Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Acta Physiol (Oxf). 2024 Jul;240(7):e14163. doi: 10.1111/apha.14163. Epub 2024 May 16.
To reveal the contribution of Irisin in the beneficial effects of resistance exercise on myocardial fibrosis (MF) and cardiac function in the mice with myocardial infarction (MI).
The MI model was built by ligating the left anterior descending coronary artery in Fndc5 knockout mice (Fndc5). Resistance exercise was started one week after surgery and continued for four weeks. In addition, HO, AICAR, recombinant human Irisin protein (rhIRISIN), and Sirt1 shRNA lentivirus (LV-Sirt1 shRNA) were used to intervene primary isolated cardiac fibroblasts (CFs). MF was observed through Masson staining, and apoptosis was assessed using TUNEL staining. MDA and T-SOD contents were detected by biochemical kits. The expression of proteins and genes was detected by Western blotting and RT-qPCR.
Resistance exercise increased Fndc5 mRNA level, inhibited the activation of TGFβ1-TGFβR2-Smad2/3 pathway, activated AMPK-Sirt1 pathway, reduced the levels of oxidative stress, apoptosis, and MF in the infarcted heart, and promoted cardiac function. However, Fndc5 knockout attenuated the protective effects of resistance exercise on the MI heart. Results of the in vitro experiments showed that AICAR and rhIRISIN intervention activated the AMPK-Sirt1 pathway and inactivated the TGFβ1-Smad2/3 pathway, and promoted apoptosis in HO-treated CFs. Notably, these effects of rhIRISIN intervention, except for the TGFβR2 expression, were attenuated by LV-Sirt1 shRNA.
Resistance exercise upregulates Fndc5 expression, activates AMPK-Sirt1 pathway, inhibits the activation of TGFβ1-Smad2/3 pathway, attenuates MF, and promotes cardiac function after MI.
揭示鸢尾素在抵抗运动对心肌梗死（MI）小鼠心肌纤维化（MF）和心脏功能的有益作用中的贡献。
通过结扎 Fndc5 基因敲除小鼠（Fndc5）的左前降支冠状动脉构建 MI 模型。手术后一周开始进行抵抗运动，并持续四周。此外，使用 HO、AICAR、重组人鸢尾素蛋白（rhIRISIN）和 Sirt1 shRNA 慢病毒（LV-Sirt1 shRNA）干预原代分离的心肌成纤维细胞（CFs）。通过 Masson 染色观察 MF，通过 TUNEL 染色评估细胞凋亡。通过生化试剂盒检测 MDA 和 T-SOD 含量。通过 Western blot 和 RT-qPCR 检测蛋白和基因的表达。
抵抗运动增加了 Fndc5 mRNA 水平，抑制了 TGFβ1-TGFβR2-Smad2/3 途径的激活，激活了 AMPK-Sirt1 途径，降低了氧化应激、凋亡、MF 的水平，并促进了心脏功能。然而，Fndc5 基因敲除削弱了抵抗运动对 MI 心脏的保护作用。体外实验结果表明，AICAR 和 rhIRISIN 干预激活了 AMPK-Sirt1 途径并抑制了 TGFβ1-Smad2/3 途径，促进了 HO 处理的 CFs 中的细胞凋亡。值得注意的是，除了 TGFβR2 表达外，rhIRISIN 干预的这些作用均被 LV-Sirt1 shRNA 削弱。
抵抗运动上调 Fndc5 表达，激活 AMPK-Sirt1 途径，抑制 TGFβ1-Smad2/3 途径的激活，减轻 MF，并促进 MI 后心脏功能的恢复。
