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整合代谢组学和转录组学揭示瓜蒌薤白汤抗慢性心肌缺血的作用机制。

Integration of metabolomics and transcriptomics to reveal anti-chronic myocardial ischemia mechanism of Gualou Xiebai decoction.

机构信息

Pharmacy School, Hubei University of Chinese Medicine, Wuhan, 430065, China; Key Laboratory of Traditional Chinese Medicine Resource and Prescription, Ministry of Education, Wuhan, Hubei, 430061, China.

College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.

出版信息

J Ethnopharmacol. 2022 Oct 28;297:115530. doi: 10.1016/j.jep.2022.115530. Epub 2022 Jul 10.

DOI:10.1016/j.jep.2022.115530
PMID:35830899
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Gualou Xiebai decoction (GLXB), a well-known classic traditional Chinese medicine formula, is a recorded and proven therapy for the management of cardiac diseases. However, its pharmacological characteristics and mechanism of action are unclear.

MATERIALS AND METHODS

The effects of GLXB and its mechanism of action in an isoprenaline-induced rat model of chronic myocardial ischemia (CMI) were investigated by incorporating metabonomics and transcriptomics. Meanwhile, the echocardiographic evaluation, histopathological analysis, serum biochemistry assay, TUNEL assay and western blot analysis were detected to revealed the protective effects of GLXB on CMI.

RESULTS

The results of echocardiographic evaluation, histopathological analysis and serum biochemistry assay revealed that GLXB had a significantly cardioprotective performance by reversing echocardiographic abnormalities, restoring pathological disorders and converting the serum biochemistry perturbations. Further, the omics analysis indicated that many genes and metabolites were regulated after modeling and GLXB administration, and maintained the marked "high-low" or "low-high" trends. Meanwhile, the results from integrated bioinformatics analysis suggested that the interaction network mainly consisted of amino acid and organic acid metabolism. The results of TUNEL assay and western blot analysis complemented the findings of integrated analysis of metabolomics and transcriptomics.

CONCLUSION

These findings suggested that GLXB has a curative effect in isoproterenol-induced CMI in rats. Integrated analysis based on transcriptomics and metabolomics studies revealed that the mechanism of GLXB in alleviating CMI was principally by the regulation of energy homeostasis and apoptosis, which was through a multi-component and multi-target treatment modality.

摘要

民族药理学相关性

瓜蒌薤白汤(GLXB)是一种著名的经典中药方剂,被记录并证明可用于治疗心脏疾病。然而,其药理特性和作用机制尚不清楚。

材料和方法

通过代谢组学和转录组学研究,探讨 GLXB 及其在异丙肾上腺素诱导的慢性心肌缺血(CMI)大鼠模型中的作用机制。同时,进行超声心动图评估、组织病理学分析、血清生化分析、TUNEL 检测和 Western blot 分析,以揭示 GLXB 对 CMI 的保护作用。

结果

超声心动图评估、组织病理学分析和血清生化分析结果表明,GLXB 通过逆转超声心动图异常、恢复病理紊乱和转化血清生化紊乱,具有显著的心脏保护作用。此外,组学分析表明,建模和 GLXB 给药后许多基因和代谢物受到调节,并保持明显的“高-低”或“低-高”趋势。同时,综合生物信息学分析结果表明,相互作用网络主要由氨基酸和有机酸代谢组成。TUNEL 检测和 Western blot 分析结果补充了代谢组学和转录组学综合分析的结果。

结论

这些发现表明 GLXB 对异丙肾上腺素诱导的 CMI 大鼠具有治疗作用。基于转录组学和代谢组学研究的综合分析表明,GLXB 缓解 CMI 的机制主要是通过调节能量平衡和细胞凋亡,这是通过多成分和多靶点的治疗方式实现的。

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