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厚朴减轻顺铂诱导的肌肉减少症小鼠模型中 M2 巨噬细胞介导的肌肉丢失。

Magnoliae Cortex Alleviates Muscle Wasting by Modulating M2 Macrophages in a Cisplatin-Induced Sarcopenia Mouse Model.

机构信息

Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, 26-6 Kyungheedae-ro, Dongdaemun-gu, Seoul 02453, Korea.

Department of Physiology, College of Korean Medicine, Kyung Hee University, 26-6 Kyungheedae-ro, Dongdaemun-gu, Seoul 02453, Korea.

出版信息

Int J Mol Sci. 2021 Mar 20;22(6):3188. doi: 10.3390/ijms22063188.

Abstract

Cachexia causes high mortality, low quality of life, and rapid weight loss in cancer patients. Sarcopenia, a condition characterized by the loss of muscle, is generally present in cachexia and is associated with inflammation. M2 macrophages, also known as an anti-inflammatory or alternatively activated macrophages, have been shown to play a role in muscle repair. Magnoliae Cortex (M.C) is a widely used medicinal herb in East Asia reported to have a broad range of anti-inflammatory activities; however, the effects of M.C on sarcopenia and on M2 macrophage polarization have to date not been studied. This study was designed to investigate whether the oral administration of M.C could decrease cisplatin-induced sarcopenia by modulating M2 macrophage polarization in mice. C57BL/6 mice were injected intraperitoneally with cisplatin (2.5 mg/kg) to mimic chemotherapy-induced sarcopenia. M.C extract (50, 100, and 200 mg/kg) was administered orally every 3 days (for a total of 12 times). M.C (100 and 200 mg/kg) significantly alleviated the cisplatin-induced loss of body mass, skeletal muscle weight, and grip strength. In addition, M.C increased the expression of M2 macrophage markers, such as MRC1, CD163, TGF-β, and Arg-1, and decreased the expression of M1-specific markers, including NOS2 and TNF-α, in skeletal muscle. Furthermore, the levels of like growth factor-1(IGF-1), as well as the number of M2a and M2c macrophages, significantly increased in skeletal muscle after M.C administration. M.C did not interfere with the anticancer effect of cisplatin in colon cancer. Our results demonstrated that M.C can alleviate cisplatin-induced sarcopenia by increasing the number of M2 macrophages. Therefore, our findings suggest that M.C could be used as an effective therapeutic agent to reverse or prevent cisplatin-induced sarcopenia.

摘要

恶病质导致癌症患者死亡率高、生活质量低和体重迅速下降。肌肉减少症是一种以肌肉丧失为特征的病症,通常存在于恶病质中,并与炎症有关。M2 巨噬细胞,也称为抗炎或替代激活的巨噬细胞,已被证明在肌肉修复中发挥作用。厚朴(M.C)是东亚广泛使用的药用植物,据报道具有广泛的抗炎活性;然而,M.C 对肌肉减少症和 M2 巨噬细胞极化的影响迄今为止尚未研究过。本研究旨在探讨 M.C 是否可以通过调节 M2 巨噬细胞极化来减少顺铂诱导的肌肉减少症。C57BL/6 小鼠腹腔注射顺铂(2.5mg/kg)模拟化疗诱导的肌肉减少症。M.C 提取物(50、100 和 200mg/kg)每天口服给药 3 次(共 12 次)。M.C(100 和 200mg/kg)显著减轻了顺铂引起的体重、骨骼肌重量和握力下降。此外,M.C 增加了 M2 巨噬细胞标志物的表达,如 MRC1、CD163、TGF-β和 Arg-1,并降低了骨骼肌中 M1 特异性标志物的表达,包括 NOS2 和 TNF-α。此外,M.C 给药后骨骼肌中 IGF-1 的水平以及 M2a 和 M2c 巨噬细胞的数量也显著增加。M.C 不干扰顺铂在结肠癌中的抗癌作用。我们的结果表明,M.C 通过增加 M2 巨噬细胞的数量来减轻顺铂诱导的肌肉减少症。因此,我们的研究结果表明,M.C 可用作一种有效的治疗剂来逆转或预防顺铂诱导的肌肉减少症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ae/8003985/1eb5ccd24ab5/ijms-22-03188-g001.jpg

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