title: Qishenyiqi protects ligation-induced left ventricular remodeling by attenuating inflammation and fibrosis via STAT3 and NF-κB signaling pathway.
abstract: OBJECTIVE
  Qi-shen-yi-qi (QSYQ), a formula used for the routine treatment of heart failure (HF) in China, has been demonstrated to improve cardiac function through down-regulating the activation of the Renin-Angiotensin-Aldosterone System (RAAS). However, the mechanisms governing its therapeutic effects are largely unknown. The present study aims to demonstrate that QSYQ treatment can prevent left ventricular remodeling in heart failure by attenuating oxidative stress and inhabiting inflammation.
  
  
  METHODS
  Sprague-Dawley (SD) rats were randomly divided into 6 groups: sham group, model group (LAD coronary artery ligation), QSYQ group with high dosage, middle dosage and low dosage (LAD ligation and treated with QSYQ), and captopril group (LAD ligation and treated with captopril as the positive drug). Indicators of fibrosis (Masson, MMPs, and collagens) and inflammation factors were detected 28 days after surgery.
  
  
  RESULTS
  Results of hemodynamic alterations (dp/dt value) in the model group as well as other ventricular remodeling (VR) markers, such as MMP-2, MMP-9, collagen I and III elevated compared with sham group. VR was accompanied by activation of RAAS (angiotensin II and NADPHoxidase). Levels of pro-inflammatory cytokines (TNF-α, IL-6) in myocardial tissue were also up-regulated. Treatment of QSYQ improved cardiac remodeling through counter-acting the aforementioned events. The improvement of QSYQ was accompanied with a restoration of angiotensin II-NADPHoxidase-ROS-MMPs pathways. In addition, "therapeutic" QSYQ administration can reduce both TNF-α-NF-B and IL-6-STAT3 pathways, respectively, which further proves the beneficial effects of QSYQ.
  
  
  CONCLUSIONS
  Our study demonstrated that QSYQ protected LAD ligation-induced left VR via attenuating AngII -NADPH oxidase pathway and inhabiting inflammation. These findings provide evidence as to the cardiac protective efficacy of QSYQ to HF and explain the beneficial effects of QSYQ in the clinical application for HF.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Basic Medical College, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Anzhen Hospital of Capital Medical University, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Basic Medical College, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Shi
authors.affiliation: Basic Medical College, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Basic Medical College, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Xingyun
authors.initials: X
authors.lastname: Chai
authors.affiliation: Basic Medical College, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008026:Ligation / Q000009:adverse effects; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D016328:NF-kappa B; D020011:Protective Agents; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D000804:Angiotensin II; D002216:Captopril; D019255:NADPH Oxidases; D020782:Matrix Metalloproteinases