Dingxin recipe ( ) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses.
OBJECTIVE
To identify the underlying mechanisms of the protective effects of Dingxin Recipe (: , DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model.


METHODS
A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments.


RESULTS
DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment.


CONCLUSIONS
DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.
The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Yu-Hua
YH
Jia
Yun-Xian
YX
Zhang
Li-Jun
LJ
Li
Ya-Wei
YW
Liu
Chun-Hua
CH
Li
Xiu-Qiong
XQ
Fu
Ping
P
Zeng
Wei-Kang
WK
Wu
Xue-Gang
XG
Sun
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D015180:Electrophoresis, Gel, Two-Dimensional; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010449:Peptide Mapping; D000091402:Prohibitins; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D012097:Repressor Proteins / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013053:Spectrophotometry; D015854:Up-Regulation / Q000187:drug effects
D004365:Drugs, Chinese Herbal; C509948:FABP3 protein, rat; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D015850:Interleukin-6; C000717332:Phb protein, rat; D000091402:Prohibitins; D012097:Repressor Proteins; C574801:dingxin; D005978:Glutathione