藏族脐带间充质干细胞外泌体在低氧性肺动脉高压治疗中的作用及其机制研究

干细胞及其外泌体已成为肺动脉高压细胞治疗的研究热点。前期研究结果发现，藏族对低氧环境具有独特的遗传适应机制和最佳适应能力，因此其间充质干细胞在低氧病理微环境中发挥的治疗作用可能有着一定优势。基于此，本课题拟采取青藏高原世居健康藏族和移居汉族新生儿脐带，原代分离培养和鉴定脐带间充质干细胞（UCMSCs）并提取其外泌体，首先进行生物学特性和高通量miRNA测序的比较分析；然后在低压氧舱内构建低氧性肺动脉高压（HPH）动物模型，并给予两组人群UCMSCs外泌体干预后观察其疗效；最后在细胞水平上，分别对低氧诱导的人肺动脉内皮细胞及肺动脉平滑肌细胞进行UCMSCs外泌体干预，进一步观察藏族UCMSCs外泌体对低氧诱导的人肺动脉内皮细胞间质化及肺动脉平滑肌细胞增殖的影响，以期阐明藏族UCMSCs外泌体在HPH肺血管重建中的治疗作用并探讨其可能的机制，从而为今后HPH的干细胞外泌体治疗提供理论依据。

Stem cells and their exosomes have become a hot topic in the treatment of pulmonary artery hypertension cells. Our previous research results showed that Tibetan have their unique genetic adaptation mechanism and best adaptability to hypoxic environment. So the therapeutic effect of their mesenchymal stem cells in hypoxic pathological microenvironment may have some advantages. Base on this, this project plan to use the umbilical cord of healthy Tibetan and immigrated Han nationalities living in the Qinghai Tibet Plateau to carry out the primary isolation, culture and identification of umbilical cord mesenchymal stem cells (UCMSCs), and extract its exosomes. Firstly, the comparative analysis of biological characteristics and high-throughput miRNA sequencing will be carried out. Then, the HPH animal models will be constructed in the hypobaric oxygen chamber, and the therapeutic effects of umbilical cord mesenchymal stem cells-derived exosomes of the two groups are observed after intervention through caudal vein injection. Finally, at the cell level, the human pulmonary vascular endothelial cells and pulmonary artery smooth muscle cells are intervened by Tibetan umbilical cord mesenchymal stem cells-derived exosomes, and the effects of umbilical cord mesenchymal stem cells-derived exosomes on hypoxia induced pulmonary vascular endothelial cells endothelial-to-mesenchymal transition and smooth muscle cell proliferation will be further observed. The purpose of this study is to clarify the therapeutic effect of Tibetan umbilical cord mesenchymal stem cells-derived exosomes in HPH treatment and to explore the possible mechanism, so as to provide a theoretical basis for stem cell therapy of HPH in the future.