Dexmedetomidine preconditioning mitigates myocardial ischemia/reperfusion injury via inhibition of mast cell degranulation.
Dexmedetomidine preconditioning mitigates myocardial ischemia/reperfusion injury via inhibition of mast cell degranulation.
复制标题
右美托咪定预处理通过抑制肥大细胞脱颗粒减轻心肌缺血/再灌注损伤。
DOI：
10.1016/j.biopha.2021.111853
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发表时间：
2021-05
影响因子：
7.5
通讯作者：
Qian Jinqiao
中科院分区：
文献类型：
--
作者：
Xiong Wei;Zhou Rui;Qu Yan;Yang Yuqiao;Wang Zhuoran;Song Ning;Liang Rongbi;Qian Jinqiao
心肌肥大细胞脱颗粒与心肌缺血/再灌注损伤的发生、发展密切相关。右美托咪定对I/R损伤具有心脏保护作用。本研究旨在探讨右美托咪定预处理诱导的心肌保护作用是否与抑制心肌肥大细胞脱颗粒有关。体内外实验结果显示，I/R损伤组的血流动力学紊乱、心律失常、心肌梗死面积、病理组织学评分和肥大细胞脱颗粒均较非I/R组明显增加，肥大细胞促分泌剂化合物48/80加重了这些损伤，而右美托咪定预处理可改善这些损伤。类似地，化合物48/80增加I/R损伤诱导的心脏组织中心肌肌钙蛋白I（cTnI）和类胰蛋白酶的水平、心肌细胞凋亡以及高迁移率族蛋白盒1（HMGB 1）、toll样受体4（TLR 4）和核因子-κ B p65（NF-κB p65）的表达，但其可通过右旋美托咪啶预处理而部分降低。化合物48/80抑制H9 C2（2−1）和RBL-2 H3的增殖，加剧H9 C2（2−1）的凋亡，并升高cTnI和类胰蛋白酶的水平，而这两者都被右美托咪定预处理消除。提示右美托咪定预处理可减轻I/R损伤引起的肥大细胞脱颗粒和心肌细胞凋亡，抑制炎症相关因子HMGB 1、TLR 4和NF-κB p65的活化。
The degranulation of cardiac mast cells is associated with occurrence and development of myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has a cardioprotective effect from I/R injury. The purpose of this study was to investigate whether dexmedetomidine preconditioning induced cardioprotection is related to suppression of degranulation of cardiac mast cell. Bothin vivoandin vitroexperimental results revealed that hemodynamic disorder, arrhythmia, infarct size, histopathological score, and mast cell degranulation were dramatically increased in I/R injury groups compared with non-I/R groups, and mastocyte secretagogue compound 48/80 aggravated these damages, but it can be improved by dexmedetomidine preconditioning. Similarly, compound 48/80 increased levels of cardiac troponin I (cTnI) and tryptase, cardiomyocytes apoptosis, and expression of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and nuclear factor-kappa B p65(NF-κB p65) in cardiac tissues induced by I/R injury, but it can be partially decreased by dexmedetomidine pretreatment. Compound 48/80 inhibited proliferation of H9C2(2−1) and RBL-2H3, exacerbated apoptosis of H9C2(2−1), and elevated levels of cTnI and tryptase, while both of which were abolished by dexmedetomidine pretreatment. Our data suggest that dexmedetomidine preconditioning alleviates the degranulation of mast cells and the apoptosis of cardiomyocytes caused by I/R injury, and inhibits the activation of inflammatory related factors HMGB1, TLR4, and NF-κB p65.