Dingxin recipe ( ) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses.

Abstract

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.

• Authors: Yu-Hua Jia, Yun-Xian Zhang, Li-Jun Li, Ya-Wei Liu, Chun-Hua Li, Xiu-Qiong Fu, Ping Zeng, Wei-Kang Wu, Xue-Gang Sun
• Journal: Chinese journal of integrative medicine (Chin J Integr Med) Vol. 18 Issue 2 Pg. 120-9 (Feb 2012) ISSN: 1672-0415 [Print] China
• PMID: 22311408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• FABP3 protein, rat
• Fatty Acid Binding Protein 3
• Fatty Acid-Binding Proteins
• Interleukin-6
• Phb protein, rat
• Prohibitins
• Repressor Proteins
• dingxin
• Glutathione

Topics

• Animals
• Arrhythmias, Cardiac (etiology, prevention & control)
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Electrophoresis, Gel, Two-Dimensional
• Fatty Acid Binding Protein 3
• Fatty Acid-Binding Proteins (metabolism)
• Glutathione (metabolism)
• Heart Ventricles (drug effects, metabolism, pathology)
• Immunohistochemistry
• Inflammation (complications, metabolism, pathology)
• Interleukin-6 (metabolism)
• Male
• Myocardial Infarction (complications, drug therapy, pathology)
• Neutrophil Infiltration (drug effects)
• Peptide Mapping
• Prohibitins
• Proteomics
• Rats
• Rats, Wistar
• Reperfusion Injury (complications)
• Repressor Proteins (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Spectrophotometry
• Up-Regulation (drug effects)