Enhanced fibrinolysis protects against lung ischemia-reperfusion injury.
Enhanced fibrinolysis protects against lung ischemia-reperfusion injury.
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DOI：
10.1016/j.jtcvs.2008.12.029
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发表时间：
2009-05
影响因子：
6
通讯作者：
Pinsky, David J.
中科院分区：
文献类型：
--
作者：
Lau, Christine L.;Zhao, Yunge;Kim, Jiyoun;Kron, Irving L.;Sharma, Ashish;Yang, Zequan;Laubach, Victor E.;Linden, Joel;Ailawadi, Gorav;Pinsky, David J.
缺血再灌注损伤（IRI）一直困扰着肺移植领域，导致次优结局。在急性肺损伤过程中，如呼吸机诱导的损伤、败血症或急性呼吸窘迫综合征，血管外纤维蛋白已被证明可促进肺功能障碍和急性炎症反应。本研究探讨了纤溶级联反应在肺IRI中的作用，并探讨了纤溶系统与炎症反应之间的相互作用。缺乏纤溶酶原激活物抑制剂-1基因的小鼠（派-1敲除，派-1 KO;从而增加内源性纤维蛋白的溶解）和野生型小鼠进行原位左肺缺血和再灌注。通过免疫印迹法评价肺中的纤维素含量。通过组织学和生理学参数评估再灌注损伤。采用酶联免疫吸附试验测定支气管肺泡灌洗液和血浆中的促炎介质。缺血-再灌注引起小鼠肺纤维蛋白沉积。与经受相同缺血再灌注条件的野生型小鼠相比，在派-1 KO小鼠中观察到较少的纤维蛋白。根据组织学标准，在野生型中比派-1 KO小鼠中观察到更多的IRI证据（肺泡增厚，肺泡中的细胞浸润）。生理参数也显示了更多的IRI在野生型相比派-1基因敲除小鼠。细胞因子和趋化因子在野生型组中比派-1 KO组升高更多。肺IRI触发鼠肺中的纤维蛋白沉积，并且纤维蛋白产生促炎环境。防止纤维蛋白沉积可减少IRI和炎症。这一发现可能会导致缺血再灌注的新的治疗策略。
Ischemia-reperfusion injury (IRI) continues to plague the field of lung transplantation resulting in suboptimal outcomes. In acute lung injury processes such as ventilator-induced injury, sepsis, or acute respiratory distress syndrome, extravascular fibrin has been shown to promote lung dysfunction and the acute inflammatory response. This study investigates the role of the fibrinolytic cascade in lung IRI and investigates the interplay between the fibrinolytic system and the inflammatory response. Mice lacking the plasminogen activator inhibitor-1 gene (PAI-1 knock out, PAI-1 KO; and thus increased lysis of endogenous fibrin) and wild-type mice underwent in-situ left lung ischemia and reperfusion. Fibrin content in the lung was evaluated by immunoblotting. Reperfusion injury was assessed by histology and physiologic parameters. Proinflammatory mediators were measured in bronchoalveolar lavage fluid and plasma using enzyme-linked immunosorbent assays. Ischemia-reperfusion causes fibrin deposition in murine lungs. Less fibrin was seen in PAI-1 KO mice compared to wild-type mice subjected to the same ischemia-reperfusion conditions. By histologic criteria, more evidence of IRI was noted (thickening of the interstium, cellular infiltration in the alveoli) in the wild type than in PAI-1 KO mice. Physiologic parameters also revealed more IRI in the wild-type compared to PAI-1 KO mice. Cytokine and chemokines were elevated more in the wild-type group than the PAI-1 KO group. Lung IRI triggers fibrin deposition in the murine lungs and fibrin creates a proinflammatory environment. Preventing fibrin deposition may reduce IRI and inflammation. This finding may lead to novel treatment strategies for ischemia-reperfusion.
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影响因子：
2.2
作者：
Nemzek, JA;Siddiqui, J;Remick, DG
通讯作者：
Remick, DG
影响因子：
8.3
作者：
Brown, NJ;Agirbasli, M;Vaughan, DE
通讯作者：
Vaughan, DE
DOI：
10.1164/ajrccm/140.2.287
发表时间：
1989-08-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
MOALLI, R;DOYLE, JM;SALDEEN, T
通讯作者：
SALDEEN, T
DOI：
10.1152/ajplung.00086.2006
发表时间：
2006-11-01
影响因子：
4.9
作者：
Zhao, Minqing;Fernandez, Lucas G.;Laubach, Victor E.
通讯作者：
Laubach, Victor E.
影响因子：
4.6
作者：
Fiser, SM;Tribble, CG;Kron, IL
通讯作者：
Kron, IL