| PurposeChronic heart failure, a multiple organs and systems of the metabolic syndrome, is the final stage of various heart diseases. As the hub of human body metabolism and energy transformation, liver will certainly undergo pathological changes for venous congestion and artery ischemia hypoxia caused by chronic heart failure. At the same time, the heart and live.r physiology pathology determines the liver damage and there is some correlation between cardiac insufficiency. Qi is the subtle matter to maintain human life activities. Tonifying qi in traditional Chinese medicine plays a remarkable curative effect in the diagnosis and treatment of various diseases.Obverse the blood-breaking drug Si-Jun-Zi Decoction’s organizational pathological influences on the CVHI, ventricular remodeling, cardiac muscle tissue, lung tissue and liver tissue of rat with chronic heart failure, screen the differentially expressed protein before&after the intervention, and discuss its proteomic mechanism of action.MethodThis study includes two parts:literature research and experimental observation.First of all, in the literature study, the research progress of chronic heart failure and liver physiology and pathology are discussed to further prove hepatic passive congestion and hypoxia ischemia which is caused by chronic heart failure. At the same time, the liver damage and have certain relevance, cardiac insufficiency is one of the indicators of poor prognosis of chronic heart failure. Secondly, the five internal organs related theory of TCM and the "Chinese medicine spleen-mitochondria related","liver and spleen correlation" and "heart" of the doctrine of content, modern experiment research and clinical application are overviewed. Finally, the development of the technology of proteomics and bioinformatics and its application in the related diseases are reviewed.In the second part, the animal experiments,6out of42clean healthy male SD rats were saved as healthy group, other36were taken to copy the heart failed animal model by abdominal aortic constriction.8weeks later, the rat hemodynamic indexes were checked, and found LVEDP≥15mmHg, which shows that the heart failure model has successfully created. After that, those rats were randomly divided by Model group, Captopril group, high Si-Jun-Zi Decoction dose group and low Si-Jun-Zi Decoction dose group. After1month of regular feed, measure their LVEDP, HR, LVSP±dp/dt, kill them, take out their heart, lung and liver tissues, calculate the LVMI, RVMI, and observe the Histopathologic changes; isolate the protein of model and high Si-Jun-Zi Decoction dose group through Two-dimensional electrophoresis gel technology, twice for each group, and sort the differential protein through ImageMaster2D platinum5.0(GE), test the MS for peptide mass fingerprinting, check the protein name in NCBI database, GO analysis the molecule function, check the biological process, classify the cellular localization, find related pathway through KEGG.Results1. By abdominal aortic constriction method, the chronic heart failure rat model is created.2. The Si-Jun-Zi Decoction can obviously improve the rats’hemodynamic index (P<0.05) and ventriculus sinister re-construction (P<0.05), ease the lung and liver gore, and improve the heart function and the Histopathologic changes of ischemia hypoxia Lung and liver tissue.3.103differential proteins found on the rat livers of the two groups, among them49in Si-Jun-Zi Decoction group’s down shift,54in up shift. Select18typical differential proteins and conduct biological analysis, the results show that, after the Si-Jun-Zi Decoction intervention, the typical differential protein of liver tissue expression mainly take part in the internal chemical reaction, biological processes, organ development, stress reaction, metabolic process, biosynthesis, etc.; mainly catalyze the combination with other materials, mainly gathering at the material metabolic pathways.4. After the Si-Jun-Zi Decoction intervention, the proteins as follows obviously enhance the lever tissue expression:NADH dehydrogenase, Thyroid Hormone-Binding Proteins, Keratin, serpin, ethanol dehydrogenase, Haptoglobin precursor, Aromatic amine N-acetyl transferase, Estrogen sulfo transferase; and obviously weakened as follows:Calcium precursor protein, HMG-CoA synthetase, thione transferase and carboxylesterase. The proteins above are of critical importance in the function of liver. Results indicate that such blood-breaking Drugs can ease the damage of chronic heart failure on liver’s cell structure and function.ConclusionThis paper discusses the pathologic change caused by chronic heart failure, through the experiment that includes intervention of Si-Jun-Zi Decoction, a famous Chinese medicine, and the screening of the differential proteins by proteomics technology. The data and analysis results show:the Si-Jun-Zi Decoction can obviously improve the rats’heart function and’ventriculus sinister re-construction, ease the pathological change of lung and liver tissues with anoxia and ischemic; improve the synthesis of liver mitochondria related proteins which plays an important role in improving the vascular development and repair, adjusting neurohumoral endocrine system and curing CVD, and ATP synthesis; protect the liver cell structure from damage and improve the expression of functional protein’s liver metabolism, secretion, Detoxification, Endocrine, etc. In the meantime, such results develop the "spleen-mitochondria related CTM theories" raised by Professor Liu Youzhang, enrich the micro mechanism of heart-related theories, and provide the follow-up study with a new director and academic insight. |
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