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乌梢蛇II型胶原蛋白调节胶原诱导性关节炎小鼠中Treg/Th17细胞的平衡。

Zaocys type II collagen regulates the balance of Treg/Th17 cells in mice with collagen-induced arthritis.

作者信息

Wang Hao, Feng Zhitao, Zhu Junqing, Chen Xiaoguang, Wu Xianghui, Li Juan

机构信息

Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong; and Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.

Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.

出版信息

Clin Exp Rheumatol. 2017 May-Jun;35(3):452-461. Epub 2016 Dec 28.

Abstract

OBJECTIVES

Zaocys type II collagen is an active collagen extracted from Zaocys that has been used to treat rheumatoid arthritis in China for over 1000 years. However, the mechanism still remains unknown. Therefore, we set out to investigate the inhibitory effect and possible mechanism of action of zaocys type II collagen on collagen-induced arthritis.

METHODS

Collagen-induced arthritis was induced in C57BL/6 mice by immunisation with type II collagen. After immunisation, the mice were treated with Zaocys type II collagen. Clinical and histological scores were assessed and the cytokine levels in the serum and lymphocytes supernatant from the spleen and mesenteric lymph node were determined by enzyme-linked immune sorbent assay. The T-helper 17 cell and regulatory-T cell frequencies were analysed by flow cytometry and the expression of interest markers was examined by direct immuno-fluorescence.

RESULTS

The arthritis score and severity of histological inflammation and cartilage destruction were dose-dependently reduced after treatment. The analysis results indicated that Zaocys type II collagen significantly increased the proportion of regulatory-T cells and lowered the T-helper 17 cells, it also increased the number of regulatory-T cells and conversely decreased the T-helper 17 cells in synovial tissue compared with the model group. Treatment also caused a higher level of transforming growth factor-β and a decreased production of interleukin -17A.

CONCLUSIONS

The oral administration of Zaocys type II collagen potently suppressed the severity of collagen-induced arthritis by repairing the imbalance between regulatory-T cells and T-helper 17 cells, suggesting that it might be a promising candidate for the treatment of rheumatoid arthritis.

摘要

目的

蕲蛇Ⅱ型胶原是从蕲蛇中提取的一种活性胶原,在中国用于治疗类风湿关节炎已有1000多年历史。然而,其作用机制仍不清楚。因此,我们着手研究蕲蛇Ⅱ型胶原对胶原诱导性关节炎的抑制作用及其可能的作用机制。

方法

用Ⅱ型胶原免疫C57BL/6小鼠诱导胶原诱导性关节炎。免疫后,用蕲蛇Ⅱ型胶原治疗小鼠。评估临床和组织学评分,并通过酶联免疫吸附测定法测定血清以及脾脏和肠系膜淋巴结淋巴细胞上清液中的细胞因子水平。通过流式细胞术分析辅助性T细胞17和调节性T细胞的频率,并通过直接免疫荧光检查相关标志物的表达。

结果

治疗后,关节炎评分以及组织学炎症和软骨破坏的严重程度呈剂量依赖性降低。分析结果表明,与模型组相比,蕲蛇Ⅱ型胶原显著增加了调节性T细胞的比例,降低了辅助性T细胞17的比例,还增加了滑膜组织中调节性T细胞的数量,反之减少了辅助性T细胞17的数量。治疗还使转化生长因子-β水平升高,白细胞介素-17A的产生减少。

结论

口服蕲蛇Ⅱ型胶原通过修复调节性T细胞和辅助性T细胞17之间的失衡,有效抑制了胶原诱导性关节炎的严重程度,表明它可能是治疗类风湿关节炎的一个有前景的候选药物。

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