Division of Endocrinology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, PR China.
Branch of national clinical research center for metabolic diseases, Hubei, PR China.
Ann Med. 2021 Dec;53(1):1099-1107. doi: 10.1080/07853890.2021.1925147.
Ischaemia caused by lower extremity artery stenosis is the main cause of peripheral artery disease (PAD) in patients with diabetes. Trimetazidine (TMZ) has traditionally been used as an anti-ischaemic drug for coronary artery disease. The effect of TMZ on PAD in a diabetic animal model and the underlying molecular mechanisms remain unclear.
The db/db mice were challenged with femoral artery ligation (FAL), followed by TMZ treatment for 2 weeks. Scores on hindlimb ischaemia and function were evaluated. Histological and capillary density analyses of gastrocnemius were performed. The expression of vascular endothelial growth factor (VEGF) and myogenic regulators was also confirmed by Western blotting. We also detected serum intercellular adhesion molecule 1 (ICAM-1) level through ELISA.
Diabetic mice exhibited limb ulceration and motor dysfunction after FAL while TMZ-treated db/db mice exhibited milder ischaemic impairment. Furthermore, decreased capillary density in the gastrocnemius muscles of ischaemic hindlimb and reduced expressions of VEGF, myogenic markers, and serum ICAM-1 could be partially reversed by TMZ treatment.
TMZ may alleviate hindlimb ischaemic damage in db/db mice, at least partly, through enhancing angiogenesis and promoting myogenesis in ischaemia region.Key messagesTMZ intervention could alleviate hindlimb ischaemic damage in db/db mice.TMZ intervention could enhance angiogenesis and stimulate myogenesis in ischaemia region.
下肢动脉狭窄引起的缺血是糖尿病患者外周动脉疾病（PAD）的主要原因。曲美他嗪（TMZ）传统上被用作治疗冠状动脉疾病的抗缺血药物。TMZ 对糖尿病动物模型中 PAD 的影响及其潜在的分子机制尚不清楚。
db/db 小鼠接受股动脉结扎（FAL）挑战，随后 TMZ 治疗 2 周。评估后肢缺血和功能的评分。对腓肠肌进行组织学和毛细血管密度分析。通过 Western blot 还证实了血管内皮生长因子（VEGF）和肌生成调节剂的表达。我们还通过 ELISA 检测了血清细胞间黏附分子 1（ICAM-1）水平。
糖尿病小鼠在 FAL 后出现肢体溃疡和运动功能障碍，而 TMZ 治疗的 db/db 小鼠缺血性损伤较轻。此外，缺血后肢腓肠肌中毛细血管密度降低，VEGF、肌生成标志物和血清 ICAM-1 的表达减少，可部分被 TMZ 治疗逆转。
TMZ 可能通过增强血管生成和促进缺血部位的肌生成，部分缓解 db/db 小鼠的后肢缺血损伤。
关键信息TMZ 干预可减轻 db/db 小鼠的后肢缺血损伤。TMZ 干预可增强血管生成并刺激缺血部位的肌生成。
