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大鼠皮瓣模型中缺血再灌注损伤的预防:肥大细胞、色甘酸钠及组胺受体阻断的作用

Prevention of ischemia-reperfusion injury in a rat skin flap model: the role of mast cells, cromolyn sodium, and histamine receptor blockade.

作者信息

Cordeiro P G, Lee J J, Mastorakos D, Hu Q Y, Pinto J T, Santamaria E

机构信息

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

出版信息

Plast Reconstr Surg. 2000 Feb;105(2):654-9. doi: 10.1097/00006534-200002000-00026.

DOI:10.1097/00006534-200002000-00026
PMID:10697173
Abstract

The objective of this study was to examine the role of mast cells and their principal product, histamine, in ischemia/reperfusion injury. Cromolyn sodium, diphenhydramine, and cimetidine were administered to ischemic flaps just before reperfusion and evaluated for flap survival, mast cell count, neutrophil count, and myeloperoxidase levels. Epigastric island skin flaps were elevated in 49 rats; they were rendered ischemic by clamping the artery for 10 hours. Thirty minutes before reperfusion, the rats were treated with intraperitoneal saline (n = 11), cimetidine (n = 11), diphenhydramine (n = 11), or cromolyn sodium (n = 10). Flap survival was evaluated at 7 days. Neutrophil counts, mast cell counts, and myeloperoxidase levels were evaluated 12 hours after reperfusion. Flap necrosis in the sham group of animals (n = 6) was 0.0 percent, as expected, whereas the control group (saline-treated animals) had 47.3+/-33.4 percent necrosis. Animals treated with diphenhydramine and cimetidine demonstrated a significant decrease in flap necrosis to 17.7+/-8.8 percent and 19.4+/-14.7 percent, respectively. This protective effect was not seen with cromolyn sodium (44.3+/-35.6 percent). Both neutrophil and mast cell counts were significantly decreased in flaps from antihistamine-treated and sham animals versus both saline- and cromolyn sodium-treated groups. The administration of diphenhydramine and cimetidine before reperfusion can significantly reduce the extent of flap necrosis and the neutrophil and mast cell counts caused by ischemia/reperfusion. This protective effect is not seen with cromolyn sodium. The protective effect of antihistamines on flap necrosis might be related to the decrease in neutrophils and, possibly, mast cells within the flap.

摘要

本研究的目的是探讨肥大细胞及其主要产物组胺在缺血/再灌注损伤中的作用。在再灌注前,将色甘酸钠、苯海拉明和西咪替丁给予缺血皮瓣,并评估皮瓣存活率、肥大细胞计数、中性粒细胞计数和髓过氧化物酶水平。在49只大鼠中掀起上腹部岛状皮瓣;通过夹闭动脉10小时使其缺血。在再灌注前30分钟,给大鼠腹腔注射生理盐水(n = 11)、西咪替丁(n = 11)、苯海拉明(n = 11)或色甘酸钠(n = 10)。在7天时评估皮瓣存活率。在再灌注12小时后评估中性粒细胞计数、肥大细胞计数和髓过氧化物酶水平。如预期的那样,假手术组动物(n = 6)的皮瓣坏死率为0.0%,而对照组(生理盐水处理的动物)的坏死率为47.3±33.4%。用苯海拉明和西咪替丁治疗的动物皮瓣坏死率显著降低,分别降至17.7±8.8%和19.4±14.7%。色甘酸钠未观察到这种保护作用(44.3±35.6%)。与生理盐水和色甘酸钠处理组相比,抗组胺药处理组和假手术组动物皮瓣中的中性粒细胞和肥大细胞计数均显著降低。再灌注前给予苯海拉明和西咪替丁可显著降低缺血/再灌注引起的皮瓣坏死程度以及中性粒细胞和肥大细胞计数。色甘酸钠未观察到这种保护作用。抗组胺药对皮瓣坏死的保护作用可能与皮瓣内中性粒细胞以及可能还有肥大细胞数量的减少有关。

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引用本文的文献

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Front Pharmacol. 2020 Jan 22;10:1605. doi: 10.3389/fphar.2019.01605. eCollection 2019.
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Ischaemic Preconditioning Suppresses Necrosis of Adipocutaneous Flaps in a Diabetic Rat Model Regardless of the Manner of Preischaemia Induction.无论缺血预适应的诱导方式如何,缺血预适应均可抑制糖尿病大鼠模型中皮瓣的坏死。
Dermatol Res Pract. 2017;2017:4137597. doi: 10.1155/2017/4137597. Epub 2017 Oct 18.
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Stress induces more serious barrier dysfunction in follicle-associated epithelium than villus epithelium involving mast cells and protease-activated receptor-2.
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Sci Rep. 2017 Jul 10;7(1):4950. doi: 10.1038/s41598-017-05064-y.
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