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首页> 外文期刊>European Cells & Materials >A fine structural modification of glycosaminoglycans is correlated with the progression of muscle regeneration after ischaemia: towards a matrix-based therapy?
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A fine structural modification of glycosaminoglycans is correlated with the progression of muscle regeneration after ischaemia: towards a matrix-based therapy?

机译：糖胺聚糖的精细结构修饰与缺血后肌肉再生的进程有关：采用基于基质的疗法？

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Critical limb ischaemia often leads to amputation of the limb and potential mortality. Moreover, there are still significant problems with current therapeutic treatments, according to poor revascularisation of degenerated tissue probably due to modifications within the microenvironment. This study is focused on the changes of structure and bioactivity of glycosaminoglycans (GAGs), especially heparan sulphate (HS) and chondroitin sulphate (CS) in rat Extensor Digitorum Longus (EDL) muscle after ischaemia. Male Wistar rats were subjected to ischaemic-injury by ligation of the neurovascular trunk accompanying EDL-tendon. After 4, 8, 15, 21, 60 and 90 d, the rats were sacrificed and the muscles were collected and submitted to histological, biochemical and gene expression assays. We demonstrated that ischaemia induced modification of expression of enzymes involved in GAG biosynthesis which correlated with significant changes in HS and CS structural features such as size and sulphation pattern. These major structural changes are associated to modifications of GAG abilities to bind growth factors and to modulate cell activity. Moreover, a CS hallmark of injury is maintained as well after the regeneration process. Finally, we showed the relevance of the role of this glycanic matrix remodelling, since a GAG mimetic treatment accelerated muscle repair after ischaemia.
机译：严重肢体缺血常导致肢体截肢和潜在死亡率。此外，根据退化组织的不良血管重建，可能是由于微环境内的改变，目前的治疗方法仍然存在重大问题。这项研究的重点是缺血后大鼠伸指长肌（EDL）肌肉中糖胺聚糖（GAG），尤其是硫酸乙酰肝素（HS）和硫酸软骨素（CS）的结构和生物活性的变化。通过结扎EDL肌腱伴随的神经血管干对雄性Wistar大鼠进行缺血性损伤。在第4、8、15、21、60和90天后，处死大鼠并收集肌肉并进行组织学，生化和基因表达测定。我们证明了缺血导致与GAG生物合成有关的酶表达的修饰，这与HS和CS结构特征（例如大小和硫酸化模式）的显着变化相关。这些主要的结构变化与GAG结合生长因子和调节细胞活性的能力有关。此外，在再生过程之后也保持了CS损伤的特征。最后，我们证明了这种聚糖基质重塑作用的相关性，因为GAG模拟疗法可加速缺血后的肌肉修复。

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