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ALA 诱导的滑膜组织卟啉形成和荧光:体内外研究。

ALA-induced porphyrin formation and fluorescence in synovitis tissue In-vitro and in vivo studies.

机构信息

Department of Orthopedic Surgery, National Hospital, Oslo, Norway; Department of Radiation Biology, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.

Department of Radiation Biology, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.

出版信息

Photodiagnosis Photodyn Ther. 2005 Dec;2(4):299-307. doi: 10.1016/S1572-1000(05)00107-9. Epub 2005 Nov 11.

DOI:10.1016/S1572-1000(05)00107-9
PMID:25048871
Abstract

The synovial inflammatory process in rheumatoid arthritis (RA) is accompanied by massive tumor-like proliferation and activation of the connective stroma. These abnormal cells actively invade and destroy the peri-articular bone and cartilage at the margins of joints where synovium and bone are attached. There is still a lack of minimally invasive synovectomy methods, which might be suitable for the smaller joints. Unfortunately, these joints are usually involved in the disease. Photodynamic therapy has been evaluated as a possible treatment modality for RA synovitis. The present study describes the differences of 5-aminolevulinic acid (5-ALA) and 5-ALA ester-induced protoporphyrin IX (PpIX) production in cell cultures obtained from patients with RA, osteoarthritis (OA) and human sarcoma cell line (HS 192.T) and in a collagen-induced arthritis model in rats. The incubation of cells with hexyl aminolevulinate (HAL) induced the same amount of fluorescence as 5-ALA and methyl aminolevulinate (MAL) at about a 100-fold lower concentration. Incubation with HAL-induced accumulation of at least twice as much porphyrins in RA- and HS 192.T-cells than 5-ALA and MAL in OA-cells. Similar levels of porphyrins were accumulated in RA and the malignant cells. In vivo, intra-articular application of 5-ALA induced a significant porphyrin accumulation in synovitis tissue as measured by in situ fluorescence spectroscopy. In contrast to our in vitro results and other reports, we could not detect enhanced fluorescence after application of up to 0.1mg HAL.

摘要

类风湿关节炎 (RA) 的滑膜炎症过程伴随着大量肿瘤样增殖和结缔组织基质的激活。这些异常细胞积极侵袭和破坏关节边缘附着滑膜和骨的周围骨和软骨。目前仍然缺乏适用于较小关节的微创滑膜切除术方法。不幸的是,这些关节通常会受到疾病的影响。光动力疗法已被评估为治疗 RA 滑膜炎的一种可能方法。本研究描述了从 RA 患者、骨关节炎 (OA) 患者和人肉瘤细胞系 (HS 192.T) 获得的细胞培养物以及胶原诱导性关节炎大鼠模型中,5-氨基酮戊酸 (5-ALA) 和 5-ALA 酯诱导的原卟啉 IX (PpIX) 产生的差异。用己基氨基酮戊酸 (HAL) 孵育细胞可诱导与 5-ALA 和甲氨基酮戊酸 (MAL) 相同的荧光,浓度低约 100 倍。用 HAL 孵育可使 RA 和 HS 192.T 细胞中的卟啉积累至少增加两倍,而在 OA 细胞中则增加两倍。RA 和恶性细胞中积累了相似水平的卟啉。在体内,通过原位荧光光谱测量,关节内应用 5-ALA 可诱导滑膜炎症组织中卟啉的显著积累。与我们的体外结果和其他报告相反,我们在应用高达 0.1mg HAL 后未检测到增强的荧光。

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