基于外泌体miR-210调控低氧-糖酵解促血管新生机制研究益肾活血方抗肾纤维化效应

肾间质纤维化（RIF）是所有慢性肾脏病发展至终末期最后的共同通路。目前认为，肾周毛细血管网（PTC）损伤是导致RIF发生、发展的关键因素之一。经前期研究证实：中药益肾活血方通过miR-126/VEGF/Notch通路发挥促血管新生和抗RIF作用。结合前期研究工作和外泌体来源microRNA参与调控低氧-糖酵解-血管新生这一重要发现，我们提出假说：益肾活血方通过外泌体miR-210/HIF-1α/PFKFB3信号途径，干预内皮细胞低氧损伤和能量代谢障碍，进而发挥促血管新生和抗RIF效应。本研究以UUO大鼠作为实验动物模型，同时建立体外类缺血/缺氧HUVECs培养体系，旨在从外泌体-microRNA-内皮细胞不同层次深入研究中药复方抗RIF新机制，不仅为探索低氧-能量代谢-肾纤维三者关系提供重要实验依据，并且对系统阐释慢性肾脏病“久病入络”的微观实质亦具有重要的理论价值。

Renal interstitial fibrosis (RIF) is the last common pathway for the development of all chronic kidney diseases(CKD) to the end stage. The damage of periglomerular capillary network (PTC) is considered to be one of the key factors leading to the occurrence and development of RIF. Proximal studies confirmed that traditional Chinese medicine Yishen Huoxue prescription promote angiogenesis and anti RIF through the miR-126/VEGF/Notch pathway. Based on the previous work and the important fact that the exosomes derived microRNA involved in the regulation of hypoxia-energy metabolism disorder-endothelial injury repair, we hypothesized that yishen huoxue prescription promoting angiogenesis and anti renal fibrosis by interferes with endothelial cells hypoxia injury and energy metabolism disorder through exosomes derived miR-210 acting on the HIF-1α/PFKFB3 signaling pathway. The UUO rat was used as an experimental animal model and an in vitro ischemia/hypoxia HUVECs culture system was established. The aim of this study is to explore the new mechanism of anti RIF with traditional Chinese medicine compound from different levels of exosomes- microRNA- endothelial cells.Through the implementation of the project,it not only provides an important experimental basis for the systematic interpretation of the close relationship between hypoxia-energy metabolism and RIF, but also has important theoretical value for further exploring the microscopic essence of collaterals disorders due to the long illness in CKD.