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 ...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 endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.展开更多
Diabetic foot ulcers(DFUs)have become one of the important causes of mortality and morbidity in patients with diabetes,and they are also a common cause of hospitalization,which places a heavy burden on patients and so...Diabetic foot ulcers(DFUs)have become one of the important causes of mortality and morbidity in patients with diabetes,and they are also a common cause of hospitalization,which places a heavy burden on patients and society.The prevention and treatment of DFUs requires multidisciplinary management.By controlling various risk factors,such as blood glucose levels,blood pressure,lipid levels and smoking cessation,local management of DFUs should be strengthened,such as debridement,dressing,revascularization,stem cell decompression and oxygen therapy.If necessary,systemic anti-infection treatment should be administered.We reviewed the progress in the clinical practice of treating DFUs in recent years,such as revascularization,wound repair,offloading,stem cell transplantation,and anti-infection treatment.We also summarized and prospectively analyzed some new technologies and measurements used in the treatment of DFUs and noted the future challenges and directions for the development of DFU treatments.展开更多
基金Supported by The Hebei Province Natural Science Foundation,No. H2019106062Key R&D Plan of Hebei Provincial Department of Science and Technology,No. 223777155DResearch Project of Hebei Provincial Administration of Traditional Chinese Medicine,No. 2023179
文摘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 endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.
基金Supported by Chongqing Science and Technology Bureau and Health Commission of Chinese Medicine Technology Innovation and Application Development Project,No. 2020ZY013540General Project of Graduate Education and Teaching Reform of Chongqing University,No. cquyjg20329Science and Health Joint Project of Dazu District Science and Technology Bureau,No. DZKJ,2022CCC1001。
文摘Diabetic foot ulcers(DFUs)have become one of the important causes of mortality and morbidity in patients with diabetes,and they are also a common cause of hospitalization,which places a heavy burden on patients and society.The prevention and treatment of DFUs requires multidisciplinary management.By controlling various risk factors,such as blood glucose levels,blood pressure,lipid levels and smoking cessation,local management of DFUs should be strengthened,such as debridement,dressing,revascularization,stem cell decompression and oxygen therapy.If necessary,systemic anti-infection treatment should be administered.We reviewed the progress in the clinical practice of treating DFUs in recent years,such as revascularization,wound repair,offloading,stem cell transplantation,and anti-infection treatment.We also summarized and prospectively analyzed some new technologies and measurements used in the treatment of DFUs and noted the future challenges and directions for the development of DFU treatments.