Sustained-Release Hydrogel-Based Rhynchophylline Delivery System Improved Injured Tendon Repair
Sustained-Release Hydrogel-Based Rhynchophylline Delivery System Improved Injured Tendon Repair
复制标题
基于水凝胶的缓释钩藤碱输送系统改善了受伤肌腱的修复
DOI：
10.1016/j.colsurfb.2021.111876
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发表时间：
2021-06-01
影响因子：
5.8
通讯作者：
Zhou，You Lang
中科院分区：
文献类型：
--
作者：
Yang，Qian Qian;Zhang，Luzhong;Zhou，You Lang
在损伤的屈肌腱愈合过程中，肌腱组织容易与周围组织形成极致密的粘连，严重影响手功能的恢复。钩藤在临床上应用广泛，其主要成分钩藤碱（Rhynchophylline，Rhy）具有良好的治疗效果，能有效抑制腹腔粘连的形成。然而，Rhy对肌腱愈合和粘连形成的治疗作用仍不清楚。由于Rhy的半衰期短，因此构建了用于Rhy递送的透明质酸（HA）缓释系统，该系统还可以避免药物在运输过程中的不希望的损失。在损伤肌腱周围应用Rhy输送系统后，评价肌腱的粘连形成、滑动功能和愈合强度。结果表明，修复肌腱的滑动位移和愈合强度均明显增加，粘连得到抑制。在体实验中，Rhy可促进成纤维细胞Col Ⅰ/Col Ⅲ的表达，促进成纤维细胞有序组织化，形成肌腱组织。体外研究表明Rhy能促进TGF-β1刺激的肌腱细胞恢复正常的细胞功能，包括细胞增殖和凋亡水平。通过高通量测序，我们发现Rhy参与了细胞外基质（ECM）信号通路的调控。结论：Rhy通过抑制Smad 2的磷酸化，促进肌腱愈合，防止粘连形成。因此，Rhy的缓释系统有望成为肌腱损伤治疗的一种新方法。
During the injured flexor tendon healing process, tendon tissue is easy to form extremely dense adhesion with the surrounding tissue, which causes the serious influence of hand function recovery. Uncaria is widely used in clinic and its main composition, Rhynchophylline (Rhy), has been reported on its good therapeutic effect, which could effectively inhibit the intra-abdominal adhesion formation. However, the therapeutic effect of Rhy on tendon healing and adhesion formation is still unclear. Due to the short half-life of Rhy, hyaluronic acid (HA) sustained-release system for Rhy delivery was constructed and it could also avoid drug from the undesired loss during the transit. After Rhy delivery system was applied around the injured tendons, adhesion formation, gliding function and healing strength of tendons were evaluated. Our results showed that the gliding excursion and healing strength of repaired tendons were both significantly increased, as well as the adhesion was inhibited. Fromin vivoexperiments, Rhy could be able to increase the expression of Col Ⅰ/Col Ⅲ and helped fibroblasts to ordered organization for tendon tissues. But for adhesion tissues, Rhy promoted the apoptosis and accelerated the degradation of extracellular matrix.In vitrostudy showed Rhy could help tenocytes stimulated with TGF-β1 to recover to normal cell functions involving cell proliferation and apoptosis level. Through high-throughput sequencing, we found that Rhy was involved in the regulation of Extracellular Matrix (ECM) signaling pathway. We draw a conclusion that Rhy enhanced the tendon healing and prevented adhesion formation through inhibiting the phosphorylation of Smad2. In a word, this sustained release system of Rhy may be a promising strategy for the treatment of injured tendons.