麝香保心丸对STEMI患者心肌缺血再灌注损伤保护及其机制的研究

Reperfusion measures significantly reduce the mortality of patients with ST segment-elevated myocardial infarction (STEMI). But the reperfusion itself induced myocardial ischemia and reperfusion injury (MIRI), even causing an negative effect on the prognosis of patients with STEMI. At present, there is no a medicine to effectively treat MIRI. The etiopathogenesis of MIRI has the diversity. Shexiang Baoxin Pill (SBP) with multifarious etiopathogenesis is a chinese traditional medicine, which alleviated MIRI in animals with STEMI. Single photon emission computed tomography (SPECT) accurately assessed the extent of myocardial IRI in patients with STEMI. So, we will valuate the effect of SBP on myocardial protection against MIRI using SPECT. Oxidative stress and inflammation response participated in MIRI, and that their inhibition lead to protect myocardium against MIRI. In addition, SBP can inhibite the level of inflammatory factor and increase the level of superoxide dismutase (SOD). The phosphoinositide 3-kinase/threonine protein kinase (PI3K/Akt) pathway inhibited the myocardial apoptosis induced by IRI through elevating the level of nitric oxide synthase (eNOS). Meanwhile, SBP promoted gene expression of eNOS. Thus, we will explore the potential mechanism in the cardioprotection of SBP against MIRI: 1 the inhibition effect on oxidative stress and inflammation response induced by MIRI; 2 the depression effect on myocardial apoptosis caused by MIRI; 3 the possiblity that SBP protect myocardium by PI3K/Akt/ eNOS pathway.

再灌注治疗使STEMI患者病死率已明显下降，但诱发心肌缺血再灌注损伤(MIRI)，严重使患者预后差。目前没有对STEMI患者MIRI有效的治疗药物。MIRI发病机制具有多样性。麝香保心丸（SBP）是具有多样性作用的传统中药制剂，减轻动物MIRI。心肌ECT（SPECT）准确评价MIRI。因此，我们将用SPECT评价SBP对STEMI患者MIRI保护作用。氧化应激和炎性反应参与MIRI，而抑制其可保护心肌细胞。SBP抑制炎性因子，增加超氧化物歧化酶(SOD)水平。磷脂酰肌醇激酶-3/蛋白激酶B(PI3K/Akt)信号通路升高内皮型一氧化氮合酶(eNOS)水平，抑制IRI所致的心肌细胞调亡。SBP促进eNOS基因表达。因而，我们将研究SBP对MIRI保护机制：1.对MIRI氧化应激和炎性反应的抑制；2.对MIRI引起心肌细胞调亡的抑制3.是否通过PI3K/Akt/eNOS信号通路保护心肌

ST段抬高型心肌梗死（STEMI）是冠心病主要死亡原因。再灌注治疗可降低STIMI患者心肌梗死面积、心力衰竭发生率和病死率，但可诱发心肌缺血再灌注损伤(MIRI)，其可使最终心肌梗死面积明显增加，降低了再灌注治疗疗效。心肌梗死面积是STEMI患者预后的主要决定因子。但是，能够降低STEMI患者MIRI、减少心肌梗死面积有效治疗措施却很少，而且临床研究结果也不一致有效。因此，这些单一治疗措施对STEMI患者MIRI疗效不确切，使对MIRI治疗进入困境。MIRI具有多种发病机制，因此治疗MIRI有多种靶目标，不同靶目标治疗方法协同治疗可能取得更好疗效。麝香保心丸（SBP）是一种用于治疗冠心病的传统多种中药复方制剂，具有多种作用机制。因而我们研究SBP对STEMI患者MIRI、心肌梗死面积及预后影响。氧化应激和炎性反应是MIRI主要发病机制之一。SBP具有抑制氧化应激和炎性因子，促进升高eNOS 水平。磷脂酰肌醇激酶-3/蛋白激酶B(P13K/Akt)信号传导通路升高eNOS 水平，抑制MIRI 所致的心肌细胞调亡。因而，我们研究SBP对MIRI保护机制：SBP对MIRI氧化应激、炎性反应、心肌细胞调亡的抑制作用，是否通过P13K/Akt/eNOS信号通路保护心肌。.研究结果：1.SBP减轻STEMI患者MIRI（挽救心肌、挽救指数），降低心肌梗死面积（肌钙蛋白峰值、心肌梗死面积），改善心功能（NT-proBNP、射血分数），可改善患者预后，带来了明显社会效益。SBP可能成为治疗STEMI患者MIRI有效药物。2.SBP经PI3K/AKT/eNOS信号通路抑制氧化应激、细胞凋亡和炎性反应，减轻急性心肌梗死大鼠MIRI和心肌细胞缺血再灌注损伤。不仅能够证实SBP对MIRI多种作用机制，而且发现和完善MIRI发病机制，同时可证实作用于MIRI多种机制治疗的药物对MIRI治疗效果可能更好，也可为研制治疗MIRI治疗措施提供理论依据。