Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
J Thorac Cardiovasc Surg. 2019 Jul;158(1):289-296. doi: 10.1016/j.jtcvs.2018.08.098. Epub 2018 Sep 28.
Lung ischemia-reperfusion injury is among the complications seen after lung transplantation, resulting in morbidity and mortality. Pirfenidone, an antifibrotic agent for the treatment of idiopathic pulmonary fibrosis, is reported to have cytoprotective properties in various disease models. The purpose of this study was to investigate the effect of pirfenidone on lung ischemia-reperfusion injury.
Male Lewis rats (260-290 g) were divided into 3 groups: sham group (n = 5), warm ischemia (WI) group (n = 10), and WI plus pirfenidone (WI+PFD) group (n = 10). The sham group underwent 210 minutes of perfusion without ischemia. The WI and WI+PFD groups underwent 90 minutes of warm ischemia and 120 minutes of reperfusion. In the WI+PFD group, pirfenidone (300 mg/kg) was administered orally by gavage 30 minutes before ischemia. After reperfusion, arterial blood gas analysis, lung mechanics, lung wet-to-dry weight ratio, and histologic findings were obtained. The gene expressions of proinflammatory cytokines in lung tissue were measured by quantitative reverse transcription polymerase chain reaction.
Compared with the WI group, the WI+PFD group had significantly better dynamic pulmonary compliance (P < .01) and oxygenation levels (P < .05). The wet-to-dry ratio was lower in the WI+PFD group (P < .05). Histologic analysis showed that the WI+PFD group had reduced perivascular edema and neutrophil infiltration. The expression of tumor necrosis factor-α messenger RNA was decreased in the WI+PFD group (P < .05).
Our results revealed that in a rat hilar clamp model, pirfenidone alleviated lung ischemia-reperfusion through anti-inflammatory effects.
肺缺血再灌注损伤是肺移植后出现的并发症之一，可导致发病率和死亡率升高。吡非尼酮是一种治疗特发性肺纤维化的抗纤维化药物，据报道在各种疾病模型中具有细胞保护作用。本研究旨在探讨吡非尼酮对肺缺血再灌注损伤的影响。
雄性 Lewis 大鼠（260-290g）分为 3 组：假手术组（n=5）、热缺血组（n=10）和热缺血加吡非尼酮组（n=10）。假手术组仅进行 210 分钟的灌注而不进行缺血。热缺血组和热缺血加吡非尼酮组进行 90 分钟的热缺血和 120 分钟的再灌注。在热缺血加吡非尼酮组中，吡非尼酮（300mg/kg）在缺血前 30 分钟经灌胃给药。再灌注后，进行动脉血气分析、肺力学、肺湿重/干重比和组织学检查，并通过定量逆转录聚合酶链反应测量肺组织中促炎细胞因子的基因表达。
与热缺血组相比，热缺血加吡非尼酮组的动态肺顺应性显著改善（P<0.01），氧合水平也更好（P<0.05）。热缺血加吡非尼酮组的湿重/干重比较低（P<0.05）。组织学分析显示，热缺血加吡非尼酮组的血管周围水肿和中性粒细胞浸润减少。热缺血加吡非尼酮组肿瘤坏死因子-α信使 RNA 的表达降低（P<0.05）。
本研究结果表明，在大鼠肺门夹闭模型中，吡非尼酮通过抗炎作用缓解肺缺血再灌注损伤。
