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泊洛沙姆188对氧化应激下肌肉细胞损伤机制的预防作用

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

作者信息

Wong Sing Wan, Yao Yifei, Hong Ye, Ma Zhiyao, Kok Stanton H L, Sun Shan, Cho Michael, Lee Kenneth K H, Mak Arthur F T

机构信息

Division of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.

School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.

出版信息

Ann Biomed Eng. 2017 Apr;45(4):1083-1092. doi: 10.1007/s10439-016-1733-0. Epub 2016 Sep 20.

Abstract

High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (HO). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by HO. These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

摘要

高氧化应激可发生在缺血再灌注和慢性炎症期间。据推测,这种氧化应激可能会导致诸如深部组织压疮等临床风险。骨骼肌可能会受到炎症诱导或再灌注诱导的氧化应激的挑战。据报道,氧化应激会降低骨骼肌细胞的抗压损伤阈值,导致肌动蛋白丝解聚,并降低膜封闭能力。因此,在长时间氧化暴露下,骨骼肌更容易受到机械负荷的损伤。在本研究中,我们研究了泊洛沙姆188(P188)对骨骼肌细胞抵抗外源性氧化应激(HO)的预防作用。研究发现,用1 mM P188预处理1小时后,骨骼肌细胞能够维持其抗压损伤阈值。就丝切蛋白、胸腺素β4和原肌球蛋白的表达而言,肌动蛋白聚合动力学基本保持稳定。激光穿孔实验表明,即使细胞受到HO的挑战,膜封闭能力仍得以保留。这些发现表明,P188预处理可帮助骨骼肌细胞在氧化环境中保持其正常的机械完整性,为P188对抗机械-氧化应激联合挑战增添了潜在的临床应用价值。这种作用可能有助于预防深部组织溃疡的发生。

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