基于SDF-1/CXCR4信号通路探讨苗药熏蒸对骨性关节炎的作用机制

Osteoarthritis(OA) is a type of chronic and recessive joint disease, among which knee osteoarthritis is the most frequent to see. Angiogenesis plays an important part in the genesis and development of osteoarthritis. In the prophase research, osteoarthritis is found to be closely related to ascular endothelial growth factor(VEGF) which in coordination with SDF-1/CXCR4 signaling pathway can facilitate the angiogenesis of OA while the detailed pathology mechanism still needs to be further studied. Damage to extracellular matrix（ECM）is one of the major mechanisms. Under the induction of SDF-1, VEGF enhances the expression of MMPs in cartilage which breaks the balance between generation and degradation leading to OA . This paper is planned to make an injuried OA model with immobilization of plaster cast by respective experiments on animals and cells. With the help of Western Blot, immunohistochemisty and real-time fluorescent quantiation of PCR, the mechanism of damage was explored in the process of continuing stimulus to cartilage extracellular, which identified the hidden target point and possible mechanism of action of Miao medicine fumigating therapy to OA and bioactive associativity and excretion of associated protein in SDF-1/CXCR4 pathway in order to find the importance of VEGF in the pathway of SDF-1/CXCR. It.is expected to reveal the mechanism of Miao medicine fumigating therapy to extracellular matrix with OA which is about to provide modern and new experimental evidence for Miao medicine curing theory tothe prevention and cure of OA.

骨性关节炎(OA) 是一种慢性、退行性骨关节疾病，以膝关节最为常见。血管新生参与了OA的发生发展，前期研究发现VEGF与OA的发展有密切关系。SDF-1/CXCR4信号通路与VEGF协同促进OA血管新生, 但具体机制尚不完全清楚。ECM破坏是OA中最主要的机制之一，在SDF-1诱导下的VEGF促进软骨细胞MMPs的表达，导致了ECM的产生与降解之间的平衡被打破，从而导致OA的发生。本研究拟通过石膏管型固定制作OA动物模型，以苗医熏蒸作为处理因素，分别采用整体动物实验和组织培养的方法，运用蛋白印记、实时荧光定量PCR等手段，来探索苗医熏蒸干预OA的潜在靶点和SDF-1/CXCR4途径中的相关蛋白的分泌及生物活性的相关性，寻找VEGF在SDF-1/CXCR4途径中的角色，力求达到揭示苗医熏蒸干预OA软骨细胞外损伤作用机制的目的。为古老的苗医熏蒸疗法提供现代实验依据。

骨性关节炎(osteoarthritis,OA) 是一种严重影响人类健康的退行性关节疾病，以膝关节最为常见。骨性关节炎(OA) 是一种慢性、退行性骨关节疾病，以膝关节最为常见。血管新生参与了O A的发生发展，近年来前期研究发现血管新生参与了 OA 的发生发展，VEGF与骨性关节炎OA的发展有密切关系。SDF-1/CXCR4信号通路与VEGF协同促进OA血管新生, 但具体机制尚不完全清楚。ECM破坏是OA中最主要的机制之一，在SDF-1诱导下的VEGF促进软骨细胞MMPs的表达，导致了ECM的产生与降解之间的平衡被打破，从而导致OA的发生。课题组通过4年的工作，主要是从整体动物实验、软骨细胞体外培养及软骨组织体外培养三个方面展开研究，取得了以下实验成果：①通过兔膝关节腔注射碘乙酸钠的方法建立OA模型，确定膝关节腔注射7.5mg/kg 的碘乙酸钠，能够建立早期OA模型；②SDF-1/CXCR4信号轴可能通过激活其下游信号通路增强VEGF的表达，增强血管的通透性，加快炎症的进一步发展，从而加快OA的发展进程；③VEGF的高表达可能会促使基质金属蛋白酶表达升高，又因基质金属蛋白酶可以破坏细胞外基质的动态平衡，降解胶原蛋白及蛋白聚糖，从而加重软骨组织的损伤程度，加快OA的进展；④苗药熏蒸疗法可能通过减少SDF-1的表达，阻断SDF-1与其受体CXCR4结合从而达到抑制VEGF、基质金属蛋白酶（MMP-3、MMP-9、MMP-13）的表达来延缓滑膜炎症，以及降低细胞外基质中II型胶原蛋白及聚集蛋白聚糖的表达来延缓软骨退变，从而达到减缓OA发展进程的作用。⑤培养研究生3名；⑥发表相关学术论文7篇，其中核心3篇，已录用未见刊的5篇；⑦申请国家发明专利2项。