Zong Haiyang, Li Xinghui, Lin Haodong, Hou Chunlin, Ma Fenfen
Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University Shanghai, China.
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.
Am J Transl Res. 2017 Mar 15;9(3):1139-1150. eCollection 2017.
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.
本研究旨在探讨脂氧素A4（LA4）对缺血/再灌注（I/R）损伤骨骼肌大鼠的保护作用及其潜在的抗氧化分子机制。通过对大鼠右侧股动脉进行3小时结扎，随后再灌注3小时，建立I/R损伤骨骼肌大鼠模型。LA4治疗显著改善了I/R损伤骨骼肌的组织学损伤评分。LA4治疗导致湿重/干重比（W/D比）、炎症反应、氧化应激和细胞凋亡显著降低。此外，LA4治疗伴随着I/R损伤骨骼肌中核因子红细胞2相关因子2（Nrf2）的核积累和血红素加氧酶1（HO-1）表达的显著增强。然而，这些保护作用被特异性HO-1抑制剂锌原卟啉-IX（ZnPP）逆转。我们的研究表明，LA4可能通过激活Nrf2/HO-1信号通路，具有作为I/R损伤肌肉组织治疗剂的潜力。
