The mechanism of ShengMaiSan reducing calcium leak and protecting myocardial contractile function in diabetic rats based on network pharmacology
10.16438/j.0513-4870.2022-0482
- VernacularTitle:基于网络药理学探讨生脉散降低钙泄漏保护糖尿病大鼠心肌收缩功能的机制研究
- Author:
Cong HUANG
1
;
Ming-jie SUN
1
;
Hai-feng CUI
1
;
Li-hua SUN
1
;
QIAN WU
1
;
Qu ZHAI
2
;
Xiao-lu SHI
1
Author Information
1. Key Laboratory of TCM Basic Research on Prevention and Treatment of Major Disease, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
2. National Medical Products Administration Institute of Executive Development, Beijing 100073, China
- Publication Type:Research Article
- Keywords:
ShengMaiSan;
iabetic cardiomyopathy;
calcium transport;
calcium leak;
network pharmacology
- From:
Acta Pharmaceutica Sinica
2022;57(10):3115-3123
- CountryChina
- Language:Chinese
-
Abstract:
In this study, network pharmacology research and animal experiments were used to predict and validate the potential targets of ShengMaiSan (SMS) in the treatment of diabetic cardiomyopathy. The active components of SMS were obtained through TCMSP and BATMAN databases. The potential targets of the active components and diabetic cardiomyopathy were predicted by Swiss Target Prediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to perform topological analysis to select the core action target. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using Metascape platform. To validate the potential targets, a type I diabetic rat model which induced by intraperitoneal injection of streptozotocin (STZ) was prepared. Rats were divided into sham group, model group, SMS group and trimetazidine (TMZ) group. Left ventricular hemodynamics was detected after 4 weeks administrated of SMS or TMZ. Myocardial contraction and calcium transients were detected synchronously in cardiomyocytes, as well as sarcoplasmic reticulum calcium content, calcium leak level and ryanodine receptor 2 (RyR2) expression were detected. Based on network pharmacology, 1 288 targets of SMS, 1 066 targets of diabetic cardiomyopathy, and 180 overlapped targets were obtained. The 39 core targets were screened, and 159 pathways including calcium signaling pathway were screened by KEGG pathway analysis. According to the previous studies and focusing on the contractility of diabetic cardiomyopathy, this study was involved calcium signaling regulation pathway in the SMS protection mechanism. The results showed that, compared with sham group, the systolic function of left ventricular and myocardial cells were decreased, and the calcium transport was in disorder in model group; compared with model group, both SMS group and TMZ group increased the maximum systolic pressure of left ventricle and the maximum systolic rate of left ventricular contraction. In addition, SMS group and TMZ group increased the contraction amplitude of cardiomyocytes, decreased the diastolic calcium concentration, the sarcoplasmic reticulum calcium leak and decreased the phosphorylation level of RyR2. There was no significant difference between SMS and TMZ groups. In summary, SMS could reduce the calcium leak of the sarcoplasmic reticulum and enhance the myofilament sensitivity of calcium to increasing contractile function of diabetic rats. The animal welfare and experiment procedures of this study were in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences.
