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Eur J Cardiothorac Surg 2006;30:77-84
© 2006 Elsevier Science NL

P38 mitogen-activated protein kinase inhibition attenuates pulmonary inflammatory response in a rat cardiopulmonary bypass model

Research Center for Congenital Heart Disease in FuWai Hospital, The Ministry of Health and Department of Cardiovascular Surgery, Cardiovascular Institute and FuWai Hospital, CAMS and PUMC, Beijing 100037, PR China

Received 14 September 2005; received in revised form 15 January 2006; accepted 14 February 2006.

^_* Corresponding author. Tel.: +86 10 86369800; fax: +86 10 88398496. (Email: dongshi22000{at}yahoo.com.cn).

Objective: Cardiopulmonary bypass (CPB) produces an inflammatory response associated with pulmonary dysfunction. P38 mitogen-activated protein kinase (P38MAPK) have been shown to mediate pulmonary inflammatory response after CPB, we examined the effect of SB203580, a specific p38 MAPK inhibitor, on CPB-induced pulmonary inflammatory response. Methods: Sprague–Dawley rats (n = 54) were randomized into three groups (each n = 18): (1) S group, rats underwent sham CPB; (2) CPB group, rats underwent CPB; (3) SB group, rats underwent CPB plus pretreatment with SB203580 (10 mg/kg, i.v., 30 min before CPB). The lung samples were collected after 10 min, 60 min, and 150 min lung reperfusion (each n = 6) in CPB group and SB group, and after 70 min, 120 min, and 210 min observation in S group as the control. Results: The level of lung phospho-IB, nuclear factor (NF)-B activity and activating protein (AP)-1 activity in CPB group was increased than S group. CPB resulted in increased pulmonary tissue tumor necrosis factor (TNF)- and interleukin (IL)-1ß expression and production, increased pulmonary inflammatory response. The in vivo administration of SB203580 prevented up-regulation of lung-phosphorylated p38 MAP kinase, decreased pulmonary tissue level of proinflammatory cytokines expression and production, and reduced lung inflammation. Conclusions: These findings suggested that (1) p38 MAP kinase activation is one of the important aspects of the signaling event that mediate the release of TNF- and IL-1ß and contributes to CPB-induced pulmonary inflammatory response, (2) SB203580 selectively inhibiting p38 MAP kinase activation efficaciously reduces pulmonary inflammatory response after CPB, and (3) p38 MAP kinase influence the activation of NF-B in the lung during and after CPB.

Key Words: Cardiopulmonary bypass (CPB) • p38 mitogen-activated protein (MAP) kinase • Tumor necrosis factor- • Interleukin-1ß • Pulmonary inflammatory response • Nuclear factor (NF)-B

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