Heme Oxygenase-1 Mediates the Protective Effects of Ischemic Preconditioning on Mitigating Lung Injury Induced by Lower Limb Ischemia-Reperfusion in Rats

• Published in: The Journal of surgical research 2011-05, Vol.167 (2), p.e245-e253
• Main Authors: Peng, Tsui-Chin, M.D, Jan, Woan-Ching, Ph.D, Tsai, Pei-Shan, Ph.D, Huang, Chun-Jen, M.D., Ph.D
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - etiology; Acute Lung Injury - metabolism; Acute Lung Injury - prevention & control; Animals; chemokine; cytokine; Enzyme Inhibitors - pharmacology; heme oxygenase; Heme Oxygenase-1 - antagonists & inhibitors; Heme Oxygenase-1 - physiology; Ischemic Preconditioning; Leukocytes - pathology; Lower Extremity - blood supply; Male; Malondialdehyde - metabolism; Metalloporphyrins - pharmacology; Models, Animal; nitric oxide; Oxidative Stress - physiology; Peroxidase - metabolism; prostaglandin E 2; Protoporphyrins - pharmacology; Rats; Rats, Sprague-Dawley; Reperfusion Injury - complications; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2010.06.010

Background Lower limb ischemia-reperfusion (I/R) imposes oxidative stress, elicits inflammatory response, and subsequently induces acute lung injury. Ischemic preconditioning (IP), a process of transient I/R, mitigates the acute lung injury induced by I/R. We sought to elucidate whether the protective effects of IP involve heme oxygenase-1 (HO-1). Methods Adult male rats were randomized to receive I/R, I/R plus IP, I/R plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) ( n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquet high around each thigh for 3 h followed by reperfusion for 3 h. To achieve IP, three cycles of bilateral lower limb I/R (i.e., ischemia for 10 min followed by reperfusion for 10 min) were performed. IP was performed immediately before I/R. After sacrifice, degree of lung injury was determined. Results Histologic findings, together with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that I/R induced acute lung injury. I/R also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E2 concentrations), imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations), and up-regulated HO-1 expression in lung tissues. IP significantly enhanced HO-1 up-regulation and, in turn, mitigated oxidative stress, inflammatory response, and acute lung injury induced by I/R. In addition, the protective effects of IP were counteracted by SnPP. Conclusions The protective effects of IP on mitigating acute lung injury induced by lower limb I/R are mediated by HO-1.