Gu Jiao-Jiao, Hou Yun-Long, Yan Yi-Hui, Li Jie, Wei Ya-Ru, Ma Kun, Wang Xiao-Qi, Zhang Jie-Han, Wang Dan-Dong, Li Cui-Ru, Li Dong-Qi, Sun Ling-Ling, Gao Huai-Lin
Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050090, Hebei Province, China.
Graduate School, Hebei Medical University, Shijiazhuang 050011, Hebei Province, China.
World J Diabetes. 2023 Mar 15;14(3):234-254. doi: 10.4239/wjd.v14.i3.234.
Peripheral arterial disease (PAD) has become one of the leading causes of disa-bility and death in diabetic patients. Restoring blood supply to the hindlimbs, especially by promoting arteriogenesis, is currently the most effective strategy, in which endothelial cells play an important role. Tongxinluo (TXL) has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.
To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.
An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice. Laser Doppler imaging and micro-computed tomography (micro-CT) were performed to assess the recovery of blood flow and arteriogenesis. Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology, Western blot analysis, enzyme-linked immuno-sorbent assay and real-time polymerase chain reaction assays. , human vascular endothelial cells (HUVECs) and human vascular smooth muscle cells (VSMCs) were pretreated with TXL for 4 h, followed by incubation in high glucose and hypoxia conditions to induce cell injury. Then, indicators of HUVEC pyroptosis and function, HUVEC-VSMC interactions and the migration of VSMCs were measured.
Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis. TXL also inhibited endothelial cell pyroptosis the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway. In addition, TXL restored endothelial cell functions, including maintaining the balance of vasodilation, acting as a barrier to reduce inflammation, and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway. Similar results were observed .
TXL has a pro-arteriogenic effect in the treatment of diabetic PAD, and the mechanism may be related to the inhibition of endothelial cell pyroptosis, restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.
外周动脉疾病（PAD）已成为糖尿病患者致残和死亡的主要原因之一。恢复后肢血液供应，特别是通过促进动脉生成，是目前最有效的策略，其中内皮细胞起着重要作用。通心络（TXL）已广泛用于治疗心脑血管疾病，并扩展用于治疗糖尿病相关血管疾病。
研究通心络对糖尿病性PAD的影响及其潜在机制。
通过结扎db/db小鼠股动脉建立糖尿病性PAD动物模型。采用激光多普勒成像和微型计算机断层扫描（micro-CT）评估血流恢复和动脉生成情况。使用组织病理学、蛋白质印迹分析、酶联免疫吸附测定和实时聚合酶链反应测定评估与动脉生成和细胞焦亡相关的内皮细胞功能。将人血管内皮细胞（HUVECs）和人血管平滑肌细胞（VSMCs）用通心络预处理4小时，然后在高糖和缺氧条件下孵育以诱导细胞损伤。然后，测量HUVEC焦亡和功能、HUVEC-VSMC相互作用以及VSMC迁移的指标。
激光多普勒成像和micro-CT显示，通心络恢复了后肢血流并增强了动脉生成。通心络还抑制内皮细胞焦亡——活性氧/核苷酸结合寡聚化结构域样受体家族含pyrin结构域3/半胱天冬酶-1/GSDMD信号通路。此外，通心络恢复了内皮细胞功能，包括维持血管舒张平衡、作为屏障减轻炎症以及通过Jagged-1/Notch-1/ Ephrin-B2信号通路增强内皮-平滑肌细胞相互作用。在……中观察到了类似结果。
通心络在治疗糖尿病性PAD中具有促动脉生成作用，其机制可能与抑制内皮细胞焦亡、恢复内皮细胞功能以及促进内皮细胞-平滑肌细胞相互作用有关。
