补肾活血方调控VEGF-C/VEGFR-3信号促进淋巴管成熟和功能对骨性关节炎的影响

项目名称： 补肾活血方调控VEGF-C/VEGFR-3信号促进淋巴管成熟和功能对骨性关节炎的影响

项目编号： No.81673782

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 石继祥

作者单位： 上海中医药大学

项目金额： 25万元

中文摘要： 骨性关节炎（OA）致关节破坏，功能障碍，甚则残疾。现无有效治疗。我们前期研究发现：淋巴管成熟与功能与OA病理过程密切相关，OA关节周围成熟淋巴管减少、清除功能下降(Shi J, et al. Arthritis Rheumatol.2014)，致炎性物质堆积，关节水肿，软骨及骨破坏；而补肾活血方可显著减轻OA关节肿痛，增加VEGF-C表达，其机制仍不清楚。据此我们假设，补肾活血方可调控VEGF-C/VEGFR-3信号促进淋巴管成熟与功能，加快炎性物质清除，缓解炎症，减轻关节损伤。本研究拟利用半月板韧带损伤OA模式小鼠及其淋巴管平滑肌细胞，采用全切片成像系统（WSIS）淋巴管定量技术、近红外线-吲哚菁绿（NIR-ICG）淋巴功能检测技术和细胞学，分子生物学等技术，从VEGF-C/VEGFR-3通路，探索“补肾活血”中药调控淋巴管增生与功能对OA炎症程度及转归的影响，为临床治疗OA提供证据。

中文关键词： 骨性关节炎；补肾活血方；VEGF-C/VEGFR-3；信号通路；淋巴管平滑肌细胞；淋巴管成熟

英文摘要： Osteoarthritis (OA) induces destruction and dysfunction of joints, or even extremity disability，and has no cure so far. In our previous studies, we found that there are close relationships between the maturation and function of lymphatic vessels and the pathological process of osteoarthritis. In and around the OA joints, there are accumulation of inflammatory substances, arthroedema, and destruction of articular cartilage and subchondral bone, accompanying with the reduction of mature lymphatic vessels and decrease of lymphatic clearance (Shi J, et al. Arthritis Rheumatol. 2014); with the use of BushenHuoxue decoction in OA patients and mice, the joint swelling and pain could be alleviated, and joint inflammation reduced, with vascular endothelial growth factor-C (VEGF-C) expression improved, but the mechanism is still unknown. We hypothesize that BushenHuoxue decoction promote the lymphatic maturation and function via regulation the VEGF-C/VEGFR-3 signaling which can accelerate the clearance of inflammatory substances and clastic enzymes to relieve inflammation and joint damage on OA. By using lymphatic function detection techniques such as whole-slide imaging system (WSIS), indocyanine green near-infrared (ICG-NIR), and cytology and biology techniques in meniscal-ligamentous injury OA (MLI-OA) models and lymphatic smooth muscle cells（LSMC）, from the VEGF-C/VEGFR-3 pathway, we will try to find out the effects of the BushenHuoxue decoction regulation the lymphatic maturation and function on joint inflammation and prognosis in osteoarthritic mice and cells, which to provide evidence for clinical treatment of OA.

英文关键词： Osteoarthritis;BuShenHuoXue decoction;VEGF-C/VEGFR-3 signaling;Lymphatic smooth muscle cell;Lymphatic maturation