Department of Surgery of Ruijin Hospital, Shanghai JiaoTong University, Shanghai Institute of Digestive Surgery, Shanghai 200025, PR China.
Int Immunopharmacol. 2011 Jan;11(1):96-102. doi: 10.1016/j.intimp.2010.10.012. Epub 2010 Oct 30.
Edaravone (MCI-186) is a potent free radical scavenger used clinically to treat acute brain infarction. Its antioxidant ability maybe also do favor to protect against lung injury. In this study, we evaluated whether edaravone could protect against lung injury and pulmonary fibrosis in paraquat-treated rats. Rats were divided into four groups (Control group, Edaravone group, Paraquat intoxication group and Paraquat+Edaravone group) and sacrificed on day 1, 3, 5, 7, 14 and 28. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected and analyzed biochemically and histologically. Paraquat intoxication significantly increased malondialdehyde (MDA), hydroproline, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in lung tissue and BALF, and also increased mRNA expression of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in lung tissue, but decreased SOD and GSH-PX activity in lung tissue and BALF. Histological examination of paraquat-treated rats showed acute injury with interstitial edema and widespread inflammatory cell infiltration in the alveolar space and septum, as well as fibrosis. After edaravone treatment, levels of MDA, IL-6, TNF-α and hydroproline decreased, but SOD and GSH-PX activity in lung tissue and BALF increased. In addition, the mRNA expression of TGF-β1, MMP-2, and TIMP-1 down-regulated. Histological examination showed that edaravone decreased interstitial edema, inflammatory cell infiltration and prevented the process of pulmonary fibrosis.
依达拉奉（MCI-186）是一种有效的自由基清除剂，临床上用于治疗急性脑梗死。其抗氧化能力可能也有利于防止肺损伤。在这项研究中，我们评估了依达拉奉是否可以防止百草枯中毒大鼠的肺损伤和肺纤维化。大鼠分为四组（对照组、依达拉奉组、百草枯中毒组和百草枯+依达拉奉组），并于第 1、3、5、7、14 和 28 天处死。收集肺组织和支气管肺泡灌洗液（BALF），并进行生化和组织学分析。百草枯中毒显著增加肺组织和 BALF 中的丙二醛（MDA）、羟脯氨酸、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平，也增加肺组织中转化生长因子-β1（TGF-β1）、基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制剂-1（TIMP-1）的 mRNA 表达，但降低肺组织和 BALF 中的 SOD 和 GSH-PX 活性。百草枯中毒大鼠的组织学检查显示急性损伤，肺泡空间和隔室间质水肿和广泛的炎症细胞浸润，以及纤维化。依达拉奉治疗后，MDA、IL-6、TNF-α和羟脯氨酸水平降低，而肺组织和 BALF 中的 SOD 和 GSH-PX 活性增加。此外，TGF-β1、MMP-2 和 TIMP-1 的 mRNA 表达下调。组织学检查显示，依达拉奉减少了间质水肿、炎症细胞浸润，并阻止了肺纤维化的进程。
