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蛋白质组学分析揭示益气复脉冻干注射剂通过改善心肌能量代谢对慢性心力衰竭的保护作用。

Proteomic Analysis Reveals the Protective Effects of Yiqi Fumai Lyophilized Injection on Chronic Heart Failure by Improving Myocardial Energy Metabolism.

作者信息

Han Xiaoying, Zhang Yi, Qiao Ou, Ji Haixia, Zhang Xinyu, Wang Wenzhe, Li Xia, Wang Juan, Li Dekun, Ju Aichun, Liu Changxiao, Gao Wenyuan

机构信息

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Tasly Pride Pharmaceutical Company Limited, Tianjin, China.

出版信息

Front Pharmacol. 2021 Sep 21;12:719532. doi: 10.3389/fphar.2021.719532. eCollection 2021.

Abstract

Yiqi Fumai lyophilized injection (YQFM) is the recombination of Sheng mai san (SMS).YQFM has been applied clinically to efficaciously and safely treat chronic heart failure (CHF). However, the mechanism of YQFM is still not fully elucidated. The purpose of our study was to investigate the protective mechanism of YQFM against abdominal aortic coarctation (AAC) in rats by proteomic methods. After YQFM treatment, the cardiac function were obviously meliorated. One hundred and fifty-seven important differentially expressed proteins (DEPs) were identified, including 109 in model rat compared with that in control rat (M:C) and 48 in YQFM-treated rat compared with that in model rat (T:M) by iTRAQ technology to analyze the proteomic characteristics of heart tissue. Bioinformatics analysis showed that DEPs was mainly involved in the body's energy metabolism and was closely related to oxidative phosphorylation. YQFM had also displayed efficient mitochondrial dysfunction alleviation properties in hydrogen peroxide (HO)-induced cardiomyocyte damage by Transmission Electron Microscope (TEM), Metabolic assay, and Mitotracker staining. What's more, the levels of total cardiomyocyte apoptosis were markedly reduced following YQFM treatment. Furthermore, Western blot analysis showed that the expressions of peroxisome proliferator activated receptor co-activator-1α(PGC-1α) ( < 0.01 or < 0.001), perixisome proliferation-activated receptor alpha (PPAR-α) ( < 0.001)and retinoid X receptor alpha (RXR-α) were upregulated ( < 0.001), PGC-1α as well as its downstream effectors were also found to be upregulated in cardiomyocytes after YQFM treatment( < 0.001).These results provided evidence that YQFM could enhance mitochondrial function of cardiomyocytes to play a role in the treatment of CHF by regulating mitochondrial biogenesis-related proteins.

摘要

益气复脉冻干注射剂(YQFM)是生脉散(SMS)的重组方。YQFM已在临床上用于有效且安全地治疗慢性心力衰竭(CHF)。然而,YQFM的作用机制仍未完全阐明。我们研究的目的是通过蛋白质组学方法研究YQFM对大鼠腹主动脉缩窄(AAC)的保护机制。YQFM治疗后,心功能明显改善。通过iTRAQ技术鉴定出157种重要的差异表达蛋白(DEP),包括模型大鼠与对照大鼠相比(M:C)的109种以及YQFM治疗大鼠与模型大鼠相比(T:M)的48种,以分析心脏组织的蛋白质组学特征。生物信息学分析表明,DEP主要参与机体能量代谢,与氧化磷酸化密切相关。通过透射电子显微镜(TEM)、代谢分析和线粒体追踪染色,YQFM在过氧化氢(HO)诱导的心肌细胞损伤中也表现出有效的线粒体功能障碍缓解特性。此外,YQFM治疗后心肌细胞总凋亡水平明显降低。此外,蛋白质免疫印迹分析表明,过氧化物酶体增殖物激活受体共激活因子-1α(PGC-1α)(<0.01或<0.001)、过氧化物酶体增殖激活受体α(PPAR-α)(<0.001)和视黄酸X受体α(RXR-α)的表达上调(<0.001),YQFM治疗后心肌细胞中PGC-1α及其下游效应物也上调(<0.001)。这些结果提供了证据,表明YQFM可通过调节线粒体生物发生相关蛋白增强心肌细胞的线粒体功能,从而在CHF治疗中发挥作用。

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