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目的比较关节腔内照射光动力疗法与关节腔外照射光动力疗法对骨性关节炎治疗效果的差异。方法日本大耳白兔20只,随机分为4组,分别为空白对照组、模型对照组、关节腔内照射光动力治疗组(internal photodynamic therapy group,IN-PDT)以及关节腔外照射光动力治疗组(external photodynamic therapy group,EX-PDT),每组各5只。除空白对照组外,其余各组均施以改良Hulth方法建立骨性关节炎动物模型。造模8周后,采用关节腔注射光敏剂后结合光动力疗法,其中IN-PDT组和EX-PDT分别采用关节腔内照射和关节腔外照射的方案进行治疗。采用HE染色观察软骨形态结构的变化,采用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清中COMP、YKL-40及Ⅱ型胶原羧基端端肽(Carboxy-Terminal Telepeptides of TypeⅡCollagen,CTX-Ⅱ)水平的变化,并对实验结果进行统计学分析。结果 (1)HE染色:光镜下观察到,相较于模型组两个治疗组的关节软骨组织结构及软骨细胞形态均有所恢复,且IN-PDT组疗效优于EX-PDT组。(2)关节软骨组织损伤Mankin’s评分:对比模型组,两个治疗组评分均有降低,且IN-PDT组评分小于EX-PDT组。(3)ELISA检测:两治疗组的血清COMP、YKL-40、CTX-Ⅱ水平的均值均小于模型组,并且IN-PDT组三种标记物水平的均值亦分别低于EX-PDT组(P<0.05)。结论关节腔内照射的光动力疗法与关节腔外照射的光动力疗法均可以恢复关节软骨组织结构,封闭新生血管,抑制软骨的过度分解,延缓骨性关节炎的病理进程。其中,关节腔内照射的疗效及稳定性明显优于关节腔外照射的光动力疗法。
Objective To compare the therapeutic effect of intra-articular photodynamic therapy and articular cavity external beam photodynamic therapy on osteoarthritis. Methods Twenty Japanese white rabbits were randomly divided into 4 groups: blank control group, model control group, intra-articular photodynamic therapy group (IN-PDT), and extra-articular photodynamic therapy Treatment group (external photodynamic therapy group, EX-PDT), 5 in each group. Except the blank control group, all the other groups were given the modified Hulth method to establish the animal model of osteoarthritis. After 8 weeks of modeling, the rats were treated with intra-articular injection of photosensitizer and photodynamic therapy. The IN-PDT group and EX-PDT were treated with intra-articular and extra-articular irradiation respectively. The morphological changes of cartilage were observed by HE staining. The levels of COMP, YKL-40 and type II Collagen carboxyterminal peptide in serum were detected by ELISA (enzyme linked immunosorbent assay) Ⅱ) level changes, and the experimental results were statistically analyzed. Results (1) HE staining: Under the light microscope, compared with the model group, the articular cartilage structure and cartilage morphology of the two treatment groups recovered, and the IN-PDT group was superior to the EX-PDT group. (2) Mankin’s score of articular cartilage tissue injury: Compared with the model group, the score of the two treatment groups decreased and the score of IN-PDT group was smaller than that of EX-PDT group. (3) The serum levels of COMP, YKL-40 and CTX-II in the two treatment groups were lower than those in the untreated group by ELISA. Mean values of the three markers in the IN-PDT group were also lower than those in the EX-PDT group <0.05). Conclusion Photodynamic therapy of intra-articular irradiation and photodynamic therapy of extra-articular irradiation can restore the structure of articular cartilage, occlude new blood vessels, inhibit the over-decomposition of cartilage and delay the pathological process of osteoarthritis. Among them, the efficacy and stability of intra-articular irradiation was significantly better than that of intra-articular radiotherapy.