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英夫利昔单抗对大鼠肠缺血/再灌注模型急性肺损伤的抗炎和抗氧化作用。

Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a rat model of intestinal ischemia/reperfusion.

机构信息

Department of Pediatrics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.

出版信息

J Mol Histol. 2012 Jun;43(3):361-9. doi: 10.1007/s10735-012-9396-0. Epub 2012 Mar 3.

Abstract

The purpose of this study was to investigate the role of infliximab on acute lung injury induced by intestinal ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered by intravenously. All animals were sacrificed at the end of reperfusion and lung tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no more biochemical and histopathological changes on intestinal I/R injury in rats by infliximab treatment have been reported. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in lung tissues samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall and a great number of inflammatory cells that infiltrated the interstitium and alveoli. Infliximab treatment significantly attenuated the severity of intestinal I/R injury. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase and arise in the expression of surfactant protein D in lung tissue of acute lung injury induced by intestinal I/R with infliximab therapy. It was concluded that infliximab treatment might be beneficial in acute lung injury, therefore, shows potential for clinical use. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects in acute lung injury induced by intestinal I/R.

摘要

本研究旨在探讨英夫利昔单抗对肠缺血/再灌注(I/R)引起的急性肺损伤的作用。将 30 只雄性 Wistar 白化大鼠随机分为三组:假手术组、I/R 组和 I/R+英夫利昔单抗组,每组 10 只。假手术组动物仅行剖腹术而不进行 I/R 损伤。I/R 组动物行剖腹术后,结扎肠系膜上动脉 1 小时,再灌注 1 小时。在英夫利昔单抗组,I/R 前 3 天,经静脉给予英夫利昔单抗(3mg/kg)。所有动物在再灌注结束时处死,采集各组肺组织标本进行生化和组织病理学检查。迄今为止,尚无关于英夫利昔单抗治疗对大鼠肠 I/R 损伤的生化和组织病理学变化的更多报道。英夫利昔单抗治疗可显著降低肺组织中丙二醛水平升高,还原型超氧化物歧化酶和谷胱甘肽过氧化物酶活性增加。肠 I/R 导致严重的组织病理学损伤,包括水肿、出血、肺泡壁增厚和大量炎性细胞浸润间质和肺泡。英夫利昔单抗治疗可显著减轻肠 I/R 损伤的严重程度。此外,英夫利昔单抗治疗可显著降低诱导型一氧化氮合酶的活性,增加肺组织中表面活性蛋白 D 的表达,从而减轻肠 I/R 引起的急性肺损伤。综上所述,英夫利昔单抗治疗可能对急性肺损伤有益,因此具有临床应用潜力。由于其抗炎和抗氧化作用,英夫利昔单抗预处理可能对肠 I/R 引起的急性肺损伤具有保护作用。

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