Bifunctional Supramolecular Hydrogel Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy and Apoptosis
Bifunctional Supramolecular Hydrogel Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy and Apoptosis
复制标题
双功能超分子水凝胶通过抑制自噬和凋亡减轻心肌缺血/再灌注损伤
DOI：
10.1166/jbn.2018.2582
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发表时间：
2018-08-01
影响因子：
2.9
通讯作者：
Chen, Minsheng
中科院分区：
文献类型：
--
作者：
Deng, Yi;Chen, Guoqin;Chen, Minsheng
一般来说，一氧化氮（NO）是一种重要的多功能心脏保护可溶性气体分子。然而，当其含量过高或与O-2(-)（一种活性氧（ROS））结合形成ONOO-时，可能是有害的。后者将迅速分解为高活性氧化剂成分。缺血/再灌注 (I/R) 过程中会大量产生 ROS。因此，NO 供体与另一种抗氧化剂结合将是 I/R 治疗更有前途的策略。在这项研究中，我们报道了一种新型自组装超分子水凝胶，能够同时持续释放NO和姜黄素（Cur），我们发现凝胶中的Cur和NO的联合治疗可以有效减少I/R损伤。其潜在机制表明，水凝胶可以降低 ROS 水平，从而抑制 ROS 相关的 p38 MAPK/NF-kappa B 信号通路的表达。此外，水凝胶还显着抑制了 I/R 治疗期间过度刺激的自噬和细胞凋亡，这是介导严重缺血后心肌细胞死亡的原因。结果表明，我们的超分子水凝胶是一种有前途的治疗心肌缺血再灌注损伤的生物材料。
Generally, nitric oxide (NO) is an important multi-functional cardioprotective soluble gas molecule. However, it may be detrimental when in excessive levels or combined with O-2(-) a kind of reactive oxygen species (ROS)-to form ONOO-. The latter will rapidly decompose to highly reactive oxidant components. ROS will be abundantly produced during the ischemia/reperfusion (I/R) procedure. Therefore, an NO donor coupled with another antioxidant would be a more promising strategy for I/R treatment. In this study, we report on a novel self-assembly supramolecular hydrogel capable of constantly releasing both NO and curcumin (Cur) simultaneously, and we found that the combinational treatment of Cur and NO from the gel could efficiently reduce I/R injuries. The underlining mechanism revealed that the hydrogel could reduce the ROS level and thus inhibit the expression of the ROS-associated p38 MAPK/NF-kappa B signaling pathway. Moreover, the hydrogel also significantly suppressed over-stimulated autophagy and apoptosis during I/R treatment which was responsible for mediating severe post-ischemia myocardial cell death. The results indicated that our supramolecular hydrogel was a promising biomaterial for the treatment of myocardial I/R injuries.