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血管内皮生长因子在肠缺血/再灌注不同阶段的应用:它对氧化应激、炎症和端粒酶活性有什么影响?

Application of vascular endothelial growth factor at different phases of intestinal ischemia/reperfusion: What are its effects on oxidative stress, inflammation and telomerase activity?

机构信息

Department of Physiology, Faculty of Medicine, Gazi University, Ankara, Turkey.

Department of Physiology, Faculty of Medicine, Katip Celebi University, Izmir, Turkey.

出版信息

Adv Clin Exp Med. 2020 Dec;29(12):1417-1424. doi: 10.17219/acem/126297.

DOI:10.17219/acem/126297
PMID:33389832
Abstract

BACKGROUND

Intestinal ischemic reperfusion injury (IRI) represents a great challenge in clinical practice, with high morbidity and mortality. Vascular endothelial growth factor (VEGF), as a signal protein, contributes to vasculogenesis and angiogenesis.

OBJECTIVES

To evaluate the local effectiveness of VEGF following intestinal IRI and its relation with application time.

MATERIAL AND METHODS

Thirty Wistar albino rats were allocated to 5 groups and underwent laparotomy. The superior mesenteric arteries (SMA) were dissected in 4 groups, while the control group (Gr C) underwent a resection of small and large intestines. The VEGF group (Gr V) received VEGF following SMA dissection, with no further intervention, and the remaining 3 groups were subjected to ischemia for 90 min through occlusion of SMA and reperfusion for 4 h. Ischemic reperfusion group (Gr I/R) received no additional medication, while the remaining 2 groups received VEGF just before ischemia (Gr V+I/R) and during reperfusion (Gr I/R+V).

RESULTS

Both applications of VEGF caused decreases in plasma levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), intestinal malondialdehyde (MDA), oxidized glutathione, protein carbonyl levels, and increases in intestinal total glutathione and superoxide dismutase (SOD) levels. Telomerase activity, which disappeared for Gr I/R, was found to be elevated following both treatment groups. Similarly, the histopathological scores were found better for both treatment groups, but Gr V-I/R represented best outcomes.

CONCLUSIONS

The findings of our study revealed that VEGF, applied either before ischemia or during reperfusion, is effective on local damage following intestinal IRI. By interpreting the biochemical analysis and histopathological findings, we conclude either treatment option to be considered according to the reason of intestinal IRI.

摘要

背景

肠缺血再灌注损伤(IRI)是临床实践中的一大挑战,具有较高的发病率和死亡率。血管内皮生长因子(VEGF)作为一种信号蛋白,有助于血管生成和血管生成。

目的

评估肠 IRI 后 VEGF 的局部疗效及其与应用时间的关系。

材料和方法

将 30 只 Wistar 白化大鼠分为 5 组并进行剖腹手术。在 4 组中解剖肠系膜上动脉(SMA),而对照组(Gr C)行小肠和大肠切除术。VEGF 组(Gr V)在 SMA 解剖后接受 VEGF,无进一步干预,其余 3 组通过 SMA 闭塞缺血 90 分钟,再灌注 4 小时。缺血再灌注组(Gr I/R)未接受额外药物治疗,其余 2 组在缺血前(Gr V+I/R)和再灌注时(Gr I/R+V)给予 VEGF。

结果

VEGF 的两种应用均降低了血浆白细胞介素 6(IL-6)、肿瘤坏死因子-α(TNF-α)、肠丙二醛(MDA)、氧化谷胱甘肽、蛋白羰基水平,增加了肠总谷胱甘肽和超氧化物歧化酶(SOD)水平。Gr I/R 中消失的端粒酶活性在两个治疗组中均升高。同样,两个治疗组的组织病理学评分均较好,但 Gr V-I/R 代表了最佳结果。

结论

我们的研究结果表明,VEGF 无论是在缺血前还是再灌注时应用,对肠 IRI 后的局部损伤均有效。通过解释生化分析和组织病理学发现,我们根据肠 IRI 的原因得出了两种治疗选择。

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