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在大鼠脂肪性肌肉变性模型中,注射脂肪来源的间充质干/基质细胞可抑制肌肉萎缩标志物和脂肪生成标志物。

Injection of Adipose-Derived Mesenchymal Stem/Stromal Cells Suppresses Muscle Atrophy Markers and Adipogenic Markers in a Rat Fatty Muscle Degeneration Model.

作者信息

Koung Ngeun Sai, Shimizu Miki, Kaneda Masahiro

机构信息

Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu 183-8509, Tokyo, Japan.

Department of Veterinary Anatomy, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu 183-8509, Tokyo, Japan.

出版信息

Curr Issues Mol Biol. 2024 Jul 24;46(8):7877-7894. doi: 10.3390/cimb46080467.

Abstract

Fatty muscle degeneration and muscle atrophy have not been successfully treated due to their irreversible pathology. This study evaluated the efficacy of rat adipose-derived mesenchymal stem/stromal cells (ADP MSCs) in treating fatty muscle degeneration (FD). A total of 36 rats were divided into three groups: the control (C) group ( = 12); FD model group, generated by sciatic nerve crushing ( = 12); and the group receiving ADP MSC treatment for FD (FD+MSCs) ( = 12). In Group FD+MSCs, ADP MSCs were injected locally into the gastrocnemius muscle one week after the FD model was created (Day 8). On Day 22 ( = 18) and Day 43 ( = 18), muscle morphology, histopathology, and molecular analyses (inflammation, muscle atrophy, adipocytes, and muscle differentiation markers) were performed. In Group FD+MSCs, the formation of immature myofibers was observed on Day 22, and mitigation of fatty degeneration and muscle atrophy progression was evident on Day 43. Gene expression of muscle atrophy markers (, , and ) and adipogenic markers (, , , and ) was lower in Group FD+MSCs than Group FD on Day 43. ADP MSCs induce anti-inflammatory effects, inhibit fat accumulation, and promote muscle regeneration, highlighting their potential as promising therapy for FD and atrophy.

摘要

由于脂肪性肌肉变性和肌肉萎缩具有不可逆的病理特征,其治疗尚未取得成功。本研究评估了大鼠脂肪来源的间充质干/基质细胞(ADP间充质干细胞)治疗脂肪性肌肉变性(FD)的疗效。总共36只大鼠被分为三组:对照组(C组)(n = 12);通过坐骨神经挤压建立的FD模型组(n = 12);以及接受ADP间充质干细胞治疗FD的组(FD + MSCs组)(n = 12)。在FD + MSCs组中,在FD模型建立后一周(第8天)将ADP间充质干细胞局部注射到腓肠肌中。在第22天(n = 18)和第43天(n = 18)进行肌肉形态学、组织病理学和分子分析(炎症、肌肉萎缩、脂肪细胞和肌肉分化标志物)。在FD + MSCs组中,在第22天观察到未成熟肌纤维的形成,并且在第43天脂肪变性和肌肉萎缩进展的减轻明显。在第43天,FD + MSCs组中肌肉萎缩标志物(Atrogin-1、MuRF1和MyoD)和成脂标志物(PPARγ、aP2、LPL和FABP4)的基因表达低于FD组。ADP间充质干细胞具有抗炎作用,抑制脂肪积累,并促进肌肉再生,突出了它们作为FD和萎缩的有前景治疗方法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6453/11352917/8d69db6525f4/cimb-46-00467-g001.jpg

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