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七氟醚对氧诱导视网膜病变小鼠模型视网膜血管生成的影响。

The effect of sevoflurane on retinal angiogenesis in a mouse model of oxygen-induced retinopathy.

机构信息

Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, 20, Geumo-ro, Beomeo-ri, Mulgeumeup, Yangsan, 626-770, Republic of Korea.

Department of Pharmacology, Gene and Cell Therapy Center for Vessel-associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Republic of Korea.

出版信息

J Anesth. 2018 Apr;32(2):204-210. doi: 10.1007/s00540-018-2465-0. Epub 2018 Feb 20.

DOI:10.1007/s00540-018-2465-0
PMID:29464332
Abstract

BACKGROUND

Sevoflurane is commonly used in general anesthesia for premature neonates. The main mechanism of retinopathy of prematurity (ROP) is increased levels of vascular endothelial growth factor (VEGF). For the investigation of sevoflurane's effect on angiogenesis, the angiogenesis and VEGF expression in the retina were measured after administering sevoflurane in an oxygen-induced retinopathy mice model.

MATERIALS AND METHODS

The mice were divided into the normoxic group (Nc and Ns group; n = 6) and the ROP group (C, Rc, and Rs group; n = 6). Rc group were exposed to 75% oxygen for 5 days beginning on postnatal day (P) 7, and then returned to room air. Age-matched mice in the C group were exposed to room air. To observe angiogenesis of the retina, the mice were sacrificed on P16. The Rs group was exposed to 2 vol% sevoflurane for 2 h on P12, P13, and P14 with 40% oxygen.

RESULTS

The angiogenic area and the spreading distance of vessels on P4 were statistically decreased in the Ns group, compared to the Nc group. The avascular area on P16 was significantly increased and the expression of VEGF was suppressed in the Rs group compared to the Rc group.

CONCLUSIONS

Sevoflurane can inhibit retinal angiogenesis via suppressing VEGF expression in an OIR mice model with exposure to relative hypoxia. Nevertheless, it is still difficult to apply the results of this study immediately to humans because of the heterogeneity of responses to sevoflurane.

摘要

背景

七氟醚常用于早产儿的全身麻醉。早产儿视网膜病变(ROP)的主要发病机制是血管内皮生长因子(VEGF)水平升高。为了研究七氟醚对血管生成的影响,在氧诱导的视网膜病变小鼠模型中给予七氟醚后,测量了视网膜的血管生成和 VEGF 表达。

材料和方法

将小鼠分为常氧组(Nc 和 Ns 组;n=6)和 ROP 组(C、Rc 和 Rs 组;n=6)。Rc 组于生后第 7 天开始暴露于 75%氧气中 5 天,然后返回室内空气。C 组中年龄匹配的小鼠暴露于室内空气。为了观察视网膜的血管生成,于 P16 处死小鼠。Rs 组于 P12、P13 和 P14 时在 40%氧气中暴露于 2 体积%七氟醚 2 小时。

结果

与 Nc 组相比,Ns 组 P4 时血管生成区和血管延伸距离统计学上降低。与 Rc 组相比,Rs 组 P16 时无血管区明显增加,VEGF 表达受抑制。

结论

在相对低氧暴露的 OIR 小鼠模型中,七氟醚通过抑制 VEGF 表达抑制视网膜血管生成。然而,由于对七氟醚的反应存在异质性,因此很难立即将本研究的结果应用于人类。

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本文引用的文献

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Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage in a rat model via PI3K/Akt signaling pathway.七氟醚预处理通过PI3K/Akt信号通路改善大鼠模型的脑局灶性缺血再灌注损伤。
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Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell carcinoma cell by upregulating the DNA methylation states of the promoter region.
七氟醚通过上调启动子区域的DNA甲基化状态,减弱舌鳞状细胞癌细胞中缺氧诱导的血管内皮生长因子(VEGF)水平。
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Sevoflurane protects against intestinal ischemia-reperfusion injury partly by phosphatidylinositol 3 kinases/Akt pathway in rats.七氟醚部分通过磷脂酰肌醇3激酶/蛋白激酶B信号通路对大鼠肠缺血再灌注损伤起到保护作用。
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Sevoflurane promotes the expansion of glioma stem cells through activation of hypoxia-inducible factors in vitro.七氟醚通过体外激活缺氧诱导因子促进神经胶质瘤干细胞的扩增。
Br J Anaesth. 2015 May;114(5):825-30. doi: 10.1093/bja/aeu402. Epub 2014 Dec 9.
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The potential dual effects of sevoflurane on AKT/GSK3β signaling pathway.七氟醚对AKT/GSK3β信号通路的潜在双重作用。
Med Gas Res. 2014 Mar 3;4(1):5. doi: 10.1186/2045-9912-4-5.
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