Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease  

作　　者：Jiao-Jiao Gu Yun-Long Hou Yi-Hui Yan Jie Li Ya-Ru Wei Kun Ma Xiao-Qi Wang Jie-Han Zhang Dan-Dong Wang Cui-Ru Li Dong-Qi Li Ling-Ling Sun Huai-Lin Gao 

机构地区：[1]Graduate School,Hebei University of Chinese Medicine,Shijiazhuang 050090,Hebei Province,China [2]Graduate School,Hebei Medical University,Shijiazhuang 050011,Hebei Province,China [3]Graduate school,Hebei Yiling Pharmaceutical Research Institute,Shijiazhuang 050035,Hebei Province,China [4]Graduate school,Henan University of Traditional Chinese Medicine,Shijiazhuang 450000,Hebei Province,China

出　　处：《World Journal of Diabetes》2023年第3期234-254,共21页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by The Hebei Province Natural Science Foundation,No. H2019106062;Key R&D Plan of Hebei Provincial Department of Science and Technology,No. 223777155D;Research Project of Hebei Provincial Administration of Traditional Chinese Medicine,No. 2023179

摘　　要：BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability 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.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS 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 immunosorbent assay and real-time polymerase chain reaction assays.In vitro,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,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via 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 in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of end

关 键 词：Diabetic peripheral arterial disease ARTERIOGENESIS Endothelial cell Inflammation PYROPTOSIS 

分 类 号：R587.2[医药卫生—内分泌]