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可溶性与不溶性未变性II型胶原蛋白在改善大鼠骨关节炎方面的差异及其潜在机制。

Differences between soluble and insoluble undenatured type II collagen in improving osteoarthritis in rats and their potential mechanisms.

作者信息

Xu Rong, Du Yulan, Li Xiaomin, Mao Xinliang, Zheng Lin, Zhao Mouming

机构信息

School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China.

Perfect (China) Co., Ltd, Zhongshan, 528400, China.

出版信息

Food Funct. 2023 Nov 13;14(22):10240-10251. doi: 10.1039/d3fo02954a.

DOI:10.1039/d3fo02954a
PMID:37921641
Abstract

Our previous research showed that soluble (SC II) and insoluble (IC II) undenatured type II collagen had significant differences during gastrointestinal digestion , and SC II exposed more type II collagen with triple helix structure. However, the differences in their digestive characteristics, improvement on osteoarthritis (OA), and possible mechanisms have not been elucidated. The aim of this study was to explore these issues. After oral administration of SC II and IC II, the joint swelling of OA rats significantly reduced, and the weight bearing ratio of right hind limb significantly increased, especially in SC II group (raised to 48%). The Mankin and OARSI scores decreased by 35% and 48% in SC II group, respectively. SC II and IC II increased the mRNA expression of anti-inflammatory factors and the proportion of regulatory T cells (Treg). Importantly, type II collagen released by IC II during gastrointestinal digestion was far less than SC II, which explained the higher ability of SC II to induce immune tolerance in small intestine than IC II. Bioinformatics analysis showed that the differential genes between model and control were significantly enriched in PI3K/AKT, PPAR and AMPK signalling pathways, and 24 hub genes were analyzed. SC II significantly down-regulated the mRNA expression of Il6, Ccl7, NF-κB, AKT and up-regulated the mRNA expression of Scd1. These results showed that SC II was superior to IC II in improving OA by inducing immune tolerance and could regulate key biomarkers and signalling pathways in OA rats.

摘要

我们之前的研究表明,可溶性(SC II)和不溶性(IC II)未变性II型胶原蛋白在胃肠道消化过程中存在显著差异,且SC II暴露更多具有三螺旋结构的II型胶原蛋白。然而,它们在消化特性、对骨关节炎(OA)的改善作用以及可能的机制方面的差异尚未阐明。本研究的目的是探讨这些问题。口服SC II和IC II后,OA大鼠的关节肿胀明显减轻,右后肢负重比显著增加,尤其是在SC II组(提高到48%)。SC II组的Mankin和OARSI评分分别下降了35%和48%。SC II和IC II增加了抗炎因子的mRNA表达以及调节性T细胞(Treg)的比例。重要的是,IC II在胃肠道消化过程中释放的II型胶原蛋白远少于SC II,这解释了SC II在小肠中诱导免疫耐受的能力高于IC II。生物信息学分析表明,模型组和对照组之间的差异基因在PI3K/AKT、PPAR和AMPK信号通路中显著富集,并分析了24个枢纽基因。SC II显著下调了Il6、Ccl7、NF-κB、AKT的mRNA表达,并上调了Scd1的mRNA表达。这些结果表明,SC II在通过诱导免疫耐受改善OA方面优于IC II,并可调节OA大鼠的关键生物标志物和信号通路。

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