Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway.
Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway.
复制标题
DOI：
10.1038/srep44579
复制
发表时间：
2017-03-22
影响因子：
4.6
通讯作者：
Han JY
中科院分区：
文献类型：
--
作者：
Cui YC;Pan CS;Yan L;Li L;Hu BH;Chang X;Liu YY;Fan JY;Sun K;-Li Q;Han JY
心肌缺血再灌注损伤一直是临床医生面临的挑战。据报道，人参皂甙Rb 1（Rb 1）具有减轻I/R损伤的能力，但其对心脏I/R期间能量代谢的影响及其潜在机制尚不清楚。本研究观察了Rb 1对大鼠心肌缺血再灌注损伤时心肌血流量、心肌梗死面积、心功能、微静脉红细胞速度、心肌结构和细胞凋亡、能量代谢的影响以及RhoA信号通路的变化。此外，RhoA与Rb 1的结合亲和力使用表面等离子体共振（SPR）检测。结果表明，Rb 1 5 mg/kg/h对I/R引起的心肌结构损伤、心肌血流量减少、心功能和微循环障碍、心肌细胞凋亡、心肌梗死和心肌cTnI释放均有保护作用。Rb 1还能抑制RhoA信号通路的激活，恢复心肌I/R时ATP的生成。SPR实验表明，Rb 1能够与RhoA结合，并呈剂量依赖性。这些结果表明Rb 1可能通过调节RhoA信号通路来预防I/R诱导的心脏损伤，并可能作为改善经皮冠状动脉介入治疗结果的潜在方案。
Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury. In addition, the binding affinity of RhoA to Rb1 was detected using surface plasmon resonance (SPR). Results showed that Rb1 treatment at 5 mg/kg/h protected all the cardiac injuries induced by I/R, including damaged myocardial structure, decrease in myocardial blood flow, impaired heart function and microcirculation, cardiomyocyte apoptosis, myocardial infarction and release of myocardial cTnI. Rb1 also inhibited the activation of RhoA signaling pathway and restored the production of ATP during cardiac I/R. Moreover, SPR assay showed that Rb1 was able to bind to RhoA in a dose-dependent manner. These results indicate that Rb1 may prevent I/R-induced cardiac injury by regulation of RhoA signaling pathway, and may serve as a potential regime to improve percutaneous coronary intervention outcome.