Pan Yongting, Mai Li, He Wenkai, Yang Xuqi, Wu Enting, Zhao Jiayuan, Liu Bailiang, Li Mingyan
Nanshan School, Guangzhou Medical University, Guangzhou, China.
Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Front Pharmacol. 2024 Jul 23;15:1436072. doi: 10.3389/fphar.2024.1436072. eCollection 2024.
Peripheral artery disease (PAD) is an increasingly common disease, causing significant complications for patients. Trimetazidine (TMZ) not only improves clinical symptoms in PAD patients but also facilitates angiogenesis in ischemic hind limbs. Our aim was to find the function of TMZ in promoting angiogenesis and tissue perfusion in ischemic rat skeletal muscle. The rats underwent femoral artery ligation (FAL) and then treated with TMZ and saline. Hematoxylin-eosin and Masson's trichrome stain in the ischemic gastrocnemius muscle to analyze muscle morphology and atrophy. To identify angiogenesis and the tissue perfusion, CD31 immunohistochemical staining and laser speckle contrast imaging was conducted. Additionally, hind limb motor ability was measured. Finally, qRT-PCR and Western blotting were used to statistically analyze the expression levels of HIF-1α and VEGF. Our study demonstrated significant enhancement in angiogenesis and tissue perfusion after FAL when treated with TMZ compared to the saline group. Histologically, it mitigates ischemia-induced muscle atrophy and inflammation, as well as reduces fibrosis progression in the TMZ group. Additionally, hind limb motor ability improved in rats treated with TMZ during motor experiments. It suggests that TMZ can promote angiogenesis and improve tissue perfusion in ischemic skeletal muscle of rats by activating the HIF-1α/VEGF signaling pathway. Additionally, it leads to significant improvement in ischemia-induced motor limitations in the hind limbs of rats.
外周动脉疾病（PAD）是一种日益常见的疾病，给患者带来严重并发症。曲美他嗪（TMZ）不仅能改善PAD患者的临床症状，还能促进缺血后肢的血管生成。我们的目的是探究TMZ在促进缺血大鼠骨骼肌血管生成和组织灌注中的作用。对大鼠进行股动脉结扎（FAL），然后用TMZ和生理盐水进行治疗。对缺血的腓肠肌进行苏木精-伊红染色和Masson三色染色，以分析肌肉形态和萎缩情况。为了识别血管生成和组织灌注，进行了CD31免疫组织化学染色和激光散斑对比成像。此外，还测量了后肢运动能力。最后，使用qRT-PCR和蛋白质印迹法对HIF-1α和VEGF的表达水平进行统计学分析。我们的研究表明，与生理盐水组相比，用TMZ治疗FAL后，血管生成和组织灌注有显著增强。组织学上，它减轻了缺血诱导的肌肉萎缩和炎症，并且在TMZ组中减少了纤维化进展。此外，在运动实验中，用TMZ治疗的大鼠后肢运动能力有所改善。这表明TMZ可以通过激活HIF-1α/VEGF信号通路促进大鼠缺血骨骼肌的血管生成并改善组织灌注。此外，它还能显著改善大鼠后肢缺血诱导的运动受限情况。
