SDF-1/CXCR4轴调控内源性干细胞动员在电针治疗心肌梗死中的作用机制

Cardiovascular disease has become one of the major diseases that threaten human health, especially myocardial infarction (MI). The clinical effect of electroacupuncture on myocardial protection has been gradually confirmed. However, the mechanism of effect of electroacupuncture on MI is not yet clear. SDF-l/CXCR4 axis plays an important role in tissue ischemia and myocardial regeneration, and this axis is the key signal for stem cells homing to ischemic myocardium. The aim of this project is to investigate whether SDF-1/CXCR4 axis regulation of endogenous stem cell mobilization is involved in electroacupuncture for myocardial protection. The model of MI is established by ligating the left anterior descending coronary artery and the effect of electroacupuncture on the migration and homing of endogenous stem cells after MI will be observed after electroacupuncture treatment at acupoints "Neiguan" and "Xinyu". The role of electroacupuncture on bone marrow stem cell mobilization is further clarified through GFP and c-kit double immunofluorescence labeling and flow cytometry analysis of peripheral blood using GFP-positive bone marrow transplantation model after MI. And the mechanism of electroacupuncture regulating SDF-1/CXCR4 axis on stem cell homing and myocardial regeneration will be explored via CXCR4 knockout mice. This study will expand the understanding of the mechanism of mobilization of endogenous stem cells after MI, explore the specific therapeutic target for MI as well as provide theoretical and experimental basis for prevention and treatment of MI by acupuncture and moxibustion.

心血管疾病是威胁人类健康的重大疾病之一，尤其是心肌梗死。电针对心肌保护的临床效果已逐渐被证实。然而，电针防治心肌梗死的作用机制尚不明确。SDF-l/CXCR4轴在组织缺血损伤和心肌再生修复中发挥重要作用，是干细胞有效归巢到缺血心肌的关键信号轴。本项目旨在探讨电针是否通过SDF-1/CXCR4轴调控内源性干细胞动员参与心肌保护。通过结扎左冠状动脉前降支建立心肌梗死模型，采用电针“内关”和“心俞”穴进行治疗，观察电针对心肌梗死后内源性干细胞动员的影响；采用GFP+骨髓移植小鼠，通过GFP和c-kit免疫荧光双标和外周血流式细胞仪分析，进一步明确电针对骨髓干细胞动员的作用。并通过CXCR4敲除小鼠深入探讨电针调控SDF-1/CXCR4 轴在干细胞动员及心肌再生中的作用机制。本研究将拓展对心肌梗死后内源性干细胞动员调控机制的认识，探索心肌梗死的特异性治疗靶点，为针灸防治心肌梗死提供理论和实验基础。

心肌梗死是威胁人类健康的重大疾病之一，电针对心肌保护的临床效果已逐渐被证实，但电针防治心肌梗死的作用机制尚不明确。本项目通过结扎左冠状动脉前降支建立心肌梗死模型，采用电针“内关”和“心俞”穴进行治疗，利用超声心动图、免疫组化、ELISA、RT-qPCR、Western blot、流式细胞术等方法，观察电针对心肌梗死面积、胶原沉积、血管新生、心肌组织细胞凋亡和增殖的影响以及电针对心肌梗死后内源性干细胞和骨髓干细胞动员的影响；通过构建CXCR4+/-基因敲除小鼠深入探讨电针调控SDF-1/CXCR4 轴在干细胞动员及心肌再生中的作用机制。结果显示，电针能够改善心肌梗死后局部的微环境，促进梗死区域血管新生，减少梗死面积以及梗死区胶原沉积，从而改善心肌梗死大鼠的心功能；通过检测心脏及外周血中干细胞，证明了电针能够在心肌梗死后动员内源性干细胞和骨髓干细胞，其机制可能与SDF-1/CXCR4轴介导的干细胞动员有关；本项目还通过非靶向代谢组学，分析电针对心肌梗死后代谢差异物和代谢通路的影响，结果显示，电针能影响牛磺酸和亚牛磺酸以及色氨酸的代谢通路，提示电针可能通过调控以上代谢通路实现对心肌的保护作用。本项目为临床推广电针早期介入治疗心肌梗死提供了实验和理论依据。