Shenfu Injection improves chronic heart failure by regulating pyroptosis based on NLRP3/caspase-1 pathway.
10.19540/j.cnki.cjcmm.20230914.701
- Author:
Xing-Yu FAN
1
;
Xiao-Qian LIAO
1
;
Shu-Min HUANG
2
;
Zi-Yi WANG
1
;
Lin LI
1
;
Zhi-Xi HU
1
Author Information
1. College of Traditional Chinese Medicine,Hunan University of Chinese Medicine Changsha 410208,China.
2. College of Traditional Chinese Medicine,Hunan University of Chinese Medicine Changsha 410208,China the Second People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine Fuzhou 350003,China.
- Publication Type:Journal Article
- Keywords:
NLRP3;
Shenfu Injection;
caspase-1;
heart failure;
pyroptosis
- MeSH:
Rats;
Animals;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Pyroptosis;
Interleukin-18/metabolism*;
Caspase 1/metabolism*;
Stroke Volume;
Isoproterenol;
Ventricular Function, Left;
Heart Failure/drug therapy*;
Fibrosis;
Drugs, Chinese Herbal
- From:
China Journal of Chinese Materia Medica
2023;48(23):6475-6482
- CountryChina
- Language:Chinese
-
Abstract:
This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1β, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1β, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1β and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.
