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氟西汀对大鼠主动脉手术后缺血再灌注的影响。

The effect of fluoxetine on ischemia-reperfusion after aortic surgery in a rat model.

作者信息

Guner Ibrahim, Yaman Muhittin O, Aksu Ugur, Uzun Duygu, Erman Hayriye, Inceli Meliha, Gelisgen Remisa, Yelmen Nermin, Uzun Hafize, Sahin Gulderen

机构信息

Cerrahpasa Medical Faculty, Department of Physiology, Istanbul University, Istanbul, Turkey.

Science Faculty, Department of Biology, Istanbul University, Istanbul, Turkey.

出版信息

J Surg Res. 2014 Jun 1;189(1):96-105. doi: 10.1016/j.jss.2014.02.033. Epub 2014 Feb 22.

DOI:10.1016/j.jss.2014.02.033
PMID:24674837
Abstract

BACKGROUND

Aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute lung injury after abdominal aortic surgery. The aim of the present study was to examine the effect of fluoxetine (Flx), a selective serotonin reuptake inhibitor widely used as a preoperative anxiolytic, on lung injury induced by abdominal aortic IR in rats.

METHODS

Wistar rats were randomized into three groups (n = 7 per group): (1) control (sham laparotomy); (2) IR without Flx (60-min ischemia and 120-min reperfusion); (3) IR with Flx (Flx + IR) (Flx 20 mg/kg/d, intraperitoneally for 3 d before surgery). Lung tissue samples and bronchoalveolar lavage (BAL) were obtained for biochemical analysis of oxidative status. Ischemia-modified albumin (IMA) level and protein concentrations in BAL and lung wet to dry weight ratios were determined. Histologic evaluation of the lung tissues was also performed.

RESULTS

IR without Flx led to significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant-antioxidant balance and decrease in superoxide dismutase, glutathione, and ferric reducing antioxidant power activities (P < 0.05 versus control), whereas Flx was able to restore these parameters (P > 0.05 versus control) and decrease IMA level (P < 0.01 versus control) and protein concentration (P < 0.05 versus control) in BAL and wet to dry lung weight ratio. Histologic evaluation showed that Flx attenuated the morphologic changes associated with lung injury.

CONCLUSIONS

The results indicate that Flx confers protection against aortic IR-induced lung oxidative stress and cellular integrity. IMA levels in BAL may be used as a follow-up marker for the efficacy of treatment in lung injury.

摘要

背景

主动脉缺血再灌注(IR)是腹主动脉手术后发生术后急性肺损伤的一个重要因素。本研究的目的是探讨氟西汀(Flx),一种广泛用作术前抗焦虑药的选择性5-羟色胺再摄取抑制剂,对大鼠腹主动脉IR诱导的肺损伤的影响。

方法

将Wistar大鼠随机分为三组(每组n = 7):(1)对照组(假手术);(2)无氟西汀的IR组(60分钟缺血和120分钟再灌注);(3)氟西汀+ IR组(手术前3天腹腔注射氟西汀20mg/kg/d)。获取肺组织样本和支气管肺泡灌洗(BAL)样本用于氧化状态的生化分析。测定缺血修饰白蛋白(IMA)水平、BAL中的蛋白质浓度以及肺湿重与干重之比。还对肺组织进行了组织学评估。

结果

无氟西汀的IR导致脂质过氧化氢、丙二醛和促氧化剂-抗氧化剂平衡显著增加,超氧化物歧化酶、谷胱甘肽和铁还原抗氧化能力活性降低(与对照组相比,P < 0.05),而氟西汀能够恢复这些参数(与对照组相比,P > 0.05),并降低BAL中的IMA水平(与对照组相比,P < 0.01)、蛋白质浓度(与对照组相比,P < 0.05)以及肺湿重与干重之比。组织学评估显示氟西汀减轻了与肺损伤相关的形态学变化。

结论

结果表明氟西汀可对主动脉IR诱导的肺氧化应激和细胞完整性提供保护。BAL中的IMA水平可作为肺损伤治疗效果的随访标志物。

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