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口服胶原蛋白肽对实验性大鼠骨关节炎模型的效果评估。

Evaluation of the effect of oral administration of collagen peptides on an experimental rat osteoarthritis model.

作者信息

Isaka Satoko, Someya Akimasa, Nakamura Shinji, Naito Kiyohito, Nozawa Masahiko, Inoue Naoki, Sugihara Fumihito, Nagaoka Isao, Kaneko Kazuo

机构信息

Department of Medicine for Motor Organ, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.

Department of Orthopaedic Surgery, Juntendo University, Nerima Hospital, Tokyo 117-8521, Japan.

出版信息

Exp Ther Med. 2017 Jun;13(6):2699-2706. doi: 10.3892/etm.2017.4310. Epub 2017 Apr 5.

Abstract

Collagen is an extracellular matrix protein present in the skin, tendon, cartilage and bone. Collagen peptides (CP) are produced by the hydrolysis of gelatin (heat-denatured collagen) by proteases and are utilized as a component of nutraceuticals. The current study investigated the effect of CP on the articular cartilage of OA by evaluating the serum levels of biomarkers (CTX-II for type II collagen degradation and CPII for type II collagen synthesis), histopathological changes (Mankin score, based on the toluidine blue staining of proteoglycans), and immunohistochemical staining of matrix metalloproteinase (MMP)-13 and type II collagen, using a rat experimental osteoarthritis (OA) model. Anterior cruciate ligament transection (ACLT) was performed on the right knee joint to surgically induce OA. Animals were divided into four groups: Control group (Control), sham-operated group (Sham), ACLT group without collagen peptide (ACLT group) and ACLT group with oral administration of CP (CP group). ACLT induced histological damages and significantly increased the Mankin score (P<0.05). However, CP administration markedly suppressed the Mankin score, although this difference was not significant. In addition, serum CTX-II levels were significantly decreased in CP group compared with those in the ACLT group (P<0.05). By contrast, serum CPII levels did not differ significantly among the four groups. Moreover, immunohistochemical staining of type II collagen and MMP-13 (an important type II collagen-degrading enzyme) indicated that the amount of type II collagen increased, whereas the number of MMP-13 positive chondrocytes decreased in the CP group compared with ACLT group. These observations suggest that CP has the potential to exert chondroprotective action on OA by inhibiting MMP-13 expression and type II collagen degeneration.

摘要

胶原蛋白是一种存在于皮肤、肌腱、软骨和骨骼中的细胞外基质蛋白。胶原肽(CP)是通过蛋白酶水解明胶(热变性胶原蛋白)产生的,并被用作营养保健品的一种成分。本研究通过评估生物标志物(用于II型胶原蛋白降解的CTX-II和用于II型胶原蛋白合成的CPII)的血清水平、组织病理学变化(基于蛋白聚糖甲苯胺蓝染色的曼金评分)以及基质金属蛋白酶(MMP)-13和II型胶原蛋白的免疫组化染色,利用大鼠实验性骨关节炎(OA)模型研究了CP对OA关节软骨的影响。对右膝关节进行前交叉韧带切断术(ACLT)以手术诱导OA。将动物分为四组:对照组(Control)、假手术组(Sham)、未给予胶原肽的ACLT组(ACLT组)和口服CP的ACLT组(CP组)。ACLT导致组织学损伤并显著增加曼金评分(P<0.05)。然而,给予CP显著抑制了曼金评分,尽管这种差异不显著。此外,与ACLT组相比,CP组血清CTX-II水平显著降低(P<0.05)。相比之下,四组之间血清CPII水平没有显著差异。此外,II型胶原蛋白和MMP-13(一种重要的II型胶原蛋白降解酶)的免疫组化染色表明,与ACLT组相比,CP组II型胶原蛋白的量增加,而MMP-13阳性软骨细胞的数量减少。这些观察结果表明,CP有可能通过抑制MMP-13表达和II型胶原蛋白变性对OA发挥软骨保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a27/5450616/f008988e52f4/etm-13-06-2699-g00.jpg

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