摘要
Objective： To identify the underlying mechanisms of the protective effects of Dingxin Recipe （定心方, 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- I/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 matrix- assisted 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 （RQ- PCR）, 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.
Objective： To identify the underlying mechanisms of the protective effects of Dingxin Recipe （定心方, 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- I/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 matrix- assisted 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 （RQ- PCR）, 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.
基金
Supported by the National Natural Science Foundation of China (No.30572435 and No.81072776)
Baiyun District Science and Technology Program(No.2010-KZ-39)
