0301 basic medicine, MAPK/ERK pathway, MAP Kinase Signaling System, p38 mitogen-activated protein kinases, Anti-Inflammatory Agents, Stimulation, 030204 cardiovascular system & hematology, Pharmacology, Electrocardiography, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glucosides, Phenols, Fibrosis, NLR Family, Pyrin Domain-Containing 3 Protein, Rhodiola, Animals, Medicine, Pharmacology (medical), RNA, Messenger, Chemokine CCL20, Dose-Response Relationship, Drug, biology, business.industry, Interleukin-17, Salidroside, Arrhythmias, Cardiac, General Medicine, medicine.disease, biology.organism_classification, CD4 Lymphocyte Count, Disease Models, Animal, Drug Combinations, 030104 developmental biology, chemistry, Apoptosis, Rabbits, Interleukin 17, Inflammation Mediators, Cardiology and Cardiovascular Medicine, business, and Signal Transduction
Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model. Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4+ T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation. After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4+ T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1β, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated. RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA.