| Cardiovascular disease has been a serious threat to human health,with high morbidity and mortality,widely of which is myocardial ischemia.Most of the drugs used in clinical treatment are chemical drugs,which have their own pharmacological effects and mechanisms,of course,there are also some side effects.In addition to these chemical drugs,we should actively look for other drugs with good efficacy and minor side effects.Tibetan medicine is an intricate medicine with a long history of treatment effectiveness.Its comprehensive and flexible treatment strategies always bring about fantastic treatment result based upon herbal treatment.Tsantan Sumtang is a traditional Tibetan medicine,which consists of choerospondias axillaris(Roxb.)Burtt et Hill,Santalum album L,and Myristica fragrans Houtt.It is traditionally used as medicine for the treatment of cardiopyretic disease which is similar to angina.However,the precise and comprehensive mechanism of Tsantan Sumtang pretreatment remain elusive.And the previous studies usually focused on only one particular protein rather than multiple targets.By targeting multiple protein targets,Tibetan medicine exerts a synergistic therapeutic effect on the prevention and treatment of disease.The pharmacological effects and the mechanism is a result of many compounds through regulating biological molecular network.So only focus on the whole myocardial proteome,can it be to reveal the exact mechamism of Tsantan Sumtang on protecting myocardial ischemia.In this study,we first investigated the protective effects of Tsantan Sumtang on myocardial ischemia injury induced by left anterior descending coronary artery ligation in rats through serum biochemical and cardiac function parameters.Fourty-eight healthy rats were randomly divided into sham operation group(distilled water,10 ml·kg-1);Model group(distilled water,10 ml·kg-1);Positive drug group(0.3 g·kg-1);Tsantan Sumtang(0.5,1,2 g-kg-1 day for 20 days)group.Myocardial ischemia models were induced by left anterior descending coronaty artery ligation to test the hemodynamic parameters and the level of serum lactate dehydrogenase(LDH),creatine kinase(CK),Malodialdehyed(MDA),Superoxide Dismutase(SOD)activities.Results showed that in the model group,HR,LVSP and ±dp/dt decreased and LVEDP increased(P<0.05,P<0.01).When given Tsantan Sumtang,there was a amelioration in changes of systolic and diastolic function compared with model group.The high and middle dose of Tsantan Sumtang can improve the hemodynamic function and biochemical parameters compared with model group.So Tsantan Sumtang possessed protective effects on mycardial ischemia induced by left anterior descending coronaty artery ligation in rats.And then we used proteomics technology of high performance liquid chromatography(HPLC)-mass spectrometry(MS)using isobaric tandem mass tags(TMTs)to systematically analyse the protein expression.Rats were divided into three groups(n = 6):Tsantan Sumtang group(2 g·kg-1/day for 20 days),model group,and sham operation group(distilled water,10 ml·kg-1).The left anterior descending artery from the pulmonary conus to the left atrial appendage was ligated after the last administration of the drug,and the hearts of rats were harvested 5 days latter.Differentially expressed proteins were identified by proteomics.We identified 752 proteins to be differentially expressed in the model group compared to the control group.Of these,314 proteins were recovered by the Tsantan Sumtang treatment,most of which were metabolic enzymes,including glycolytic enzymes,enzymes implicated in fatty acid oxidation and tricarboxylic acid cycle,subunits of mitochondrial electron transfer chain complexes,as well as enzymes involved in antioxidation system.We paid more attention on phosphoglycerate mutase,6-phosphofructokinase,NADH-ubiquinone oxidoreductase(Complex I),cytochrome oxidase(Complex ?),creatine kinase and acetyl coenzyme A carboxylase 2.All these proteins were up-regulated in Tsantan Sumtang group.So Tsantan Sumtang can target and regulate multiple metabolic perturbed pathways.Importantly,it can partially inhibit fatty acid ?-oxidation and stimulate glucose metabolism,oxidative phosphorylation and ATP utilization.The results of this study may help us to better understand the molecular mechanisms of Tsantan Sumtang in the treatment of myocardial ischemia. |
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