Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies.
10.1007/s11655-023-3633-0
- Author:
Ya-Fang TAN
1
;
Yu-Han FU
2
;
Min-Zhou ZHANG
3
Author Information
1. Intensive Care Research Team of Traditional Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
2. School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
3. Intensive Care Research Team of Traditional Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. minzhouzhang8@163.com.
- Publication Type:Journal Article
- Keywords:
RNA-seq;
Shexiang Tongxin Dropping Pill;
extracellular matrix;
heart failure;
isoproterenol-induced
- MeSH:
Rats;
Animals;
Matrix Metalloproteinase 2/metabolism*;
Matrix Metalloproteinase 9/metabolism*;
RNA-Seq;
Transcriptome/genetics*;
Heart Failure/drug therapy*;
Collagen;
Collagen Type I/metabolism*;
Fibrosis;
Myocardium/pathology*
- From:
Chinese journal of integrative medicine
2023;29(7):600-607
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF).
METHODS:Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting.
RESULTS:The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs.
CONCLUSIONS:STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.
