主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

JOURNAL OF BEIJING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE ›› 2020, Vol. 43 ›› Issue (12): 995-1002.doi: 10.3969/j.issn.1006-2157.2020.12.005

• Chinese Medicinal Pharmocology • Previous Articles     Next Articles

Transcriptomics-based research on mechanism of Qishen Granule's regulatory effects on spleen ALOX15/STAT3 pathway to inhibit monocyte release and prevent heart failure*

Sun Xiaoqian1, Ma Lin2, Li Yanqin1, Lu Xiangyu3, Li Xuan1, He Hao2, Li Chun3#, Wang Yong1   

  1. 1 School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China;
    2 School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China;
    3 School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2020-07-15 Online:2020-12-30 Published:2021-01-05
  • Contact: Li Chun, Ph. D.,Associate Research Fellow, Master's Supervisor. School of Chinese Materia Medica,Beijing University of Chinese Medicine, Beijing 100029. E-mail: lichun19850204@163.com
  • Supported by:
    National Natural Science Foundation of China (No. 81673802)

Abstract: Objective To explore the expressions of the spleen monocyte mobilization-related proteins and pathways in heart failure based on transcriptomic data, and the mechanism of the regulatory effects of Qishen (Astragalus Root and Ginseng) Granule on such pathways. Methods Left anterior descending coronary artery ligation was used to establish the rat models of heart failure after myocardial infarction. The rats were randomly divided into the model group, the Qishen Granule (QSG) group, and the heart failure + spleen excision (splenectomy) group, and the sham operation group (SHAM). Rats in the QSG group were given Qishen Granule (235.2 mg/kg) by gavage for 21 days while the remaining groups were given the same volume of saline. Echocardiographic analysis was made on the rats in different groups to evaluate their cardiac function. RNA-seq technology at transcriptomic level and GO and KEGG pathway enrichment analysis were used to explore the expressions of genes in the spleen. Immunohistochemistry and Western blot were used to detect the distribution of splenic monocytes and the key proteins ALOX15, STAT3 and CCR2. Results Compared with the sham operation group, the left ventricular ejection fraction (LVEF) and short axis fractional shortening (LVFS) were significantly decreased (P<0.01), and the left ventricular diastolic internal diameters (LVID;d) and left ventricular systolic internal diameters (LVID;s) of the model group were significantly increased (P<0.01). Compared with the model group, the LVEF value of the splenectomy group was significantly increased (P<0.01), and the LVEF value of the QSG group was also significantly increased (P<0.05). Transcriptomic results identified 34 differential genes that QSG could regulate. The enrichment analysis of GO and KEGG pathways showed that the above genes were mainly enriched in such biological processes as immune regulation of spleen, leukocyte migration, and antigen processing and presentation. The expressions of CD163 and CD68 of the model group were significantly lower than those of the sham operation group (P<0.01); the expressions of CD163 and CD68 in the QSG group were significantly higher than those of the model group (P<0.05). Compared with the sham operation group, the expressions of STAT3 and CCR2 proteins increased and those of ALOX15 proteins decreased in the model group, and the expressions of STAT3 and CCR2 proteins decreased while those of ALOX15 proteins increased in the QSG group (P<0.01). Conclusion QSG can improve heart function and prevent and treat heart failure by regulating ALOX15/STAT3 pathway-mediated mobilization and release of splenic monocytes.

Key words: Qishen Granule, heart failure, monocyte release, transcriptomics, ALOX15, rats

CLC Number: 

  • R285.5