Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Department of Geriatrics, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Physiol Rep. 2024 Dec;12(23):e70149. doi: 10.14814/phy2.70149.
N-butylphthalide (NBP) has been reported to have potential protective effects in ischemic stroke via its antioxidative properties. The present study was aimed to investigate the protective effects of NBP on ischemia/reperfusion (I/R)-induced skeletal muscle injury. Mouse model of I/R-induced skeletal muscle injury and hypoxia/reoxygenation (H/R)-induced C2C12 myotube injury model were constructed to test the protective effects of NBP both in vivo and in vitro. Our results showed that I/R resulted in skeletal muscle injury, as evidenced by elevated levels of LDH, CK, ROS, 3-NT, MDA, and 4-HNE as well as decreased activities of SOD, GSH-Px, and decreased expression of Myog and MyoD in gastrocnemius muscle, which was ameliorated by NBP treatment. Mechanistically, NBP treatment increased the expression of Sirt1 and Nrf2 in the injured skeletal muscle. Notably, the protective effects of NBP on I/R-induced skeletal muscle injury was diminished by the treatment of Sirt1 inhibitor. Further studies in H/R-induced C2C12 myotubes injury model also showed that NBP activated the Sirt1/Nrf2 pathway. NBP treatment upregulated the expression of myog and MyoD in H/R-stimulated C2C12 myotubes, which was eliminated by silencing of Sirt1. Taken together, our results suggest that NBP may alleviated I/R-induced skeletal muscle injury by activating Sirt1/Nrf2 signaling pathway.
正丁基苯酞（NBP）已被报道具有抗氧化特性，可对缺血性中风起到潜在的保护作用。本研究旨在探讨 NBP 对缺血/再灌注（I/R）诱导的骨骼肌损伤的保护作用。构建了 I/R 诱导的骨骼肌损伤小鼠模型和缺氧/复氧（H/R）诱导的 C2C12 肌管损伤模型，以测试 NBP 在体内和体外的保护作用。我们的结果表明，I/R 导致骨骼肌损伤，这表现在肌酸激酶（CK）、乳酸脱氢酶（LDH）、活性氧（ROS）、3-硝基酪氨酸（3-NT）、丙二醛（MDA）和 4-羟基壬烯酸（4-HNE）水平升高，以及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性降低，肌球蛋白（Myog）和肌细胞生成素（MyoD）表达减少，而 NBP 处理可改善这些损伤。机制上，NBP 处理增加了损伤骨骼肌中 Sirt1 和 Nrf2 的表达。值得注意的是，Sirt1 抑制剂处理可减弱 NBP 对 I/R 诱导的骨骼肌损伤的保护作用。在 H/R 诱导的 C2C12 肌管损伤模型中的进一步研究也表明，NBP 激活了 Sirt1/Nrf2 通路。NBP 处理上调了 H/R 刺激的 C2C12 肌管中 Myog 和 MyoD 的表达，而 Sirt1 的沉默消除了这种上调。总之，我们的结果表明，NBP 可能通过激活 Sirt1/Nrf2 信号通路缓解 I/R 诱导的骨骼肌损伤。
