Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of heme oxygenase-1

作者：Zuidema Mozow Y; Peyton Kelly J; Fay William P; Durante William; Korthuis Ronald J^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2011, 301(3): H888-H894.

DOI：10.1152/ajpheart.00432.2010

• ischemia
• reperfusion
• leukocyte rolling
• leukocyte adhesion
• hemin

Zuidema MY, Peyton KJ, Fay WP, Durante W, Korthuis RJ. Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of heme oxygenase-1. Am J Physiol Heart Circ Physiol 301: H888-H894, 2011. First published June 10, 2011; doi:10.1152/ajpheart.00432.2010.-We recently demonstrated that preconditioning with an exogenous hydrogen sulfide donor (NaHS-PC) 24 h before ischemia and reperfusion (I/R) causes postcapillary venules to shift to an anti-inflammatory phenotype in C57BL/6J wild-type (WT) mice such that these vessels fail to support increases in postischemic leukocyte rolling (LR) and leukocyte adhesion (LA). The objective of the present study was to determine whether heme oxygenase-1 (HO-1) is a mediator of these anti-inflammatory effects noted during I/R in mice preconditioned with NaHS. Intravital fluorescence microscopy was used to visualize LR and LA in single postcapillary venules of the murine small intestine. I/R induced marked increases in LR and LA, effects that were prevented by NaHS-PC. Treatment with the HO inhibitor tin protoporphyrin IX, but not the inactive protoporphyrin CuPPIX, just before reperfusion prevented the anti-inflammatory effects of antecedent NaHS. The anti-inflammatory effects of NaHS-PC were mimicked by preconditioning with hemin, an agent that induces HO-1 expression. We then evaluated the effect of NaHS as a preconditioning stimulus in mice that were genetically deficient in HO-1 (HO-1(-/-) on an H129 background with appropriate WT strain controls). NaHS-PC was ineffective in HO-1(-/-) mice. Our work indicates that HO-1 serves as an effector of the anti-inflammatory effects of NaHS-PC during I/R 24 h later.

• 出版日期2011-9