title: Molecular Mechanisms of Increased Heart Rate in Shenxianshengmai-treated Bradycardia Rabbits.
abstract: BACKGROUND
  The molecular mechanisms of Shenxianshengmai (SXSM), a traditional Chinese medicine, on bradycardia have been incompletely understood. The study tried to investigate the gene expression profile and proteomics of bradycardia rabbits' hearts after SXSM treatment.
  
  
  METHODS
  Twenty-four adult rabbits were randomly assigned in four groups: sham, model, model plus SXSM treatment, and sham plus SXSM treatment groups. Heart rate was recorded in all rabbits. Then, total RNA of atria and proteins of ventricle were isolated and quantified, respectively. Gene expression profiling was conducted by gene expression chip, and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to confirm the results of gene expression chip. We used isobaric tags for elative and absolute quantitation and Western blotting to identify altered proteins after SXSM treatment.
  
  
  RESULTS
  There was a constant decrease in the mean heart rate (32%, from 238 ± 6 beats/min to 149 ± 12 beats/min) after six weeks in model compared with that in sham group. This effect was partially reversed by 4-week SXSM treatment. Complementary DNA microarray demonstrated that the increased acetylcholinesterase and reduced nicotinic receptor were take responsibility for the increased heart rate. In addition, proteins involved in calcium handling and signaling were affected by SXSM treatment. Real-time RT-PCR verified the results from gene chip. Results from proteomics demonstrated that SXSM enhanced oxidative phosphorylation and tricarboxylic acid (TCA) cycle in ventricular myocardium to improve ATP generation.
  
  
  CONCLUSIONS
  Long-term SXSM stimulates sympathetic transmission by increasing the expression of acetylcholinesterase and reduces the expression of nicotinic receptor to increase heart rate. SXSM also restored the calcium handling genes and altered genes involved in signaling. In addition, SXSM improves the ATP supply of ventricular myocardium by increasing proteins involved in TCA cycle and oxidation-respiratory chain.
authors.affiliation: State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037; Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Zhou-Ying
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Shandong Buchang Pharmaceutical Co. Ltd., Heze, Shandong 274003, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Shandong Buchang Pharmaceutical Co. Ltd., Heze, Shandong 274003, China.
authors.forename: Bu-Chang
authors.initials: BC
authors.lastname: Zhao
authors.affiliation: Shandong Buchang Pharmaceutical Co. Ltd., Heze, Shandong 274003, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Jie-Lin
authors.initials: JL
authors.lastname: Pu
mesh_terms: D000818:Animals; D001919:Bradycardia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D040901:Proteomics; D011817:Rabbits; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004365:Drugs, Chinese Herbal