OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease ...OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months,and the changes of cardiac function were observed.61 serum samples(including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group)were analyzed by non labeled proteomics.The disease group was used as the control group,and the protein with expression level difference of more than 1.2 folds(P<0.05)was screened.The molecular function,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction,regulate blood glucose and blood lipid levels,prolong thrombin time,and improve heart function.The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group.Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1,alpha-2 and other proteins to act on HDL assembly,platelet degradation,PI3K Akt signaling pathway,and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome.CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syndrome of coronary heart disease.It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins.This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.展开更多
心梗超急性期是指心梗发生后30 min内,症状不明显、诊断困难的一段时间,相关病理生理机制研究关注较少。本研究基于蛋白质组学探讨心梗超急性期蛋白质组改变并针对热休克蛋白B6(heat shock protein B6HSPB6)探讨注射用丹参多酚酸盐的干...心梗超急性期是指心梗发生后30 min内,症状不明显、诊断困难的一段时间,相关病理生理机制研究关注较少。本研究基于蛋白质组学探讨心梗超急性期蛋白质组改变并针对热休克蛋白B6(heat shock protein B6HSPB6)探讨注射用丹参多酚酸盐的干预作用与相关机制,为心梗超急性期病理机制及注射用丹参多酚酸盐的临床合理用药提供实验依据。采用基于质谱的非标记蛋白质组学对比评价大鼠心梗模型造模前后蛋白表达变化后,使用生物信息学方法分析共有表达蛋白及相关通路。接着运用分子对接技术评价注射用丹参多酚酸盐对共有差异蛋白HSPB6的结合作用,最后通过动物实验进行验证。本实验动物福利和实验过程均遵循中国中医科学院西苑医院实验动物伦理委员会的规定。本实验结果表明,非标记蛋白质组学结果共定量获得2166个蛋白质,其中有194个共有差异蛋白参与心梗超急性期心肌损伤和机体调节,主要涉及蛋白质同源二聚活性、氧气结合与运输、丝氨酸型内肽酶抑制剂活性等分子功能。其中,HSPB6蛋白参与心肌功能的调节作用。分子对接结果表明,注射用丹参多酚酸盐主成分丹参乙酸镁与HSPB6蛋白具有最低的结合能:-14.53 kcal·moL^(-1)。动物实验表明,与假手术组相比,模型组大鼠心功能损伤射血分数和短轴缩短率显著降低(P<0.001),心脏血流灌注明显下降(P<0.001),存在明显心肌纤维紊乱、心肌细胞水肿、间质内小血管充血等病理形态改变;给药组大鼠心功能损伤减弱,其中低剂量短轴缩短率明显改善(P<0.05),心肌组织病理性损伤明显减轻,HSPB6蛋白表达不同程度上调(P<0.01,P<0.001)。基于上述研究结果,发现注射用丹参多酚酸盐可一定程度改善大鼠心梗超急性期损伤心功能及病理形态,其作用机制可能与促进HSPB6表达有关。展开更多
基金National Natural Science Foundation of China(82030124)and National Key Basic Research Special Foundation of China(2015CB554400)。
文摘OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months,and the changes of cardiac function were observed.61 serum samples(including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group)were analyzed by non labeled proteomics.The disease group was used as the control group,and the protein with expression level difference of more than 1.2 folds(P<0.05)was screened.The molecular function,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction,regulate blood glucose and blood lipid levels,prolong thrombin time,and improve heart function.The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group.Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1,alpha-2 and other proteins to act on HDL assembly,platelet degradation,PI3K Akt signaling pathway,and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome.CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syndrome of coronary heart disease.It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins.This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.