光动力治疗骨性关节炎的机理研究

Osteoarthritis is a common chronic and disabling disease. The main feature is the degeneration of articular cartilage caused by many factors and the pathogenesis is not clear. The studies recently indicated that the pathogenesis may be related to the cell aging, apoptosis, intra-articular local inflammatory factors and stress. There are no better non-surgical minimally invasive treatments till now. The method, which was based on laser therapy, has unique advantages in selectively killing pathological tissues, easy operation and small trauma. In this project, we are going to investigate the photodynamic therapy on osteoarthritis of animal models based on chosen the animal models and set up the vivo and vitro experimental samples. Then the photodynamic therapy will be taken with the selections of the photosensitizer, the excitation wavelength, the approaches of radiation and drug delivery, and the optimization of the parameters of photodynamic dosimetry. Meanwhile, the mechanism of the dynamic treatment to the osteoarthritis of animal model will be explored using the method of detecting the inflammatory factors (Visfatin, IL-6, etc.), analysing the changes of joint function and pathological changes of the synovial cells by observing the X-rays of joint. The investigation can provide a theoretical and experimental basis for clinical treatment.

骨性关节炎（osteoarthritis，OA）是一种常见的由多种因素引起的以关节软骨的退行性变为主要特征的慢性进行性致残性疾病，其发病机制尚不明确，研究认为可能与细胞老化、细胞凋亡、关节内局部炎症因子和压力机制等有关。目前，尚无较好的非手术微创性治疗方法。光动力疗法是在激光治疗学基础上发展起来的一种能诱导细胞坏死和凋亡的微创性治疗手段，能够选择性杀伤病理组织，治疗方法简便，创伤性小，有其独特的优势。本项目拟骨性关节炎动物模型基础上，分体内实验组和体外实验组，选择适当的光敏剂和有效的激发光波长对骨性关节炎动物模型进行光动力治疗，对所涉及到的光照方式，给药方式，光动力剂量学等参数进行优化选择，使之达到最佳治疗效果，同时，检测炎性因子(Visfatin、IL-6等)、观察关节X片和关节功能的改变以及关节处病变组织的病理变化情况，对光动力治疗骨关节炎动物模型的机理进行研究，为临床治疗提供依据。

骨性关节炎(Osteoarthritis, OA)最主要的病理改变为关节软骨病损，同时炎症滑膜细胞的浸润、增生及各种炎性细胞因子的分泌，又会进一步造成骨与软骨的破坏。光动力疗法可以通过多种方式实现对病变组织的破坏，并且诱导宿主细胞产生抗免疫应答。光动力疗法将成为骨性关节炎治疗的一个新方向。. 本项目开展了一系列关于光动力疗法治疗早期类风湿性关节炎(rheumatoid arthritis，RA)和早期骨性关节炎的动物实验研究。实验结果发现，光动力疗法能选择性地杀死RA大鼠增生的滑膜细胞，减少血管翳的形成，也抑制了RA发病过程中炎性细胞因子的表达。光动力疗法可以使早期OA大鼠增生的炎症滑膜细胞坏死或凋亡，延缓软骨的血管侵入；诱导宿主细胞产生抗免疫应答，减弱炎症反应、延缓软骨细胞的损伤，促进软骨组织的修复。光动力疗法可以下调OA家兔模型血清中软骨分解代谢标记物的水平，有效减缓软骨的降解，刺激软骨再生。项目中设计了一种关节腔注射光敏剂联合光纤关节腔内照射的实验手段，并且发现，关节腔内照射光动力治疗相较于关节腔外照射光动力治疗，不仅在下调关节软骨分解代谢标记物水平以及减缓软骨的降解、刺激软骨再生等方面上表现出更好的效果，而且更加稳定。通过上述实验总结了光动力疗法治疗骨性关节炎的过程中疗效较好的给药方式，光照方式以及光动力剂量。