吡非尼酮减轻大鼠小肠缺血再灌注损伤。

Pirfenidone attenuates ischaemia-reperfusion injury in the rat small intestine.

Arumugam Thiruma V, Shiels Ian A, Margolin Solomon B, Taylor Stephen M, Brown Lindsay

Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.

Clin Exp Pharmacol Physiol. 2002 Nov;29(11):996-1000. doi: 10.1046/j.1440-1681.2002.03766.x.

Abstract

Pirfenidone, an antifibrotic compound with anti-inflammatory effects, has been investigated in a rat model of acute experimental ischaemia-reperfusion injury of the small intestine. 2. Occlusion of the superior mesenteric artery in young adult female rats for 30 min followed by reperfusion for 120 min induced significant local and systemic effects, including tissue haemorrhage with oedema, elevated serum concentrations of tumour necrosis factor (TNF)-alpha, neutropenia, hypotension and bradycardia. 3. Administration of pirfenidone (200 mg/kg, p.o., i.v. or i.p.) 30 min before occlusion completely inhibited the increase in serum TNF-alpha concentrations. Pirfenidone inhibited, but did not completely prevent, tissue damage in the small intestine, as well as hypotension and oedema, but neutropenia and bradycardia were not significantly changed by treatment. 4. Thus, pirfenidone effectively moderates both local and some systemic effects of ischaemia-reperfusion injury in the rat small intestine model.

摘要

吡非尼酮是一种具有抗炎作用的抗纤维化化合物，已在大鼠急性实验性小肠缺血再灌注损伤模型中进行了研究。2. 对年轻成年雌性大鼠的肠系膜上动脉进行30分钟的阻断，然后再灌注120分钟，会引发显著的局部和全身效应，包括组织出血伴水肿、血清肿瘤坏死因子（TNF）-α浓度升高、中性粒细胞减少、低血压和心动过缓。3. 在阻断前30分钟给予吡非尼酮（200毫克/千克，口服、静脉注射或腹腔注射）可完全抑制血清TNF-α浓度的升高。吡非尼酮可抑制但不能完全预防小肠组织损伤以及低血压和水肿，但治疗后中性粒细胞减少和心动过缓没有明显变化。4. 因此，在大鼠小肠模型中，吡非尼酮可有效减轻缺血再灌注损伤的局部和一些全身效应。