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选择性环氧化酶-2 抑制剂对大鼠随意皮瓣存活的不良影响。

The adverse effect of selective cyclooxygenase-2 inhibitor on random skin flap survival in rats.

机构信息

Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, The Second Clinical Medical College of Wenzhou Medical College, Wenzhou, China.

出版信息

PLoS One. 2013 Dec 6;8(12):e82802. doi: 10.1371/journal.pone.0082802. eCollection 2013.

DOI:10.1371/journal.pone.0082802
PMID:24324831
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3855778/
Abstract

BACKGROUND

Cyclooxygenase-2(COX-2) inhibitors provide desired analgesic effects after injury or surgery, but evidences suggested they also attenuate wound healing. The study is to investigate the effect of COX-2 inhibitor on random skin flap survival.

METHODS

The McFarlane flap model was established in 40 rats and evaluated within two groups, each group gave the same volume of Parecoxib and saline injection for 7 days. The necrotic area of the flap was measured, the specimens of the flap were stained with haematoxylin-eosin(HE) for histologic analysis. Immunohistochemical staining was performed to analyse the level of VEGF and COX-2 .

RESULTS

7 days after operation, the flap necrotic area ratio in study group (66.65 ± 2.81)% was significantly enlarged than that of the control group(48.81 ± 2.33)%(P <0.01). Histological analysis demonstrated angiogenesis with mean vessel density per mm(2) being lower in study group (15.4 ± 4.4) than in control group (27.2 ± 4.1) (P <0.05). To evaluate the expression of COX-2 and VEGF protein in the intermediate area II in the two groups by immunohistochemistry test .The expression of COX-2 in study group was (1022.45 ± 153.1), and in control group was (2638.05 ± 132.2) (P <0.01). The expression of VEGF in the study and control groups were (2779.45 ± 472.0) vs (4938.05 ± 123.6)(P <0.01).In the COX-2 inhibitor group, the expressions of COX-2 and VEGF protein were remarkably down-regulated as compared with the control group.

CONCLUSION

Selective COX-2 inhibitor had adverse effect on random skin flap survival. Suppression of neovascularization induced by low level of VEGF was supposed to be the biological mechanism.

摘要

背景

环氧化酶-2(COX-2)抑制剂在损伤或手术后提供了所需的镇痛效果,但有证据表明它们也会减弱伤口愈合。本研究旨在探讨 COX-2 抑制剂对随意皮瓣存活的影响。

方法

在 40 只大鼠中建立了 McFarlane 皮瓣模型,并将其分为两组进行评估,每组给予相同体积的帕瑞昔布钠和生理盐水注射 7 天。测量皮瓣的坏死面积,对皮瓣标本进行苏木精-伊红(HE)染色进行组织学分析。进行免疫组织化学染色分析血管内皮生长因子(VEGF)和 COX-2 的水平。

结果

术后 7 天,研究组(66.65±2.81)%的皮瓣坏死面积比明显大于对照组(48.81±2.33)%(P<0.01)。组织学分析表明,研究组的平均血管密度为每平方毫米 15.4±4.4,明显低于对照组的 27.2±4.1(P<0.05)。通过免疫组织化学试验评估两组中间区 II 中 COX-2 和 VEGF 蛋白的表达。研究组 COX-2 的表达为(1022.45±153.1),对照组为(2638.05±132.2)(P<0.01)。研究组和对照组的 VEGF 表达分别为(2779.45±472.0)与(4938.05±123.6)(P<0.01)。在 COX-2 抑制剂组中,与对照组相比,COX-2 和 VEGF 蛋白的表达明显下调。

结论

选择性 COX-2 抑制剂对随意皮瓣存活有不良影响。低水平 VEGF 诱导的新生血管形成抑制可能是其生物学机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/0fece8c47ebf/pone.0082802.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/ce210094c98a/pone.0082802.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/7a60f8952116/pone.0082802.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/ac052c593768/pone.0082802.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/f4d1a7f05cca/pone.0082802.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/0fece8c47ebf/pone.0082802.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/ce210094c98a/pone.0082802.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/7a60f8952116/pone.0082802.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/ac052c593768/pone.0082802.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/f4d1a7f05cca/pone.0082802.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea1/3855778/0fece8c47ebf/pone.0082802.g005.jpg

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