Redox Status and Muscle Pathology in Rheumatoid Arthritis: Insights from Various Rat Hindlimb Muscles

Redox Status and Muscle Pathology in Rheumatoid Arthritis: Insights from Various Rat Hindlimb Muscles
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DOI:
10.1155/2019/2484678
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发表时间:
2019-01-01
影响因子:
--
通讯作者:
Smith, C.
Smith, C.
中科院分区:
生物学2区
文献类型:
--
作者:
Oyenihi, A. B.;Ollewagen, T.;Smith, C.

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由于萎缩,肌肉无力是类风湿性关节炎(RA)的常见现象。大多数人体研究都是在股外侧肌(一种混合纤维类型的肌肉)上进行的,但在啮齿动物或人类模型中,几乎没有多块肌肉之间的比较数据。因此,本研究评估了雌性Sprague-Dawley大鼠胶原诱导类风湿性关节炎模型中各种肌肉的肌肉超微结构和选定的氧化还原指标。与非RA对照组相比,RA动物中只有腓肠肌、趾长伸肌(EDL)和比目鱼肌这三块肌肉的肌肉质量较低(分别损失38%、27%和25%,均至少P < 0.01),而股外侧肌的肌肉质量增加了35%(P < 0.01)。然而,所有四块肌肉都表现出指示类风湿性恶病质的恶化迹象。腓肠肌、趾长伸肌和比目鱼肌的横截面积同样减少(分别为60%、58%和64%;均P < 0.001),但股外侧肌(减少22%,P < 0.05)受影响较小,而肌肉中的胶原沉积显著增加。这种病理学与除股外侧肌外的所有肌肉中活性氧(ROS)的组织水平显著增加相关,而只有腓肠肌的脂质过氧化(TBARS)和抗氧化活性(FRAP)水平显著增加。目前的数据说明了不同的后肢骨骼肌慢性炎症的挑战,无论是在氧化还原变化和恶病质的抵抗力的差异反应。
Due to atrophy, muscle weakness is a common occurrence in rheumatoid arthritis (RA). The majority of human studies are conducted on the vastus lateralis muscle-a muscle with mixed fiber type-but little comparative data between multiple muscles in either rodent or human models are available. The current study therefore assessed both muscle ultrastructure and selected redox indicators across various muscles in a model of collagen-induced rheumatoid arthritis in female Sprague-Dawley rats. Only three muscles, the gastrocnemius, extensor digitorum longus (EDL), and soleus, had lower muscle mass (38%, 27%, and 25% loss of muscle mass, respectively, all at least P < 0.01), while the vastus lateralis muscle mass was increased by 35% (P < 0.01) in RA animals when compared to non-RA controls. However, all four muscles exhibited signs of deterioration indicative of rheumatoid cachexia. Cross-sectional area was similarly reduced in gastrocnemius, EDL, and soleus (60%, 58%, and 64%, respectively; all P < 0.001), but vastus lateralis (22% smaller, P < 0.05) was less affected, while collagen deposition was significantly increased in muscles. This pathology was associated with significant increases in tissue levels of reactive oxygen species (ROS) in all muscles except the vastus lateralis, while only the gastrocnemius had significantly increased levels of lipid peroxidation (TBARS) and antioxidant activity (FRAP). Current data illustrates the differential responses of different skeletal muscles of the hindlimb to a chronic inflammatory challenge both in terms of redox changes and resistance to cachexia.