Effect of hypoxia-inducible factor 1 alpha inhibitor on immobilization-induced muscle fibrosis related to muscle contracture.

Yasuhiro Kajiwara, Yuichiro Honda, Ayumi Takahashi, Seima Okita, Jumpei Miyake, Yudai Ishiki, Chiaki Seguchi, Junya Sakamoto, Minoru Okita
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Abstract

[Purpose] To test the effect of the hypoxia-inducible factor 1-alpha (HIF-1α) inhibitor, YC-1, on the upregulation of HIF-1α that leads to immobilization-induced muscle fibrosis underlying muscle contracture. [Materials and Methods] Rats were divided into control, immobilization (immobilization only), and YC-1 (immobilization and YC-1 injection) groups. The soleus muscles were the specimens. [Results] The HIF-1α protein expression in the control, immobilization, and YC-1 groups was 0.26 ± 0.11, 0.94 ± 0.28, and 0.66 ± 0.15, respectively. The expression of HIF-1α protein in the immobilization and YC-1 groups was significantly higher than in the control group and it was lower in the YC-1 group than in the immobilization group. There were strong positive correlations between HIF-1α protein expression and transforming growth factor (TGF)-β1 mRNA expression, TGF-β1 and α-smooth muscle actin (SMA) mRNA expressions, and between α-SMA mRNA expression and hydroxyproline content. A strong negative correlation was found between hydroxyproline content and range of motion on dorsiflexion at four-weeks. [Conclusion] Inhibition of HIF-1α may contribute to suppressing the overexpression of fibrosis-related molecules triggered by upregulation of HIF-1α, which may mitigate immobilization-induced muscle fibrosis related to muscle contracture.

缺氧诱导因子1 α抑制剂对与肌肉挛缩相关的固定化诱导肌肉纤维化的影响。
[目的]探讨缺氧诱导因子1- α (HIF-1α)抑制剂YC-1在HIF-1α上调中导致肌肉挛缩所致肌肉纤维化的作用。【材料与方法】将大鼠分为对照组、固定化组(仅固定化)和YC-1组(固定化并注射YC-1)。以比目鱼肌为标本。[结果]对照组、固定化组和YC-1组HIF-1α蛋白表达量分别为0.26±0.11、0.94±0.28和0.66±0.15。HIF-1α蛋白在固定组和YC-1组的表达量均显著高于对照组,YC-1组的表达量低于固定组。HIF-1α蛋白表达与转化生长因子(TGF)-β1 mRNA表达、TGF-β1与α-平滑肌肌动蛋白(SMA) mRNA表达、α-SMA mRNA表达与羟脯氨酸含量呈正相关。羟基脯氨酸含量与4周时背屈活动度呈显著负相关。[结论]抑制HIF-1α可能有助于抑制HIF-1α上调引发的纤维化相关分子的过表达,从而减轻与肌肉挛缩相关的固定化诱导的肌肉纤维化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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137
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4-8 weeks
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