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罗沙司他药物延迟对大鼠多区域穿支皮瓣存活的影响。

Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats.

作者信息

Tao Xianyao, Pan Xiaoyun, Rui Yongjun, Xue Mingyu

机构信息

Department of Hand Surgery, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi 214000, Jiangsu, China.

出版信息

Open Med (Wars). 2023 Jul 31;18(1):20230762. doi: 10.1515/med-2023-0762. eCollection 2023.

DOI:10.1515/med-2023-0762
PMID:37554150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10404892/
Abstract

Roxadustat (FG-4592) is a specific hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor. We investigated the effects of FG-4592 pretreatment on survival and second choke vessels of multi-territory perforator flaps in rats. In total, 72 rats were divided into two groups ( = 36 each): the experimental (FG-4592) group and the control group. FG-4592 was administered orally as a single dose of 60 mg/kg every other day; the first drug solution was administered to the animals 7 days before the surgical procedure. On postoperative day 7, the surviving flap area was calculated. At 12 h post-surgery, in the second choke zone in the flaps, macrovascular hinges were compared by angiography and imaging, and microvascular changes were assessed by histology. Laser Doppler imaging was used to evaluate flap perfusion at the second choke zone at 12 h and 7 days after surgery. At 7 days after surgery, the flap survival area and perfusion were significantly greater in rats given FG-4592 compared with controls. At 12 h after surgery, the diameter of macrovascular and microvascular vessels, nitric oxide content, perfusion, and the protein levels of HIF-1α and inducible nitric oxide synthase were also significantly greater in FG-4592-treated rats than controls. In conclusion, pretreatment with roxadustat may improve initial flap survival and dilate the second choke zone vessels in a multi-territory perforator flap.

摘要

罗沙司他(FG-4592)是一种特异性缺氧诱导因子(HIF)脯氨酰羟化酶抑制剂。我们研究了FG-4592预处理对大鼠多区域穿支皮瓣存活及二次阻断血管的影响。总共72只大鼠被分为两组(每组 = 36只):实验组(FG-4592)和对照组。每隔一天口服给予FG-4592,单次剂量为60 mg/kg;在手术前7天给动物施用首次药物溶液。术后第7天,计算存活皮瓣面积。在手术后12小时,通过血管造影和成像比较皮瓣二次阻断区域的大血管绞链,并通过组织学评估微血管变化。使用激光多普勒成像在手术后12小时和7天评估皮瓣二次阻断区域的灌注情况。与对照组相比,给予FG-4592的大鼠在术后7天时皮瓣存活面积和灌注明显更大。在手术后12小时,FG-4592处理的大鼠的大血管和微血管直径、一氧化氮含量、灌注以及HIF-1α和诱导型一氧化氮合酶的蛋白质水平也明显高于对照组。总之,罗沙司他预处理可能会提高多区域穿支皮瓣的初始皮瓣存活率,并扩张二次阻断区域的血管。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/6f7ddb59bf40/j_med-2023-0762-fig007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/a355d71f8d77/j_med-2023-0762-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/37f694cde008/j_med-2023-0762-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/77c03fdb738e/j_med-2023-0762-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/d64df30e9907/j_med-2023-0762-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/386276905419/j_med-2023-0762-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/2b94ed1f00cd/j_med-2023-0762-fig006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/6f7ddb59bf40/j_med-2023-0762-fig007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/a355d71f8d77/j_med-2023-0762-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/37f694cde008/j_med-2023-0762-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/77c03fdb738e/j_med-2023-0762-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/d64df30e9907/j_med-2023-0762-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/386276905419/j_med-2023-0762-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/2b94ed1f00cd/j_med-2023-0762-fig006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dcd/10404892/6f7ddb59bf40/j_med-2023-0762-fig007.jpg

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J Reconstr Microsurg. 2016 Nov;32(9):643-649. doi: 10.1055/s-0036-1584808. Epub 2016 Jul 1.
2
Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.罗沙司他(FG-4592)治疗维持性血液透析患者贫血的 2 期随机、6-19 周、开放标签、活性对照、剂量范围、安全性和探索性疗效研究:与促红细胞生成素α的比较
Am J Kidney Dis. 2016 Jun;67(6):912-24. doi: 10.1053/j.ajkd.2015.12.020. Epub 2016 Feb 2.
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Experimental study of survival of pedicled perforator flap with flow-through and flow-end blood supply.
带穿支血管蒂的动静脉血流通过与终末血流供养皮瓣的成活率的实验研究。
Br J Surg. 2015 Mar;102(4):375-81. doi: 10.1002/bjs.9732.
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Role of the NO/cGMP pathway in postoperative vasodilation in perforator flaps.一氧化氮/环磷酸鸟苷途径在穿支皮瓣术后血管舒张中的作用。
J Reconstr Microsurg. 2015 Feb;31(2):107-12. doi: 10.1055/s-0034-1384663. Epub 2015 Jan 20.
5
True and 'choke' anastomoses between perforator angiosomes: part II. dynamic thermographic identification.穿支血管供血区的真吻合和“绞锁”吻合:第二部分。动态热成像鉴定。
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