Role of high-mobility group B1 in myocardial injury induced by coronary microembolization in rats
Role of high-mobility group B1 in myocardial injury induced by coronary microembolization in rats
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高活动度B1组在冠状动脉微栓塞致大鼠心肌损伤中的作用
DOI：
10.1002/jcb.27709
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Zeng, Xiang-Tao
中科院分区：
文献类型：
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作者：
Chen, Quan-Fang;Wang, Wei;Zeng, Xiang-Tao
目的探讨高迁移率组B1 （HMGB1）对大鼠冠状动脉微栓塞（CME）所致心肌炎症、心肌凋亡及心功能损伤的影响。方法将40只Sprague-Dawley大鼠分为假手术组（sham组）、微栓塞组（CME组）、CME + HMGB1 siRNA组（HMGB1 siRNA）和CME +混乱siRNA（对照siRNA）组（每组10只）。CME模型组采用夹持升主动脉后在左心室尖部注射微栓塞球的方法构建。假手术组注射等量生理盐水。HMGB1 siRNA组在CME建模前72小时通过尾静脉注射HMGB1 siRNA转染复合物。对照组siRNA在CME建模前72小时通过尾静脉注射等量的搅乱siRNA混合物。术后12 h检测心功能、血清心肌肌钙蛋白I水平及细胞凋亡指数。检测HMGB1、核因子κ B (nf - κ B) p65、葡萄糖调节蛋白78 （GRP78）、C/EBP同源蛋白（CHOP）、cleaved caspase-12、cleaved caspase-3、肿瘤坏死因子α (tnf - α)、白细胞介素1 β (IL-1 β)水平。结果CME诱导心肌功能障碍，血清肌钙蛋白I水平升高，细胞凋亡指数升高。此外，CME增加了HMGB1、NF-kappa B p65、GRP78、CHOP、cleaved caspase-12、cleaved caspase-3、tnf - α和IL-1 β的表达。HMGB1 siRNA逆转了这些影响，而打乱的siRNA则没有影响。结论抑制HMGB1表达可减轻cme所致心肌损伤，改善心功能。因此，它可能成为预防和治疗cme所致心肌损伤的新靶点。
Objective This study aimed to explore the effects of high-mobility group B1 (HMGB1) on coronary microembolization (CME)-induced myocardial inflammation, myocardial apoptosis, and cardiac function injury in rats. Methods Forty Sprague-Dawley rats were divided into sham operation group (sham group), microembolization group (CME group), CME + HMGB1 siRNA (HMGB1 siRNA) group, and CME + scrambled siRNA (control siRNA) group (10 rats in each group). The CME model group was constructed by injecting microembolism spheres into the apex of the left ventricle after clamping the ascending aorta. The sham group was constructed by injecting the same amount of saline. The HMGB1 siRNA group was injected with HMGB1 siRNA transfection complex via the tail vein 72 hours before CME modeling. The control siRNA group was injected with the same amount of scrambled siRNA mixture through the tail vein 72 hours before CME modeling. The cardiac function, serum cardiac troponin I level, and apoptotic index were examined 12 hours after the surgery. The levels of HMGB1, nuclear factor-kappa B (NF-kappa B) p65, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, cleaved caspase-3, tumor necrosis factor-alpha (TNF-alpha), and interleukin 1 beta (IL-1 beta) were detected. Results Myocardial dysfunction, enhanced serum cardiac troponin I level, and apoptotic index were induced following CME. Moreover, CME increased the expression of HMGB1, NF-kappa B p65, GRP78, CHOP, cleaved caspase-12, cleaved caspase-3, TNF-alpha, and IL-1 beta. HMGB1 siRNA reversed these effects, whereas scrambled siRNA had no effect. Conclusions Inhibition of HMGB1 expression reduced CME-induced myocardial injury and improved cardiac function. Hence, it may serve as a new target for preventing and treating the CME-induced myocardial injury.