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口服环丙沙星会影响成年和老年雄性白化大鼠的胸主动脉结构吗?氟喹诺酮类药物诱发主动脉夹层风险的线索。

Does oral ciprofloxacin affect the structure of thoracic aorta in adult and senile male albino rats? A clue to fluoroquinolones-induced risk of aortic dissection.

作者信息

Al-Neklawy Ahmed Farid, El-Nefiawy Nagwa Ebrahim, Rady Hagar Yousry

机构信息

Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Department of Physiological Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia.

出版信息

Anat Cell Biol. 2022 Mar 31;55(1):79-91. doi: 10.5115/acb.21.170.

DOI:10.5115/acb.21.170
PMID:35354674
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8968223/
Abstract

In this study, the effect of oral ciprofloxacin on the structure of the thoracic aorta in rats was investigated. Twenty four male albino rats were divided into 4 groups (6 rats/group): group I (adult control), group II (adult rats treated with ciprofloxacin), group III (senile control), and group IV (senile rats treated with ciprofloxacin). Rats in groups II and IV received ciprofloxacin via oral gavage in a daily dose of 3.5 mg/kg/d for 14 days, while control rats received equivalent amount of distilled water used to dissolve the drug. After 2 weeks, all rats were sacrificed, thoracic aortae were dissected, and half of the specimens were processed for paraffin sections and examined by light microscopy. The other half of the specimens were prepared for scanning electron microscopy. Sections from rats treated with ciprofloxacin showed evident damaging effect on aortic wall particularly in (group IV). Aortic intima showed, focal desquamation of the lining epithelium. Tunica media exhibited loss of the normal concentric arrangement and degeneration of the smooth muscle cells. Immune staining for alpha smooth muscle actin showed muscle damage. Interestingly, some sections in (group IV) showed out-pouch (aneurysm like) of the aortic wall. There was dense collagen fibers deposition. Scanning electron microscopic observations of (group IV) revealed uneven intima, adherent blood cells and fibrin filaments to damaged intima, and out-pouch formation. It was concluded that oral ciprofloxacin caused deleterious structural changes in the thoracic aortic wall of rats explaining clinical observations of fluoroquinolones induced risk of aortic dissection and aneurysm.

摘要

在本研究中,调查了口服环丙沙星对大鼠胸主动脉结构的影响。将24只雄性白化大鼠分为4组(每组6只大鼠):第一组(成年对照组)、第二组(用环丙沙星治疗的成年大鼠)、第三组(老年对照组)和第四组(用环丙沙星治疗的老年大鼠)。第二组和第四组的大鼠通过口服灌胃给予环丙沙星,每日剂量为3.5mg/kg/d,持续14天,而对照大鼠给予等量用于溶解药物的蒸馏水。2周后,处死所有大鼠,解剖胸主动脉,将一半标本制成石蜡切片并进行光学显微镜检查。另一半标本用于扫描电子显微镜检查。用环丙沙星治疗的大鼠的切片显示对主动脉壁有明显的损伤作用,特别是在第四组。主动脉内膜显示内衬上皮细胞局灶性剥脱。中膜表现为正常同心排列丧失和平滑肌细胞变性。α平滑肌肌动蛋白的免疫染色显示肌肉损伤。有趣的是,第四组的一些切片显示主动脉壁有向外膨出(类似动脉瘤)。有致密的胶原纤维沉积。第四组的扫描电子显微镜观察显示内膜不均匀、受损内膜上有黏附的血细胞和纤维蛋白丝以及向外膨出形成。得出的结论是,口服环丙沙星导致大鼠胸主动脉壁出现有害的结构变化,这解释了氟喹诺酮类药物引起主动脉夹层和动脉瘤风险的临床观察结果。

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本文引用的文献

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PeerJ. 2021 Aug 30;9:e12003. doi: 10.7717/peerj.12003. eCollection 2021.
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The estimation of age from elastic fibers in the tunica media of the aortic wall in a thai population: a preliminary study using aorta image analysis.泰国人群中通过主动脉壁中膜弹性纤维估计年龄:一项使用主动脉图像分析的初步研究
Anat Cell Biol. 2020 Sep 30;53(3):284-291. doi: 10.5115/acb.20.094.
3
Fluoroquinolones and Aortic Diseases: Is There a Connection.
氟喹诺酮类药物与主动脉疾病:存在关联吗?
Aorta (Stamford). 2019 Apr;7(2):35-41. doi: 10.1055/s-0039-1693468. Epub 2019 Sep 17.
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Oral Fluoroquinolones and Risk of Mitral and Aortic Regurgitation.口服氟喹诺酮类药物与二尖瓣和主动脉瓣反流的风险。
J Am Coll Cardiol. 2019 Sep 17;74(11):1444-1450. doi: 10.1016/j.jacc.2019.07.035.
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Effect of Ciprofloxacin on Susceptibility to Aortic Dissection and Rupture in Mice.环丙沙星对小鼠主动脉夹层和破裂易感性的影响。
JAMA Surg. 2018 Sep 1;153(9):e181804. doi: 10.1001/jamasurg.2018.1804. Epub 2018 Sep 19.
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