Antifibrotic Agent Pirfenidone Protects against Development o Radiation-Induced Pulmonary Fibrosis in a Murine Model
Antifibrotic Agent Pirfenidone Protects against Development o Radiation-Induced Pulmonary Fibrosis in a Murine Model
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抗纤维化药物吡非尼酮可防止小鼠模型中辐射诱发的肺纤维化的发展
DOI：
10.1667/rr15017.1
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发表时间：
2018-10-01
影响因子：
3.4
通讯作者：
Yuan, Xianglin
中科院分区：
文献类型：
--
作者：
Qin, Wan;Liu, Bo;Yuan, Xianglin
辐射引起的呼吸系统并发症是胸部放射治疗的常见副作用，没有可行的治疗方案。在这里，我们研究了孤儿药物吡非尼酮治疗放射性肺纤维化的潜在疗效。C57BL/6小鼠胸腔内一次性接受16Gy射线照射，随后给予300 mg/kg/d的吡非尼酮治疗四周。对小鼠的存活率和体重进行量化。采用Micro-CT活体肺成像技术动态观察肺纤维化的发展过程。在实验结束时切除肺，并评估组织学变化。与未接受吡非尼酮照射的小鼠相比，照射后接受吡非尼酮治疗的小鼠的中位存活时间延长(140天比73天，P<；0.01)。吡非尼酮治疗可减轻照射后肺组织胶原沉积和纤维化程度。吡非尼酮还可降低肺组织中转化生长因子β1的表达和Smad3的磷酸化。本研究中使用的吡非尼酮剂量水平可减轻受照小鼠的肺纤维化，延长受照小鼠的寿命。它可能为治疗或减少放射性肺纤维化提供一种有前途的方法。
Radiation-induced complications of the respiratory system are a common side effect of thoracic radiotherapy with no viable treatment option. Here, we investigated the potential therapeutic effect of the orphan drug pirfenidone for treating radiation-induced pulmonary fibrosis. C57BL/6 mice received a single fraction of 16 Gy to the thorax and were subsequently treated with 300 mg/kg/day pirfenidone for four weeks. Survival and body weight of the mice were quantified. Micro-CT in vivo lung imaging was performed to dynamically observe the developmental process of pulmonary fibrosis. The lungs were excised at the end of the experiment and evaluated for histological changes. Compared to the irradiated mice that received no pirfenidone, mice treated with pirfenidone after irradiation had an extended median survival time (>140 days vs. 73 days, P < 0.01). The accumulation of collagen and fibrosis in lung tissues after irradiation was decreased with pirfenidone treatment. Pirfenidone also reduced the expression of TGF-β1 and phosphorylation of Smad3 in lung tissues. The dose level of Pirfenidone used in this study attenuated pulmonary fibrosis and prolonged the life span of irradiated mice. It may offer a promising approach to treat or minimize radiation-induced pulmonary fibrosis.