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依托考昔可预防大鼠反复关节内注射尿酸钠诱导的痛风性关节炎中骨质溶解的进展。

Etoricoxib prevents progression of osteolysis in repeated intra-articular monosodium urate-induced gouty arthritis in rats.

作者信息

Lin Yen-You, Jean Yen-Hsuan, Lin Sung-Chun, Feng Chien-Wei, Kuo Hsiao-Mei, Lai Yu-Cheng, Kuo Tsu-Jen, Chen Nan-Fu, Lee Hsin-Pai, Wen Zhi-Hong

机构信息

Department of Sports Medicine, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan.

Department of Orthopedic Surgery, Pingtung Christian Hospital, Pingtung, No. 60, Dalian Road, Pingtung 90059, Taiwan.

出版信息

J Adv Res. 2020 Feb 29;24:109-120. doi: 10.1016/j.jare.2020.02.014. eCollection 2020 Jul.

Abstract

Deposition of monosodium urate (MSU) crystals in the joint or synovium is the major factor in Gouty arthritis (GA). The clinical features of chronic and recurrent GA include pain and the subsequent development of chronic tophaceous GA with multiple tophi deposits accompanied by osteolysis. The majority of previous animal studies have focused on MSU-induced acute GA without making observations regarding osteolysis. In the study, intra-articular injections of MSU into the knee (2 times/week for 10 weeks) was used to induce chronic and recurrent attacks of GA that in turn induced progressive osteolysis. Moreover, we also evaluated whether the clinical, nonsteroidal anti-inflammatory drug (NSAID) etoricoxib attenuated the osteoclastogenesis of progressive osteolysis. The knee morphometry and the expression of osteoclastogenesis-related proteins (cathepsin K and matrix metalloproteinase-9 and -13) in the knee were examined by micro-CT and immunohistochemistry, respectively. Results showed that oral etoricoxib not only significantly attenuated the nociceptive behaviors of the rats but that it also inhibited the expression of osteoclastogenesis-related proteins in their knee joints in chronic and recurrent attacks of GA. Our findings thus suggest that NSAIDs not only inhibit nociception but also prevent the progression of osteolysis in chronic and repeated attacks of GA.

摘要

尿酸单钠(MSU)晶体在关节或滑膜中的沉积是痛风性关节炎(GA)的主要因素。慢性复发性GA的临床特征包括疼痛以及随后发展为伴有多个痛风石沉积和骨质溶解的慢性痛风石性GA。以前的大多数动物研究都集中在MSU诱导的急性GA上,而没有对骨质溶解进行观察。在本研究中,通过向膝关节内注射MSU(每周2次,共10周)来诱导GA的慢性复发性发作,进而诱导进行性骨质溶解。此外,我们还评估了临床使用的非甾体抗炎药(NSAID)依托考昔是否能减轻进行性骨质溶解的破骨细胞生成。分别通过显微CT和免疫组织化学检查膝关节形态以及膝关节中破骨细胞生成相关蛋白(组织蛋白酶K、基质金属蛋白酶-9和-13)的表达。结果表明,口服依托考昔不仅能显著减轻大鼠的伤害感受行为,还能抑制GA慢性复发性发作时其膝关节中破骨细胞生成相关蛋白的表达。因此,我们的研究结果表明,NSAIDs不仅能抑制伤害感受,还能防止GA慢性反复发时骨质溶解的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4699/7114632/e367753c4a29/ga1.jpg

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