Photodynamic therapy using talaporfin sodium for synovial membrane from rheumatoid arthritis patients and collagen-induced arthritis rats
Photodynamic therapy using talaporfin sodium for synovial membrane from rheumatoid arthritis patients and collagen-induced arthritis rats
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DOI：
10.1007/s10067-007-0794-8
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发表时间：
2008-06-01
影响因子：
3.4
通讯作者：
Nagano, Akira
中科院分区：
文献类型：
--
作者：
Torikai, Eiji;Kageyama, Yasunori;Nagano, Akira
我们研究了使用他拉泊芬钠作为滑膜切除术治疗类风湿关节炎（RA）的新方法的光动力学疗法（PDT）的疗效。我们首先使用RA滑膜（RASM）进行体外和体内研究。RASM来自全膝关节置换术期间的RA患者。在体外研究中，通过荧光显微镜检查从RASM获得的RA成纤维细胞样滑膜细胞（RASC），以测量他拉泊芬钠的细胞内定位。然后对细胞进行PDT，并通过3-（4，5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑鎓内盐测定来检查它们的活力。在体内测定中，如上所述获得RASM，移植到严重联合免疫缺陷（SCID）小鼠上并进行PDT。光动力治疗后第1天，对RASM的损伤面积进行组织学评价。接下来，我们使用患有胶原诱导性关节炎（CIA）的大鼠进行了一项单独的实验。关节内注射他拉泊芬钠后，将CIA滑膜（CIASM）中累积的他拉泊芬钠浓度与软骨、关节周围肌肉和皮肤中的浓度进行比较。然后，我们进行PDT与关节内注射他拉泊芬钠和关节内照射。PDT后1 d测量CIASM损伤面积，PDT后56 d观察踝关节的组织学和放射学变化。在RASM中，他拉泊芬钠在体外溶酶体中蓄积，并且对体外RASC和体内移植到SCID小鼠上的RASM的光毒性依赖于他拉泊芬钠的浓度和激光能量。在CIA大鼠中，他拉泊芬钠在CIASM中的蓄积量大于正常组织。光动力治疗后第1天，CIASM出现选择性损伤，第56天，骨和软骨的破坏得到改善。结论：他拉泊芬钠光动力疗法可能是类风湿关节炎滑膜切除术的一种新方法。
We investigated the efficacy of photodynamic therapy (PDT) using talaporfin sodium as a new method of synovectomy for rheumatoid arthritis (RA). We first used RA synovial membrane (RASM) for in vitro and in vivo study. The RASM was obtained from patients with RA during total knee replacement. In the in vitro study, RA fibroblast-like synoviocytes (RASCs) obtained from the RASM were examined by fluorescent microscopy to measure the intracellular localization of talaporfin sodium. The cells were then subjected to PDT, and their viability was examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium inner salt assay. In the in vivo assay, RASM was obtained as described above, grafted onto severe combined immunodeficiency (SCID) mice and subjected to PDT. The damaged area of RASM was evaluated histologically at 1 day after PDT. Next, we performed a separate experiment using rats with collagen-induced arthritis (CIA). After intra-articular injection of talaporfin sodium, the concentration of talaporfin sodium accumulated in the CIA synovial membrane (CIASM) was compared with that in cartilage, periarticular muscle, and skin. We then performed PDT with intra-articular injection of talaporfin sodium and intra-articular irradiation. The damaged area of the CIASM was measured at 1 day after the PDT, and the articular histological and radiological changes of the ankle were observed at 56 days after the PDT. In RASM, talaporfin sodium accumulated in lysosomes in vitro, and the phototoxicity to RASCs in vitro and to RASM grafted onto SCID mice in vivo depended on the concentration of talaporfin sodium and the laser energy. In CIA rats, there was a greater accumulation of talaporfin sodium in the CIASM than in normal tissue. The CIASM was selectively damaged at 1 day after the PDT, and the bone and cartilage destruction were ameliorated at 56 days after the PDT. In conclusion, PDT using talaporfin sodium might be a new method for synovectomy in patients with RA.