Department of Cardiology, Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University, No. 151 East Section of South Second Ring RoadBeilin District, Xi'an, 710054, Shaanxi, China.
Medical College of Yan'an University, No. 38 Guanghua RoadBaota District, Yan'an, 716000, Shaanxi, China.
Appl Biochem Biotechnol. 2022 Mar;194(3):1149-1165. doi: 10.1007/s12010-021-03680-z. Epub 2021 Oct 1.
Preconditioning with Peoniflorin, a component of traditional Chinese prescriptions, was proposed to be a potential strategy for cardioprotection against ischemia/reperfusion (I/R) injury. However, the cardioprotective effect of Peoniflorin preconditioning has not been thoroughly confirmed, and the underlying mechanism remains unclear. Here, we examined the cardioprotective effect and its mechanism of Peoniflorin preconditioning against myocardial I/R injury. Rats were subjected to 30 min of transient ischemia followed by 2 h of reperfusion with or without Peoniflorin (100 mg/kg) prior to reperfusion. Peoniflorin preconditioning significantly limited myocardial infarct size and reperfusion arrhythmias, as well as obviously attenuated the histomorphological and micromorphological damages induced by I/R injury. The reduced myocardial injury was also associated with the anti-apoptotic effect of Peoniflorin, as evidence by decreased TUNEL-positive cells, upregulation of BCL-2 expression, and downregulation of Bax and caspase-3 expression. In an effort to evaluate the mechanism responsible for the observed cardioprotective and anti-apoptotic effect, Western blot of phosphorylated protein was performed after 20 min of reperfusion. Results showed that Peoniflorin preconditioning activated both the Akt and ERK1/2 arm of the reperfusion injury salvage kinase (RISK) pathway. To further confirm this mechanism, the PI3K signaling inhibitor LY294002 and ERK1/2 signaling inhibitor PD98059 were administered in vivo. The cardioprotective and anti-apoptotic effects of Peoniflorin preconditioning were diminished but not abolished by pretreatment with LY294002 or PD98059. Taken together, these results indicate that Peoniflorin preconditioning protects the myocardial against I/R injury and inhibits myocardial apoptosis via the activation of the RISK pathway, highlighting the potential therapeutic effects of Peoniflorin on reducing myocardial I/R injury.
预先给予芍药苷（一种传统中药方剂的成分）预处理被提出是一种潜在的针对缺血/再灌注（I/R）损伤的心脏保护策略。然而，芍药苷预处理的心脏保护作用尚未得到充分证实，其潜在机制仍不清楚。在这里，我们研究了芍药苷预处理对心肌 I/R 损伤的心脏保护作用及其机制。在再灌注前，大鼠经历 30 分钟短暂缺血，随后再灌注 2 小时，同时给予或不给予芍药苷（100mg/kg）。芍药苷预处理显著限制了心肌梗死面积和再灌注心律失常，明显减轻了 I/R 损伤引起的组织形态和微形态损伤。减少的心肌损伤也与芍药苷的抗凋亡作用有关，表现为 TUNEL 阳性细胞减少、BCL-2 表达上调和 Bax 和 caspase-3 表达下调。为了评估观察到的心脏保护和抗凋亡作用的机制，在再灌注 20 分钟后进行磷酸化蛋白的 Western blot。结果表明，芍药苷预处理激活了再灌注损伤 salvage 激酶（RISK）通路的 Akt 和 ERK1/2 分支。为了进一步证实这一机制，体内给予 PI3K 信号抑制剂 LY294002 和 ERK1/2 信号抑制剂 PD98059。芍药苷预处理的心脏保护和抗凋亡作用被 LY294002 或 PD98059 预处理部分减弱，但并未完全消除。综上所述，这些结果表明，芍药苷预处理通过激活 RISK 通路保护心肌免受 I/R 损伤并抑制心肌细胞凋亡，突出了芍药苷在减少心肌 I/R 损伤方面的潜在治疗作用。
