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自由基清除剂依达拉奉对急性胰腺炎相关性肺损伤的保护作用。

Protective effects of the free radical scavenger edaravone on acute pancreatitis-associated lung injury.

机构信息

Department of Anesthesiology, Changhai Hospital, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China.

出版信息

Eur J Pharmacol. 2010 Mar 25;630(1-3):152-7. doi: 10.1016/j.ejphar.2009.12.025. Epub 2009 Dec 24.

Abstract

Impaired lung function is the primary contributor to most deaths associated with severe acute pancreatitis. It is widely accepted that oxidative stress plays a central role in the pathogenesis of pancreatitis and associated complications. Therefore, in the present study, we investigated whether therapeutic treatment with the free radical scavenger edaravone could protect rats against acute pancreatitis and the associated lung injury. Acute pancreatitis was induced by infusion of 1ml/kg of sodium taurocholate (3% solution) into the biliopancreatic duct. Edaravone (8mg/kg) was administered 1h and 13h after inducing pancreatitis, the severity of pancreatic and pulmonary injuries was evaluated 24h after inducing pancreatitis. Edaravone treatment significantly reduced the elevated malondialdehyde levels in rat lungs after acute pancreatitis, suggesting an important role for free radicals in acute pancreatitis-associated lung injury. In addition, edaravone showed significant protective effects against neutrophil infiltration and tissue injury in both pancreas and lung, as demonstrated by serum amylase levels, myeloperoxidase activity and histopathological analysis. Edaravone treatment also attenuated the elevated mRNA levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in rat lungs after acute pancreatitis. In conclusion, edaravone protects rats against acute pancreatitis-associated lung injury, probably through its antioxidant and anti-inflammatory effects. Thus, edaravone shows promise as a treatment for lung injury in patients with acute pancreatitis.

摘要

肺功能障碍是大多数与重症急性胰腺炎相关死亡的主要原因。氧化应激在胰腺炎发病机制及相关并发症中起核心作用,这一观点已被广泛接受。因此,在本研究中,我们研究了自由基清除剂依达拉奉治疗是否可以保护大鼠免受急性胰腺炎及其相关肺损伤。通过向胆胰管内输注 1ml/kg 的牛磺胆酸钠(3%溶液)来诱导急性胰腺炎。在诱导胰腺炎后 1 小时和 13 小时给予依达拉奉(8mg/kg),在诱导胰腺炎后 24 小时评估胰腺和肺损伤的严重程度。依达拉奉治疗可显著降低急性胰腺炎后大鼠肺组织丙二醛水平升高,表明自由基在急性胰腺炎相关肺损伤中起重要作用。此外,依达拉奉对胰腺和肺组织中性粒细胞浸润和组织损伤具有显著的保护作用,这一点可通过血清淀粉酶水平、髓过氧化物酶活性和组织病理学分析来证明。依达拉奉治疗还可减轻急性胰腺炎后大鼠肺组织促炎细胞因子白细胞介素(IL)-6 和肿瘤坏死因子-α(TNF-α)的 mRNA 水平升高。总之,依达拉奉可保护大鼠免受急性胰腺炎相关的肺损伤,可能是通过其抗氧化和抗炎作用。因此,依达拉奉有望成为急性胰腺炎患者肺损伤的治疗药物。

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