| The first part of this paper is the proteomic analysis of the cardioprotective effect of Shexiang Baoxin Pill(SBP).Cardiovascular disease has the highest morbidity and mortality among the four major noncommunicable diseases in the world.Since its approvement in 1982,SBP has been widely proved that it has good efficacy and safety in the treatment of coronary heart disease and myocardial infarction(MI),and is currently the most common Chinese medicine used in the treatment of cardiovascular diseases in China.However,the pharmacologic mechanism of SBP in the treatment of cardiovascular diseases has not been clearly elucidated.Therefore,we applied proteomic approach to study the cardioprotective effect of SBP in the treatment of MI model rats.First,through cooperation we analyzed the echocardiography of MI model rats,and found that the left ventricular fractional shortening and ejection fraction of MI rats treated with SBP were significantly improved,indicating that their cardiac function was restored.Then,the heart tissues of MI rats treated with SBP was analyzed through massspectrometry-based quantitative proteomic technique,where differentially expressed proteins was systematically identified,and 15 proteins closely related to cardiovascular disease were found among them.Functional enrichment analysis of differentially expressed proteins found that SBP treatment significantly upregulated proteins that are involved in cellular mitochondrial energy metabolism processes in the heart of MI rats,including fatty acid metabolism,redox process,and aerobic respiration process.Through western blot analysis,we validated that two differentially expressed proteins involved in energy metabolism,fatty acid binding protein 3 and myoglobin,were downregulated in the heart of MI rats,but upregulated after SBP treatment.This part of work interpreted the cardioprotective effect of SBP in MI rats from the perspective of proteomics,showing that SBP may achieve cardioprotective effect by improving the energy metabolism related pathways in cardiomyocytes.The second part of this paper is the proteomic analysis of the potential function of fructose diphosphate aldolase A(ALDOA)in liver cancer development.Liver cancer is the third most deadly cancer in China,with the characteristics of early detection difficulty,rapid progression,low five-year survival rate of patients.In 2020 alone the number of deaths due to liver cancer nationwide reached 390,000,but there is still a lack of liver cancer targeted drugs with significant efficacy.Therefore,it is urgent to develop new therapeutic targets for liver cancer treatment.We reanalyzed the proteomic data of the clinical cohort of liver cancer and found that ALDOA is a poor prognostic factor for patients.Besides,we found that ALDOA knockdown suppressed the proliferation and promoted the apoptosis of liver cancer cells,which showed that ALDOA might become a potential therapeutic target for liver cancer.Then,we applied data independent acquisition(DIA)technique to analyze the proteome of ALDOA-knocked-down Huh-7 cells,resulting in more than 8,000 proteins quantified.Data analyses showed that ALDOA knockdown might upregulate the expression of the AMPK complex in Huh-7 cells,resulting in down regulation of the downstream transcription factor SREBP1 and the decrease of most key metabolic enzymes in cellular fatty acid metabolism and cholesterol metabolism. |
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