title: Pentoxifylline inhibits pulmonary inflammation induced by infrarenal aorticcross-clamping dependent of adenosine receptor A2A.
abstract: Infrarenal aortic cross-clamping (IAC) is commonly used during infrarenal vascular operations. Prolonged IAC causes ischemia-reperfusion injury to local tissues, resulting in the release of inflammatory cytokines and acute lung injury (ALI). Pentoxifylline (PTX) is a clinically used drug for chronic occlusive arterial diseases and exerts protective effects against ALI induced by various factors in experimental models. In this study, we evaluated the protective effects of PTX in a rat model of IAC. Wistar rats underwent IAC for 2 h, followed by 4 h reperfusion. PTX alone, or in combination with ZM-241385 (an adenosine receptor A2A antagonist) or CGS-21680 (an A2A agonist), was pre-administered to rats 1 h prior to IAC, and the severity of lung injury and inflammation were examined. Administration of PTX significantly attenuated ALI induced by IAC, evidenced by reduced histological scores and wet lung contents, improved blood gas parameters, decreased cell counts and protein amounts in bronchoalveolar lavage fluids, and inhibition of MPO activity and ICAM-1 expression in lung tissues, and lower plasma levels of TNF-α, IL-6, IL-1β and soluble ICAM-1. ZM-241385 significantly abrogated, while CGS-21680 slightly enhanced, the effects of PTX in ameliorating ALI and inhibiting pulmonary inflammation. In exploration of the mechanisms, we found that PTX stimulated IL-10 production through the phosphorylation of STAT3, and A2A receptor participated in this regulation. The study indicates PTX plays a protective role in IAC-induced ALI in rats by inhibiting pulmonary inflammation through A2A signaling pathways.
authors.affiliation: The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical UniversityHarbin 150001, China; Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical UniversityHarbin 150001, China.
authors.forename: Hali
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University Harbin 150001, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Tan
authors.affiliation: Department of General Surgery, The Fifth Affiliated Hospital of Harbin Medical University Daqing 163319, China.
authors.forename: Liquan
authors.initials: L
authors.lastname: Tong
authors.affiliation: The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical UniversityHarbin 150001, China; Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical UniversityHarbin 150001, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of General Surgery, The Fifth Affiliated Hospital of Harbin Medical University Daqing 163319, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University Harbin 150001, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University Harbin 150001, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Sun
keywords: Infrarenal aortic cross-clamping; acute lung injury; adenosine A2A receptor; ischemia reperfusion injury; pentoxifylline; tumor necrosis factor-α