刘娜娜
中国医学科学院阜外医院 心律失常与电生理诊治中心
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.
Chinese medical journal 2017
Right ventricular apical (RVA) pacing can lead to progressive left ventricular dysfunction and heart failure (HF), even in patients with normal cardiac structure and function. Our study conducted candidate gene screening and lentivirus transfected neonatal rat cardiomyocytes (NRCMs) to explore the genetic and pathogenic mechanisms of RVA pacing induced cardiomyopathy in third degree atrioventricular block (III AVB) patients. We followed 887 III AVB patients with baseline normal cardiac function and RVA pacing. After a median follow-up of 2.5 years, 10 patients (four males, mean age 47.6 ± 10.0 years) were diagnosed with RVA pacing induced HF with left ventricular ejection fraction (LVEF) reducing dramatically to 37.8 ± 7.1% (P < 0.05). Candidate genes sequencing found cardiomyopathy associated genetic variations in all ten HF patients and six SCN5A variations in 6 of 20 control patients. Transfected NRCMs of Lamin A/C mutations (R216C and L379F) disrupted Lamin A/C location on nucleus membrane and finally resulted in increased apoptotic rate after serum starvation. In conclusion, cardiomyopathy associated genetic variations play an essential role in occurrence of newly onset HF in the III AVB patients with RVA pacing. RVA pacing, serving as extra stimulator, might accelerate the deterioration of cardiac structure and function.
Scientific reports 2017
Aims. The molecular mechanisms of Chinese traditional medicine Wenxin Keli (WXKL) were unknown. This study was aimed at exploring the effects of WXKL on the gene expression profile and pathological alteration of rabbits with myocardial infarction. Methods. Twenty male adult rabbits were randomly divided into 4 groups: sham, model, WXKL, and captopril groups. Model, WXKL, and captopril groups underwent the ligation of the left anterior descending coronary artery while sham group went through an identical procedure without ligation. WXKL (817 mg/kg/d), captopril (8 mg/kg/d), and distilled water (to model and sham groups) were administered orally to each group. After 4 weeks, the rabbits were examined with echocardiography and the hearts were taken for expression chip and pathological staining (H&E, Masson, and Tunel) studies. Results. The data revealed that WXKL downregulated genes associated with inflammation (CX3CR1, MRC1, and FPR1), apoptosis (CTSC and TTC5), and neurohumoral system (ACE and EDN1) and upregulated angiogenesis promoting genes such as RSPO3. Moreover, the results also showed that WXKL improved cardiac function and prevented histopathological injury and apoptosis. Conclusion. The present study demonstrated that WXKL might play an important role in inhibiting inflammation, renin-angiotensin system, and apoptosis. It might be a promising Chinese medicine in the treatment of patients with myocardial infarction.
Evidence-based complementary and alternative medicine : eCAM 2016
