Characterization of early myocardial inflammation in ischemia-reperfusion injury.
Characterization of early myocardial inflammation in ischemia-reperfusion injury.
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DOI：
10.3389/fimmu.2022.1081719
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
心肌缺血再灌注（IR）可能引起心肌损伤，抢救这种损伤在临床实践中仍然是一个很大的挑战。本研究全面表征IR后心肌损伤的生理病理变化，探讨其在早期再灌注阶段的潜在机制，重点关注早期心肌炎症。采用C57BL/6小鼠左前降支短暂结扎法建立IR模型。T2W信号在不同IR阶段均呈升高趋势。它与炎症细胞因子和细胞呈正相关。7.0 T MRI T2W显像意外发现信号增强，但组织病理学和流式细胞术在IR后3小时内未发现任何炎症细胞浸润。WGA染色观察心肌细胞肿胀，超微结构分析观察血管通透性增加。3 h IR组心肌细胞严重受损，肌丝和线粒体解体。与sham组相比，3 h IR组VEGF和磷酸化Src蛋白均有显著表达，TUNEL染色显示阳性细胞较少。Cleaved caspase-3 apoptin的表达水平与sham组相似。常驻巨噬细胞明显变为M1表型。T2W信号仍然升高，我们观察到胶原沉积发生在1 ~ 7天。再灌注损伤后第1周的炎症反应在3 h后逐渐增强，但在此之前主要表现为水肿。本研究提示，由于炎症细胞浸润缺失和凋亡导致的再灌注性心肌损伤，前3小时可能是早期抢救过程的关键。
Myocardial injury may be caused by myocardial ischemia-reperfusion (IR), and salvaging such an injury is still a great challenge in clinical practice. This study comprehensively characterized the physiopathologic changes of myocardial injury after IR to explore the underlying mechanism in the early reperfusion phase with particular emphasis on early myocardial inflammation. The experimental IR model was obtained by the left anterior descending artery’s transient ligation of C57BL/6 mice. T2W signals of all mice showed increased signal at different IR stages. It was positively correlated with inflammatory cytokines and cells. T2W imaging by 7.0 T MRI surprisingly detected signal enhancement, but histopathology and flow cytometry did not reveal any inflammatory cells infiltration within 3 h after IR. Cardiomyocyte swelling and increased vascular permeability were observed by WGA staining and ultrastructural analysis, respectively. The 3 h IR group showed that the cardiomyocytes were severely affected with disintegrating myofilaments and mitochondria. Both VEGF and phosphorylated Src protein were markedly expressed in the 3 h IR group in comparison with the sham group, and TUNEL staining displayed little positive cells. Cleaved caspase-3 apoptin also has similar expression levels with that of the sham group. Resident macrophages had notably become M1 phenotype. The T2W signal was still elevated, and we observed that collagen deposition occurred from 1 to 7 days. The inflammation response during the first week after reperfusion injury gradually increase 3 h later, but the main manifestation before that was edema. This study indicated that the first 3 h may be crucial to the early rescue process for reperfusion-induced myocardial injury due to inflammatory cell infiltration absence and apoptosis.
影响因子：
4.6
作者：
de Haan JJ;Bosch L;Borgman A;Bastemeijer M;Brans MAD;van de Weg SM;de Kleijn DPV;Sluijter JPG;El Azzouzi H;de Jager SCA
通讯作者：
de Jager SCA
输注后期预处理血浆的心脏保护作用可能是通过激活大鼠再灌注损伤挽救激酶途径而非幸存者激活因子增强途径诱导的
影响因子：
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作者：
Zhao Y;Zheng ZN;Pi YN;Liang X;Jin SQ
通讯作者：
Jin SQ