Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, 201 Sec- 2, Shih-Pai Road, Taipei, Taiwan.
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Cardiovasc Drugs Ther. 2021 Oct;35(5):889-900. doi: 10.1007/s10557-020-07072-z. Epub 2020 Sep 18.
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.
室性心律失常（VA）与炎症活动有关。红景天（RC）及其主要活性成分红景天苷已被报道为抗炎剂。本研究旨在通过抑制白细胞介素 17（IL-17）在缺血性心力衰竭（HF）模型中证明 RC 和红景天苷预防 VA 的作用。
通过冠状动脉结扎建立兔 HF 模型 4 周。这些兔子用 RC（125、250、500mg/kg）和红景天苷（9.5mg/kg）每 2 天治疗一次，共治疗 4 周。每 2 周测量白细胞（WBC）、血清生化、心电图和 CD4 T 细胞的表达。RC 和红景天苷治疗 4 周后，通过实时 PCR、ELISA 和 Western blot 测量 IL-17 的 mRNA 和蛋白表达。进行开胸心外膜导管刺激以引发 VA 诱发。
在 HF 左心室中用 RC 和红景天苷治疗后，（1）WBC 和 CD4 T 细胞水平下降，（2）IL-17 及其下游靶基因 IL-6、TNF-α、IL-1β、IL-8 和 CCL20 的表达减少，（3）NLRP3 炎性小体水平降低，（4）纤维化和胶原产生明显下调，（5）p38 MAPK 和 ERK1/2 磷酸化减弱，（6）VA 的诱导性降低，（7）Kir2.1、Nav1.5、NCX、PLB、SERCA2a 和 RyR 的水平升高。
RC 通过激活几种 MAPK 抑制 IL-17 及其下游靶基因的表达，降低纤维化和凋亡水平，并抑制 VA。
