| High altitude polycythemia(HAPC)is a chronic high altitude disease caused by hypoxia fundamentally,with red blood cells and blood viscosity increasing as its main signs.According to Tibetan Medicine,HAPC is a synthetical disease caused by inbalanced of Long,Tripa,Pekan,blood and dysfunctions,which belong to the category of Duoxie Zheng.Duoxuekang(DXK)capsule is based on clinical practice by Tibetan medicine master Cuoru Cailang.With main function of activating blood circulation to dissipate blood stasis and heat-clearing and detoxifying drugs,the DXK caspule is expert in treating Duoxue Zheng with curative effect.In our early recearch,it showed that the antioxidant activity of DXK caspule was strong,DXK caspule also could reduce blood stasis and lessen the symptoms of HAPC in rabbits,but the mechanism of action is unclear.What is the different of protein expression in brain tissue between the HAPC modle Rat and the normal ? How does DXK capsule affect the body at the molecular level during the process of intervention of HAPC ? To analyze the intercention mechanism of DXK capsule on HAPC,the topic is searching the differential proteins in different groups of rats with proteomics technology.Purpose:1.Clarifying the efficacy of DXK capsule in preventing and treating HAPC with the experiment of anti-hypoxia,anti-fatigue,nutritional health effects evaluation and anti-oxidation.2.Using Lable-free proteomic techniques to actualize the expression of protein in the brain tissue of HAPC model rats and which intervented by DXK capsule,analysising differentially expressed proteins in different groups of rats,to exploring the mechanism of the treatment of HAPC with DXK capsule from the molecular level.Methods:1.Pharmacodynamics experiment of DXK Capsule:(1)Effect of DXK capsule4 on hypoxia tolerance with atmospheric hypoxia experiment and sodium nitrite poisoning experiment.(2)Effect of DXK capsule on anti-fatigue with weight-bearing swimming experiment,content of lactic acid and liver glycogen.(3)Evaluation of the nutritional health effect of DXK capsule.(4)Experimental on antioxidant effect of HAPC modle rats treated by DXK capsule with the content of SOD,MDA and GSH-PX.2.Differential protein in the brain tissue of HAPC model rats treated by DXK capsule: The brain tissue of rats would be analysised with Lable-free proteomic techniques and platform of LC-MS spectrum,the analysis would contain hierarchical cluster analysis,differential protein GO classification,pathways and protein-protein interaction(PPI)network.At last,Western Blot would be used to verify the differentially expressed proteins to explore the mechanism of the molecular mechanism of HAPC in the treatment of DXK capsule.Results:1.The experiment of atmospheric hypoxia and sodium nitrite poisoning are positive factors of hypoxia tolerance experiment.The experiment of weight-bearing swimming experiment,content of lactic acid and liver glycogen are positive factors.the BDI index of health effect of spleen,kidney,pancreas and gonad were higher than1.DXK capsule can improve the SOD,MDA and GSH-PX indexes of HAPC model rats.2.19623 peptide sequences were identified by Lable-free proteomic method,which matched with the 2914 Unique proteins.161 differences were found between P-value <0.05 and fold change <0.40 or fold change> 1.60.The number of differentially expressed proteins between Plain control group and Plateau model group is 82,which between Drug therapy groups and Plateau model group is 155.Conclusions:1.DXK capsule has the effect of anti-hypoxia,anti-fatigue,anti-oxidation,and benefits and health effects.2.The Lable-free proteomic techniques can analyze the differences between different groups of protein,the characteristics of differences protein expressionbetween different groups and PPI network.The results suggest that the pathogenesis of HAPC and the molecular mechanism of HAPC by DXK capsule revealed on the blood system,energy metabolism,nervous system and oxidative stress. |
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