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帕瑞昔布通过抑制炎症反应和基质金属蛋白酶的产生来改善动脉粥样硬化斑块的稳定性。

Parecoxib improves atherosclerotic plaque stability by suppressing inflammation and inhibiting matrix metalloproteinases production.

机构信息

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Department of Cardiology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

出版信息

Biomed Pharmacother. 2021 Jun;138:111423. doi: 10.1016/j.biopha.2021.111423. Epub 2021 Mar 16.

DOI:10.1016/j.biopha.2021.111423
PMID:33740522
Abstract

With the aging population, coronary syndrome is one of the leading causes of mortality. Atherosclerosis is the pathophysiological basis of coronary syndrome, which is caused by plaque rupture and predisposed or aggravated by many perioperative complications. Parecoxib is one of the most widely used nonsteroidal anti-inflammatory perioperative drugs. This study aims to evaluate the potential benefits of parecoxib on atherosclerosis progression. Apolipoprotein E-deficient (Apo E-/-) mice were intraperitoneally injected by parecoxib (par group) or saline (control group) and, meanwhile, were given a western diet for 12 weeks. The aorta and aortic root were examined by oil red O (ORO) staining for atherosclerotic lesions. The expression level of matrix metalloproteinases (MMPs), was investigated using immunofluorescence and western blot. Macrophage inflammation was investigated by Q-PCR. Parecoxib treatment increased the number of vascular smooth muscle cells (VSMC) and amount of collagen, while and decreased the number of macrophages in murine aortic walls. The expression of MMP1, 2, 9, and 13 as well as IL- 1β and IL-6 were also decreased in the par group. However, there was no statistical difference in lipid infiltration between the two groups. Parecoxib could improve plaque stability by suppressing inflammation and inhibiting MMPs production.

摘要

随着人口老龄化,冠状动脉综合征是导致死亡的主要原因之一。动脉粥样硬化是冠状动脉综合征的病理生理学基础,它是由斑块破裂引起的,并由许多围手术期并发症引起或加重。帕瑞昔布是围手术期最广泛使用的非甾体类抗炎药之一。本研究旨在评估帕瑞昔布对动脉粥样硬化进展的潜在益处。载脂蛋白 E 缺陷(Apo E-/-)小鼠经腹腔注射帕瑞昔布(帕组)或生理盐水(对照组),同时给予西方饮食 12 周。用油红 O(ORO)染色法检测主动脉和主动脉根部的动脉粥样硬化病变。用免疫荧光和 Western blot 检测基质金属蛋白酶(MMPs)的表达水平。用 Q-PCR 检测巨噬细胞炎症。帕瑞昔布治疗增加了血管平滑肌细胞(VSMC)的数量和胶原的含量,同时减少了小鼠主动脉壁中巨噬细胞的数量。MMP1、2、9 和 13 的表达以及 IL-1β 和 IL-6 也在帕组中降低。然而,两组之间的脂质浸润没有统计学差异。帕瑞昔布通过抑制炎症和抑制 MMPs 的产生来改善斑块稳定性。

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