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Rho激酶抑制剂对大鼠慢性脑灌注不足所致认知障碍的疗效

Efficacy of Rho kinase inhibitor on cognitive impairment induced by chronic cerebral hypoperfusion in rats.

作者信息

Zhang Qiang, Zhang Jun-Jian, Han Zhong-Mou

机构信息

Department of Neurology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.

Department of Neurology, Three Gorges University First Clinical Medical College Yichang 443000, China.

出版信息

Int J Clin Exp Med. 2015 Feb 15;8(2):2435-40. eCollection 2015.

PMID:25932185
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4402832/
Abstract

This work aims to explore the efficacy of Rho kinase inhibitor Fasudil on cognitive impairment induced by chronic cerebral hypoperfusion in rats. A total of 32 male adult Sprague Dawley (SD) rats were randomly divided into three groups: treatment group, control group and sham-operated group for severe carotid artery stenosis model. After two weeks, 8.35 mg/kg Fasudil and physiological saline were intraperitoneally applied twice per day in treatment group and control group, respectively. Morris water maze test was performed in each group to detect the changes of cognitive function and observe the hippocampal pathomorphology in rats after eight weeks. The average escape latency distinctly shortened (P < 0.01) and the percentage of swimming distance in the platform quadrant significantly increased (P < 0.01) in treatment group compared with those at corresponding time points in control group. The rate of carotid artery stenosis in rats had no statistical difference between treatment and control groups (P > 0.05). Fasudil effectively improved hippocampal pathomorphology. Rho kinase inhibitor obviously ameliorated cognitive impairment induced by chronic cerebral hypoperfusion in rats.

摘要

本研究旨在探讨Rho激酶抑制剂法舒地尔对大鼠慢性脑灌注不足所致认知功能障碍的疗效。将32只成年雄性Sprague Dawley(SD)大鼠随机分为三组:治疗组、对照组和重度颈动脉狭窄模型假手术组。两周后,治疗组和对照组分别每天腹腔注射8.35 mg/kg法舒地尔和生理盐水两次。八周后,对每组大鼠进行Morris水迷宫试验以检测认知功能变化,并观察大鼠海马的病理形态学。与对照组相应时间点相比,治疗组大鼠的平均逃避潜伏期明显缩短(P < 0.01),平台象限游泳距离百分比显著增加(P < 0.01)。治疗组与对照组大鼠的颈动脉狭窄率无统计学差异(P > 0.05)。法舒地尔有效改善了海马病理形态学。Rho激酶抑制剂明显改善了大鼠慢性脑灌注不足所致的认知功能障碍。

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本文引用的文献

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Carotid artery disease and cognitive impairment.颈动脉疾病与认知障碍。
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Carotid stenosis and the cognitive function.颈动脉狭窄与认知功能。
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Improvement of cognitive deficit and neuronal damage in rats with chronic cerebral ischemia via relative long-term inhibition of rho-kinase.通过相对长期抑制 Rho 激酶改善慢性脑缺血大鼠的认知缺陷和神经元损伤。
Cell Mol Neurobiol. 2008 Aug;28(5):757-68. doi: 10.1007/s10571-007-9157-x. Epub 2007 Jun 7.
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Rho-kinase activation in endothelial cells contributes to expansion of infarction after focal cerebral ischemia.内皮细胞中的Rho激酶激活会导致局灶性脑缺血后梗死范围扩大。
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Bone marrow stromal cells of transgenic mice can improve the cognitive ability of an Alzheimer's disease rat model.转基因小鼠的骨髓基质细胞可改善阿尔茨海默病大鼠模型的认知能力。
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Protection filter-related events in extracranial carotid artery stenting: a single-center experience.颅外颈动脉支架置入术中与保护滤器相关的事件:单中心经验
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Wide therapeutic time window for fasudil neuroprotection against ischemia-induced delayed neuronal death in gerbils.法舒地尔对沙鼠缺血性迟发性神经元死亡具有神经保护作用,其治疗时间窗较宽。
Brain Res. 2007 Jan 12;1128(1):175-80. doi: 10.1016/j.brainres.2006.10.027. Epub 2006 Nov 22.
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