Huoxue Qianyang Qutan recipe attenuates cardiac fibrosis by inhibiting the NLRP3 inflammasome signalling pathway in obese hypertensive rats

Autor: Deyu Fu, Mingtai Gui, Chen Xiaozhe, Bo Lu, Lei Yao, Mingyi Zhao, Xunjie Zhou, Jianhua Li, Jun Xie
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
obesity
Inflammasomes
Cardiac fibrosis
Interleukin-1beta
Pharmaceutical Science
Rats
Inbred WKY
Fibrosis
Rats
Inbred SHR
Drug Discovery
Angiotensin II
Caspase 1
Heart
General Medicine
Caspase Inhibitors
Hydroxyproline
Valsartan
Molecular Medicine
Hypertrophy
Left Ventricular
Myofibroblast
Research Article
Signal Transduction
medicine.drug
medicine.medical_specialty
hypertension
Primary Cell Culture
Context (language use)
RM1-950
Internal medicine
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Animals
Rats
Wistar
Cell Proliferation
Pharmacology
business.industry
Myocardium
medicine.disease
Rats
Endocrinology
Blood pressure
Complementary and alternative medicine
inflammation
traditional chinese medicine
Myocardial fibrosis
myocardial fibrosis
Therapeutics. Pharmacology
business
Drugs
Chinese Herbal
Zdroj: Pharmaceutical Biology, Vol 59, Iss 1, Pp 1045-1057 (2021)
Pharmaceutical Biology
article-version (VoR) Version of Record
ISSN: 1744-5116
1388-0209
Popis: Context HuoXue QianYang QuTan Recipe (HQQR) is used to manage hypertension and cardiac remodelling, but the mechanism is elusive. Objective To determine the mechanism of HQQR on obesity hypertension (OBH)-related myocardial fibrosis. Materials and methods OBH models were prepared using spontaneously hypertensive rats (SHRs) and divided (n = 6) into saline, low-dose (19.35 g/kg/d) HQQR, high-dose (38.7 g/kg/d) HQQR, and valsartan (30 mg/kg/d) groups for 10 weeks. Systolic blood pressure (SBP), and Lee’s index were measured. Heart tissues were examined by histology. HQQR’s effects were examined on cardiac fibroblasts (CFs) stimulated with angiotensin II and treated with HQQR, a caspase-1 inhibitor, siNLRP3, and oeNLRP3. Results HQQR(H) reduced SBP (201.67 ± 21.00 vs. 169.00 ± 10.00), Lee’s index (321.50 ± 3.87 vs. 314.58 ± 3.88), and left ventricle mass index (3.26 ± 0.27 vs. 2.71 ± 0.12) in vivo. HQQR reduced percentage of fibrosis area (18.99 ± 3.90 vs. 13.37 ± 3.39), IL-1β (10.07 ± 1.16 vs. 5.35 ± 1.29), and inhibited activation of NLRP3/caspase-1/IL-1β pathway. HQQR also inhibiting the proliferation (1.09 ± 0.02 vs. 0.84 ± 0.01), fibroblast to myofibroblast transition (14.74 ± 3.39 vs. 3.97 ± 0.53), and collagen deposition (Col I; 0.50 ± 0.02 vs. 0.27 ± 0.05 and Col III; 0.48 ± 0.21 vs. 0.26 ± 0.11) with different concentrations selected based on IC50 in vitro (all ps < 0.05). NLRP3 interference further confirmed HQQR inhibiting NLRP3 inflammasome signalling. Conclusion HQQR blunted cardiac fibrosis development in OBH and suppressed CFs proliferation by directly interfering with the NLRP3/caspase-1/IL-1β pathway.
Databáze: OpenAIRE
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