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关节腔内注射3'-唾液乳糖对胶原蛋白诱导的类风湿性关节炎小型猪模型的治疗效果

Therapeutic effect of intra-articular injected 3'-sialyllactose on a minipig model of rheumatoid arthritis induced by collagen.

作者信息

Kim Young June, Lee Ju-Young, Yang Mi-Jin, Cho Hyun Jin, Kim Min-Young, Kim Lila, Hwang Jeong Ho

机构信息

Animal Model Research Group, Jeonbuk Branch Institute, Korea Institute of Toxicology, Jeollabukdo, 56212, Republic of Korea.

Pathology Research Group, Jeonbuk Branch Institute, Korea Institute of Toxicology, Jeollabukdo, 56212, Republic of Korea.

出版信息

Lab Anim Res. 2022 Mar 22;38(1):8. doi: 10.1186/s42826-022-00119-2.

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is a chronic inflammatory disease of joint, but there is no known cure. 3'-sialyllactose (3'-SL) is an oligosaccharide that is abundant in breast milk of mammals, and has anti-inflammatory properties. However, the efficacy of 3'-SL on RA remains unclear. The objective of the present study was to evaluate the therapeutic effect of 3'-SL after it was directly injected into the knee joint cavity of a RA minipig model.

RESULTS

Minipig RA model was induced by intra-articular injection of bovine type II collagen emulsified with complete or incomplete Freund's adjuvant into left knee joint. In clinical assessment, lameness and swelling of the hindlimb and increased knee joint width were observed in all animals. After the onset of arthritis, 3'-SL (0, 2, 10, and 50 mg/kg) was directly administered to the left knee joint cavity once a week for 4 weeks. Compared to the vehicle control group, no significant difference in macroscopic observation of the synovial pathology or the expression of inflammation-related genes (IL-1β, TNF-α, and COX2) in the synovial membrane of the knee joint was found. In microscopic observation, cell cloning of the articular cartilage was significantly reduced in proportion to the concentration of 3'-SL administered.

CONCLUSIONS

Our results suggest that intra-articular injected 3'-SL had a therapeutic effect on collagen-induced arthritis at the cellular level with potential as a medication for RA.

摘要

背景

类风湿性关节炎(RA)是一种慢性关节炎症性疾病,但尚无已知的治愈方法。3'-唾液酸乳糖(3'-SL)是一种在哺乳动物母乳中含量丰富的寡糖,具有抗炎特性。然而,3'-SL对RA的疗效仍不清楚。本研究的目的是评估将3'-SL直接注射到RA小型猪模型膝关节腔后的治疗效果。

结果

通过向小型猪左膝关节腔内注射用完全或不完全弗氏佐剂乳化的牛II型胶原诱导建立小型猪RA模型。在临床评估中,所有动物均观察到后肢跛行、肿胀以及膝关节宽度增加。关节炎发作后,每周一次将3'-SL(0、2、10和50mg/kg)直接注入左膝关节腔,持续4周。与载体对照组相比,在滑膜病理学的宏观观察或膝关节滑膜中炎症相关基因(IL-1β、TNF-α和COX2)的表达方面未发现显著差异。在微观观察中,关节软骨的细胞克隆比例与所给予的3'-SL浓度成比例地显著降低。

结论

我们的结果表明,关节腔内注射3'-SL在细胞水平上对胶原诱导的关节炎具有治疗作用,具有作为RA药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/885b/8939226/ed92517cc9b0/42826_2022_119_Fig1_HTML.jpg

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