摘要
脑小血管疾病(CSVD)是指一类由脑小血管改变而引发的疾病,会引起多种情况,如认知功能障碍等。然而,目前对这些疾病尚无有效治疗。最近的研究表明,炎症与这种疾病相关联。环氧合酶-2(COX-2)是一种炎症介质;然而,COX-2抑制剂是否可以抑制CSVD的恶化仍然不明。本研究以脑卒中自发性高血压大鼠(SHRSP)作为CSVD的模型,以SD(SD)大鼠作为对照。用COX-2抑制剂celecoxib 或者 vehicle给药脑卒中自发性高血压大鼠。进行Morris水迷宫实验并观察脑小血管和脑组织中的血管形态和Ⅰ型胶原和纤维连接蛋白的表达。测试的结果表明,与SD大鼠相比,加厚的小血管壁使SHRSP鼠,Ⅰ型胶原和纤维连接蛋白的表达增加并使其认知功能受损。此外,celecoxib显著下调了I型胶原和纤连蛋白的表达,减少了血管壁厚度的增加并改善了认知功能障碍。我们的研究表明,该COX-2抑制剂可以作为为药理干预CSVD的有希望的候选药物。
关键词: 脑小血管病,认知障碍,胶原I,换氧化酶-2,纤连蛋白,高血压
Current Alzheimer Research
Title:A Cyclooxygenase-2 Inhibitor Reduces Vascular Wall Thickness and Ameliorates Cognitive Impairment in a Cerebral Small Vessel Diseases Rat Model
Volume: 12 Issue: 7
Author(s): Jie Tang, Weizhong Xiao, Qinghua Li, Qiuqiong Deng, Xinquan Chu, Yang Chen, Danhong Pan and Jianhui Fu
Affiliation:
关键词: 脑小血管病,认知障碍,胶原I,换氧化酶-2,纤连蛋白,高血压
摘要: Cerebral small vessel disease (CSVD) is a group of diseases that originate from changes in cerebral small vessels and that cause many conditions, such as cognitive impairment. However, there is no effective therapy for these diseases. Recent studies have suggested that inflammation is associated with this disease. Cyclooxygenase-2 (cox-2) is an inflammatory mediator; however, whether a cox-2 inhibitor could protect against the CSVD progression remains unknown. In the present study, stroke-prone spontaneously hypertensive rats (SHRsp) were used as a model of CSVD, and Sprague Dawley (SD) rats served as the control. SHRsp were treated with the cox-2 inhibitor celecoxib or vehicle. The Morris water maze test was performed, and vascular morphometry and the expression of collagen I and fibronectin were examined in cerebral small vessels and cerebral tissue. The results revealed that thickened small veesel walls, increased expression of collagen I and fibronectin and impaired cognitive function in SHRsp compared with SD rats. Additionally, celecoxib significantly down-regulated the expression of collagen I and fibronectin, attenuated the increase in vascular wall thickness and ameliorates the cognitive impairment. Our study indicated that this cox-2 inhibitor may serve as a promising candidate for the pharmacological intervention of CSVD.
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Jie Tang, Weizhong Xiao, Qinghua Li, Qiuqiong Deng, Xinquan Chu, Yang Chen, Danhong Pan and Jianhui Fu , A Cyclooxygenase-2 Inhibitor Reduces Vascular Wall Thickness and Ameliorates Cognitive Impairment in a Cerebral Small Vessel Diseases Rat Model, Current Alzheimer Research 2015; 12 (7) . https://dx.doi.org/10.2174/1567205012666150710104924
DOI https://dx.doi.org/10.2174/1567205012666150710104924 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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