ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Animals , Male , Rats , Arrhythmias, Cardiac , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Electrophoresis, Gel, Two-Dimensional , Fatty Acid Binding Protein 3 , Fatty Acid-Binding Proteins , Metabolism , Glutathione , Metabolism , Heart Ventricles , Metabolism , Pathology , Immunohistochemistry , Inflammation , Metabolism , Pathology , Interleukin-6 , Metabolism , Myocardial Infarction , Drug Therapy , Pathology , Neutrophil Infiltration , Peptide Mapping , Proteomics , Rats, Wistar , Reperfusion Injury , Repressor Proteins , Metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Spectrophotometry , Up-RegulationABSTRACT
By reviewing pertinent literatures, we found that there existed some defects in studying material base on Chinese medical theory of "Fei and Dachang being interior-exteriorly related", such as the low efficacy of research methods; the neglect of intestinal and respiratory microhabitat and Chinese medical functional condition; and the unconformity of research design with evidence-based medicinal requirements. Thereby, the authors offered that the researches method of initiating merely from sole material or line linkage path should be rejected. The new research strategy should be established based on the feature of the lung and large intestine network connective structure, cutting-in from correlative changes in the two terminals (respiratory system and intestinal tissue), and the intermedial key knot of connection (blood serum), screen out in high throughput the relevant materials adopting microecological, proteomic and metabonomic techniques, and catch hold of the knots of network as much as possible. Based on these to perfect the researches on coordinating mechanism of the network, and to establish a new strategy for future researching.