title: Lipoxin A4 pretreatment mitigates skeletal muscle ischemia-reperfusion injury in rats.
abstract: The aim of this study was to investigate the protective effects and underlying anti-oxidative molecular mechanism of lipoxin A4 (LA4) in rats with ischemia/reperfusion (I/R)-injured skeletal muscle. A rat model of I/R-injured skeletal muscle was obtained by subjecting rats to a 3-h ligation of the right femoral artery followed by 3 h of reperfusion. Treatment with LA4 significantly ameliorated histological damage scores in I/R-injured skeletal muscle. LA4 treatment resulted in remarkable decreases in the wet weight/dry weight ratio (W/D ratio), inflammatory response, oxidative stress, and cell apoptosis. In addition, treatment with LA4 was accompanied by a prominently enhanced nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and expression of heme oxygenase 1 (HO-1) in the I/R-injured skeletal muscle. However, these protective effects were reversed by zinc protoporphyrin-IX (ZnPP), a specific HO-1 inhibitor. Our study shows that LA4 may have the potential as a therapeutic agent for I/R-injured muscle tissue via activation of the Nrf2/HO-1 signaling pathway.
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University Shanghai, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zong
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules and Research Center on Aging and Medicine, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University Shanghai, China.
authors.forename: Haodong
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University Shanghai, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Pharmacy, Pudong Hospital, Fudan University Shanghai 201399, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Ma
keywords: Ischemia-reperfusion injury; Nrf2/HO-1 signaling pathway; apoptosis; inflammatory response; lipoxin A4; oxidative stress; skeletal muscle