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 DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats 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 matrixassisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins 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.
Scopus Subject Areas
- Complementary and alternative medicine
- Pharmacology (medical)
- Dingxin Recipe