Meng Fan-You, Gao Wei, Ju Ying-Nan
Department of Anesthesiology, the Second Affiliated Hospital of the Harbin Medical University, Harbin, 150081, Heilongjiang Province, China.
Department of Intensive Care Unit, the Third Affiliated Hospital of the Harbin Medical University, Harbin, 150081, Heilongjiang Province, China.
BMC Pharmacol Toxicol. 2017 Mar 29;18(1):25. doi: 10.1186/s40360-017-0131-z.
Cyclooxygenase-2 (COX-2) contributes to ventilation induced lung injury (VILI) and acute respiratory distress syndrome (ARDS). The objective of present study was to observe the therapeutic effect of parecoxib on VILI in ARDS.
In this parallel controlled study performed at Harbin Medical University, China between January 2016 and March 2016, 24 rats were randomly allocated into sham group (S), volume ventilation group/ARDS (VA), parecoxib/volume ventilation group/ARDS (PVA). Rats in the S group only received anesthesia; rats in the VA and PVA group received intravenous injection of endotoxin to induce ARDS, and then received ventilation. Rats in the VA and PVA groups were treated with intravenous injection of saline or parecoxib. The ratio of arterial oxygen pressure to fractional inspired oxygen (PaO/FiO), the wet to dry weight ratio of lung tissue, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), and histopathologic analyses of lung tissue were examined. In addition, survival was calculated at 24 h after VILI.
Compared to the VA group, in the PVA group, PaO/FiO was significantly increased; lung tissue wet to dry weight ratio; macrophage and neutrophil counts, total protein and neutrophil elastase levels in BALF; tumor necrosis factor-α, interleukin-1β, and prostaglandin E levels in BALF and serum; and myeloperoxidase (MPO) activity, malondialdehyde levels, and Bax and COX-2 protein levels in lung tissue were significantly decreased, while Bcl-2 protein levels were significantly increased. Lung histopathogical changes and apoptosis were reduced by parecpxib in the PVA group. Survival was increased in the PVA group.
Parecoxib improves gas exchange and epithelial permeability, decreases edema, reduces local and systemic inflammation, ameliorates lung injury and apoptosis, and increases survival in a rat model of VILI.
环氧化酶-2(COX-2)参与呼吸机所致肺损伤(VILI)和急性呼吸窘迫综合征(ARDS)的发生发展。本研究旨在观察帕瑞昔布对ARDS中VILI的治疗作用。
本平行对照研究于2016年1月至2016年3月在中国哈尔滨医科大学进行,将24只大鼠随机分为假手术组(S)、容量通气组/ARDS(VA)、帕瑞昔布/容量通气组/ARDS(PVA)。S组大鼠仅接受麻醉;VA组和PVA组大鼠静脉注射内毒素诱导ARDS,随后进行通气。VA组和PVA组大鼠分别静脉注射生理盐水或帕瑞昔布进行治疗。检测动脉血氧分压与吸入氧分数之比(PaO/FiO)、肺组织湿重与干重之比、血清及支气管肺泡灌洗液(BALF)中的炎症因子,以及肺组织的病理组织学分析。此外,计算VILI后24小时的生存率。
与VA组相比,PVA组的PaO/FiO显著升高;肺组织湿重与干重之比、BALF中的巨噬细胞和中性粒细胞计数、总蛋白及中性粒细胞弹性蛋白酶水平、BALF和血清中的肿瘤坏死因子-α、白细胞介素-1β及前列腺素E水平,以及肺组织中的髓过氧化物酶(MPO)活性、丙二醛水平、Bax和COX-2蛋白水平显著降低,而Bcl-2蛋白水平显著升高。PVA组中帕瑞昔布减轻了肺组织病理变化和细胞凋亡。PVA组的生存率提高。
在VILI大鼠模型中,帕瑞昔布可改善气体交换和上皮通透性,减轻水肿,减轻局部和全身炎症,改善肺损伤和细胞凋亡,并提高生存率。