管相关蛋白l轻链3-Ⅱ(LC3-Ⅱ)的表达。结果　与假手术组相比，SAH组大鼠各时间点穿梭箱试验逃避反应次数减少(P<0.05)，逃避反应时间延长(P<0.05)；海马CA1区神经细胞数目减少(P<0.05)，Beclin-1、LC3-Ⅱ表达增高(P<0.05)。与SAH组相比，药物组各时间点逃避反应次数增多(P<0.05)，逃避反应时间减少(P<0.05)；海马CA1区神经细胞增多(P<0.05)，Beclin-1、LC3-Ⅱ表达进一步增多(P<0.05)。结论　盐酸法舒地尔可改善SAH大鼠学习记忆功能，减少神经细胞损伤，增强海马CA1区自噬。

关键词: 蛛网膜下腔出血, 盐酸法舒地尔, 学习记忆, 自噬, 大鼠

Abstract: ObjectiveTo investigate the effects of fasudil hydrochloride on learning and memory, and the autophagy in hippocampal CA1 neurons in subarachnoid hemorrhage (SAH) rats. MethodsFifty-four male Sprague-Dawley rats were randomly divided into sham group (n=18), SAH group (n=18) and drug group (n=18). Subarachnoid hemorrhage model was established with internal carotid artery puncture. The drug group was injected fasudil hydrochloride 10 mg/kg intraperitoneally after modeling per 24 hours, while the sham group and SAH group were injected the same volume of saline. They were tested with shuttle box test 6, 24 and 72 hours after intervention, then the hippocampal CA1 area was stained with HE and immunohistochemistry to observe the morphology of cells and the expression of Beclin-1 and microtubule-associated protein 1 light chain 3 II (LC3-II). ResultsCompared with the sham group, the frequence of avoidance decreased in SAH group at each time point (P<0.05), while the avoidance reaction time increased (P<0.05); the survival of neurons in hippocampal CA1 area decreased (P<0.05), and the expression of Beclin-1 and LC3-II increased (P<0.05). Compared with SAH group, the frequence of avoidance increased in the drug group at each time point (P<0.05), while the avoidance reaction time decreased (P<0.05); the survival of neurons in hippocampal CA1 area increased (P<0.05) and the expression of Beclin-1 and LC3-II increased further (P<0.05). ConclusionFasudil hydrochloride can improve learning and memory ability and protect neurons from damage, which may associate with the excess of autophagy activation in hippocampal CA1 areas in SAH rats.

Key words: subarachnoid hemorrhage, fasudil hydrochloride, learning and memory, autophagy, rats

中图分类号:

R743.35

孙林林, 刘振刚, 张志勇, 陈扬, 刘俊杰, 付爱军, 李建民. 盐酸法舒地尔对蛛网膜下腔出血大鼠学习记忆功能及海马CA1区自噬的影响[J]. 《中国康复理论与实践》, 2017, 23(3): 257-262.

SUN Lin-lin, LIU Zhen-gang, ZHANG Zhi-yong, CHEN Yang, LIU Jun-jie, FU Ai-jun, LI Jian-min. Effects of Fasudil Hydrochloride on Learning and Memory Ability and Autophagy in CA1 Area of Hippocampus in Subarachnoid Hemorrhage Rats[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2017, 23(3): 257-262.

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盐酸法舒地尔对蛛网膜下腔出血大鼠学习记忆功能及海马CA1区自噬的影响

Effects of Fasudil Hydrochloride on Learning and Memory Ability and Autophagy in CA1 Area of Hippocampus in Subarachnoid Hemorrhage Rats

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