Abstract：
Neonatal hypoxic-ischemic encephalopathy (HIE) is an abnormal neurological condition caused by hypoxic-ischemic damage during the perinatal period. Human placenta derived mesenchymal stem cells (hPMSCs) have been shown to have protective and reparative effects in various neurological diseases; however, the research on HIE is insufficient. This study aimed to establish a rat model of HIE and transplant hPMSCs through the lateral ventricle after hypoxic-ishcemic (HI) brain damage to observe its protective effects and mechanisms, with a focus on brain apoptosis compared among groups. Differentially expressed apoptosis-related proteins were screened using a rat cytokine array and subsequent verification. Neuropilin-1 (NRP-1) and Semaphorin 3A (Sema 3A) were selected for further investigation. Western blotting was used to quantify the expression of Sema 3A and the proteins related to PI3K/Akt/mTOR signaling pathway. Exogenous Sema 3A was added to evaluate the effects of Sema 3A/NRP-1 on hPMSCs following HI injury. hPMSCs transplantation ameliorated HI-induced pathological changes, reduced apoptosis, and improved long-term neurological prognosis. Furthermore, Sema 3A/NRP-1 was a key regulator in reducing HI-induced apoptosis after hPMSCs transplantation. hPMSCs inhibited the expression of Sema 3A/NRP-1 and activated the PI3K/Akt/mTOR signaling pathway. Additionally, exogenous Sema 3A abolished the protective effects of hPMSCs against HI. In conclusion, hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis after HI by downregulating Sema 3A/NRP-1 expression and activating the PI3K/Akt/mTOR signaling pathway.
摘要：
新生儿缺氧缺血性脑病（HIE）是围产期缺氧缺血性损伤引起的神经系统异常疾病。人胎盘来源的间充质干细胞（hPMSCs）已被证明在各种神经系统疾病中具有保护和修复作用；然而，对HIE的研究不足。本研究旨在建立大鼠缺氧缺血性脑损伤(HI)后HIE模型并通过侧脑室移植hPMSCs,观察其保护作用及机制。以脑细胞凋亡为重点进行组间比较。使用大鼠细胞因子阵列筛选差异表达的凋亡相关蛋白并随后进行验证。选择神经菌毛蛋白-1(NRP-1)和信号素3A(Sema3A)进行进一步研究。Western印迹用于定量Sema3A和PI3K/Akt/mTOR信号通路相关蛋白的表达。添加外源性Sema3A以评估Sema3A/NRP-1对HI损伤后hPMSCs的影响。hPMSCs移植改善HI诱导的病理变化，减少细胞凋亡，并改善长期神经预后。此外，Sema3A/NRP-1是减少hPMSCs移植后HI诱导的细胞凋亡的关键调节因子。hPMSCs抑制Sema3A/NRP-1的表达并激活PI3K/Akt/mTOR信号通路。此外,外源性Sema3A消除了hPMSCs对HI的保护作用.总之,hPMSCs移植通过下调Sema3A/NRP-1表达和激活PI3K/Akt/mTOR信号通路，减少HI后细胞凋亡并改善长期神经预后。
