Cardioprotective effects of Yiqi Yangyin Huoxue Injection against ischemia-reperfusion injury in isolated hearts of rats
LI Yu-hong;LI Yan-yan;FAN Guan-wei;ZHOU Kun;DUAN Zhen-zhen;YU Jia-hui;GAO Xiu-mei;Tianjin State Key Laboratory of Modern Chinese Medicine,Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine;
Objective To clarify the cardioprotective effects of Yiqi Yangyin Huoxue(YYH) Injection exert against ischemia-reperfusion(I/R) injury, and the mechanisms involving activation of specific survival signals reperfusion injury salvage kinase(PI3K-Akt pathway and ERK1/2 pathway), hence inhibiting mitochondrial permeability transition pore opening(m PTP). Methods A Langendorff model of myocardial ischemia-reperfusion injury was employed. The rats were randomly divided into seven groups: control group, I/R group, YYH 2.5, 5, and 10 μL/m L groups, LY294002 + YYH 10 μL/m L group, and LY294002 group. The cardiac parameters of left ventricular developed pressure(LVDP), maximal rise/fall of left ventricular pressure(± dp/dtmax), and rate-pressure product(RPP) were monitored. Creatine kinase(CK) and lactate dehydrogenase(LDH) released from effluents were measured. Infarct size was estimated by TTC staining. Transmission electron microscopy(TEM) was performed to assess morphological difference between cardiac mitochondrial isolated I/R rats and YYH pretreated rats. Western blotting was used to determine some protein expression. MPTP opening in mitochondria isolated from Langendorff rat hearts pretreated with YYH was measured. Incubation of isolated cardiac mitochondria with YYH and m PTP opening was measured. Results YYH 10 μL/m L can significantly improve ventricular function, ameliorate the level of myocardial tissue lesions. YYH(5 and 10 μL/m L) reduced CK and LDH release. And these protections were accompanied by a significant increase in p-PKB/Akt, p-ERK1/2, and p-GSK-3β(Ser-9). LY294002 abolished the protective effects of YYH on cardiac function and infarct size and inhibited YYH-induced phosphorylation of PKB/Akt and GSK-3β. MPTP opening in mitochondria isolated from YYH-pretreated occurred more readily invitro than I/R mitochondria. YYH(2.5, 5, 10, and 20 μL/m L), Shenmai injection(2.5, 5, 10, and 20μL/m L) resulted in a significant inhibition of Ca2+-induced mitochondrial swelling. Conclusion YYH produces direct cardioprotective actions. Inhibition of m PTP is a key event by which it mediates myocardial protection against I/R injury. And this effects involve activation of PI3K-Akt and ERK1/2 signal pathway. The mechanism of its action is different from that of Cs A.
【Fund】： “973”计划项目(2012CB518404);; 国家自然科学基金资助项目(81202779)
【CateGory Index】： R285.5
【CateGory Index】： R285.5