Purpose

Anti-inflammatory therapy is important for reducing myocardial injury after acute myocardial infarction (MI). New anti-inflammatory drugs and their mechanism are necessary to be explored to improve clinical efficacy. We aimed to improve the efficacy of colchicine on attenuating MI injury by nano-drug delivery systems and to investigate the mechanism of anti-inflammatory.

Methods

A colchicine-containing delivery system based on calcium carbonate nanoparticles (ColCaNPs) was synthesized. The protection against MI by ColCaNPs was evaluated using an in vivo rat model established by ligating the left anterior descending coronary artery. Macrophage polarization and the levels of inflammatory cytokines were determined using immunohistochemistry, Western blot, and ELISA analysis.

Results

ColCaNP treatment showed about a 45% reduction in myocardial infarct size and attenuating myocardial fibrosis compared with groups without drug intervention after MI. Furthermore, ColCaNPs significantly decreased the levels of CRP, TNF-α, and IL-1β in serum and the expression of proinflammatory cytokine in myocardial tissues after MI (p < 0.05). We also found that ColCaNPs notably restrained pyroptosis and inhibited inflammatory response by modulating on M1/M2 macrophage polarization and suppressing TLR4/NFκB/NLRP3 signal pathway.

Conclusion

Colchicine-containing nanoparticles can protect against MI injury in a clinically relevant rat model by reducing inflammation. In addition, calcium carbonate nanoparticles can increase the cardioprotective effects of colchicine.

中文翻译：

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含秋水仙碱的纳米颗粒通过抑制炎症减轻急性心肌梗死损伤

目的

抗炎治疗对于减少急性心肌梗死（MI）后的心肌损伤很重要。有必要探索新的抗炎药物及其作用机制以提高临床疗效。我们旨在通过纳米药物递送系统提高秋水仙碱减轻 MI 损伤的功效，并研究其抗炎机制。

方法

合成了基于碳酸钙纳米颗粒 (ColCaNPs) 的含秋水仙碱的递送系统。使用通过结扎冠状动脉左前降支建立的体内大鼠模型评估 ColCaNPs 对 MI 的保护作用。使用免疫组织化学、蛋白质印迹和 ELISA 分析确定巨噬细胞极化和炎性细胞因子水平。

结果

与 MI 后未进行药物干预的组相比，ColCaNP 治疗显示心肌梗塞面积减少约 45%，心肌纤维化减弱。此外，ColCaNPs 显着降低了 MI 后血清中 CRP、TNF-α 和 IL-1β 的水平以及心肌组织中促炎细胞因子的表达（p  < 0.05）。我们还发现 ColCaNPs 通过调节 M1/M2 巨噬细胞极化和抑制 TLR4/NFκB/NLRP3 信号通路显着抑制细胞焦亡和炎症反应。

结论

含有秋水仙碱的纳米颗粒可以通过减少炎症来防止临床相关大鼠模型中的 MI 损伤。此外，碳酸钙纳米颗粒可以增加秋水仙碱的心脏保护作用。