新生儿缺血缺氧性脑病（NHIE）引起新生儿死亡或长期神经功能障碍，是临床面临的重大问题。神经自噬性损伤是NHIE发生的重要因素之一，抑制神经自噬性损伤可望成为NHIE治疗的有效手段。申请人前期研究显示，骨髓间充质干细胞（BMSCs）治疗可降低自噬减轻NHIE神经损伤；RNA-seq检测发现NHIE后神经元中SYNPO2增高，且BMSCs治疗降低SYNPO2表达，结合文献报道SYNPO2参与自噬体形成并调控骨骼肌自噬，提示SYNPO2可能通过自噬参与BMSCs修复NHIE。据此，本项目拟从动物、细胞和分子水平进一步探讨①BMSCs是否通过抑制神经自噬减轻NHIE损伤；②SYNPO2参与NHIE中神经自噬性损伤的功能；③BMSCs是否通过下调SYNPO2降低神经自噬性损伤发挥治疗NHIE的作用机制。以上问题的解决将为NHIE研究提供新靶点，为BMSCs在NHIE的临床应用提供科学依据。

Neonatal hypoxic-ischemic encephalopathy (NHIE), representing the major cause of neonatal death or long-term neurodevelopmental disabilities, has been a major practical problem currently faced by the clinic. It has been shown that autophagic nerve injury is one of the important factors in the occurrence of NHIE, and inhibition of autophagic nerve injury is expected to be an effective treatment for NHIE. As our previous studies revealed, bone marrow mesenchymal stem cells (BMSCs) treatment could reduce autophagy to attenuate the nerve injury induced by NHIE; the SYNPO2 expression exhibited an increase in NHIE brain tissues, which was decreased in the treatment of BMSCs demonstrated by RNA-seq detection. Evidence showed that SYNPO2 is involved in the autophagosome formation, thus regulates autophagy of skeletal muscle, indicating that SYNPO2 plays a role in BMSCs repairing NHIE through autophagy. Therefore, this study intends to verify whether BMSCs could ameliorate NHIE injury by inhibiting nerve autophagy; Moreover, to clarify the role of SYNPO2 in promoting autophagic nerve injury as well as the mechanisms of BMSCs alleviating NHIE based on SYNPO2 down-regulation in rats, cells and molecular levels. The solution of the above problems will provide a new target for NHIE research and provide a scientific basis for the clinical application of BMSCs in NHIE.