| Objective: To understand the dietary quality of patients with chronic obstructive pulmonary disease(COPD)and the prevalence of sarcopenia,analyze the dietary related risk factors of MDS,and explore the pathogenesis of MDS from the perspective of amino acid metabolites,so as to provide research basis for accurate prevention and targeted intervention of sarcopenia.Methods: 1)In the first part,a cross-sectional survey was conducted among 35-74 years old COPD patients recruited from Ili and Urumqi under the national key research and development program "Northwest regional natural population cohort study" sub project "Xinjiang Regional multi-ethnic natural population cohort construction and follow-up study",and questionnaire survey,physical measurement,body composition measurement and blood sample collection were carried out.Multivariate logistic regression analysis was used to calculate the area under receiver operating characteristic area(ROC)of each diagnostic model for validation.2)From the first part of the study,48 COPD patients with sarcopenia syndrome were selected as the case group,and 56 COPD patients without sarcopenia syndrome were selected as the control group.A case-control study design was adopted.Amino acid metabonomics was detected based on high performance liquid chromatography tandem mass spectrometry(UPLC-MC).Random forest method and partial least squares regression method were used to screen characteristic amino acid markers associated with sarcopenia.3)The second part of the screening of specific amino acid markers used reduced rank regression method to construct the dietary pattern and in vitro model experiment method to verify the effect of sarcopenia.Cell experiment method is to intervene mouse myoblasts with different concentrations of characteristic amino acids,evaluate cell proliferation activity,detect quality of m RNA of myoblasts proliferation activity marker protein and energy metabolism related proteins by RT-q PCR experiment,Western Blot experiment was used to detect the expression of these two proteins.Results: Part One: 1)672 COPD patients were included in the study.The dietary quality was investigated based on the dietary balance index(DBI-16),95.24% of the patients had inadequate dietary intake,98.21%of the patients had low to moderate dietary imbalance;B dietary pattern(mainly inadequate intake)accounted for the largest proportion(56.25%);91.52%,88.84%and 75.45%of the residents had inadequate intake of fish,shrimp,milk and vegetables;64.58%,55.80% and41.52%of the residents had inadequate intake of fruits,beans and food types.2)The prevalence of sarcopenia syndrome in COPD patients was 28.72%.3)Objective: Results of establishing a risk model for the effect of different dietary quality indicators on sarcopenia in COPD patients are: dietary type: low and excessive intake had a protective effect on sarcopenia(OR=0.650,95%CI: 0.425～0.994);dietary mode: B dietary mode was a risk factor for sarcopenia(OR=5.244,95%CI: 1.692～16.247).The specific food group:grains(OR=1.334,95%CI: 1.012～1.758),vegetables(OR=3.394,95%CI: 1.161～9.916),milk(OR=2.377,95%CI: 1.445～3.911),and food type(OR=2.933,95%CI: 1.588～5.417)were risk factors for sarcopenia.The AUC of the regression model validation of the above three indicators,that is,dietary type,dietary pattern and food group,on the influence of sarcopenia were 0.866,0.868 and 0.882,respectively.Inadequate dietary patterns and food types are common risk factors for sarcopenia and its parts.Part two: 1)Nine different amino acids were screened out(P<0.05)by the amino acid metabonomics detection,the expression of leucine and isoleucine was down regulated in the case group,while the expression of arginine,threonine,aspartate,histidine,tyrosine,lysine and valine was up-regulated in the case group.2)According to the random forest classification method,the top five variables with the highest importance score were BMI,valine,histidine,tyrosine and isoleucine.According to these five variables,the overall case group and the control group had the best differentiation,with the classification accuracy rate of 80.77%.3)Partial least squares regression analysis showed that the significant variables were BMI,valine,leucine and tyrosine(P<0.05).Any significant variables in the two models entered the model validation,which had good discrimination(AUC>0.70).Tyrosine and valine were the most important amino acids in the two models.Part 3: 1)The dietary pattern scores of tyrosine and valine were developed by the method of reduced rank regression,and the the dietary pattern is "low grain vegetable and bean products,high meat and edible oil".The dietary pattern score had a significant positive correlation with sarcopenia and low muscle mass and low walking speed,OR value is 2.053(95%CI:1.244～3.393),2.463(95%CI: 1.181～5.135),1.865(95%CI: 1.131～3.073)respectively.The AUC of Q3 was 0.942,which was better than that of the first part(P<0.05).2)The results of cell experiment in vitro showed that the proliferation activity of C2C12 myoblasts was decreased by different concentrations of tyrosine intervention.The results showed that the m RNA expression of cell proliferation marker protein Pax7 gradually decreased with the increase of concentration(P<0.05),and the m RNA expression of energy metabolism related proteins PGC-1α also showed a downward trend.The expression of Pax7 protein in high concentration group was the lowest,and the expression of PGC-1α protein in medium and high concentration group was the lowest.The proliferation activity of C2C12 cells was decreased by different concentrations of valine intervention.The maximum concentration group had the strongest inhibitory effect on Pax7 m RNA,and the medium and high concentration groups had the strongest inhibitory effect on Pax7 protein.The expression of PGC-1 α m RNA in the medium and high concentration group was the strongest,and the expression of PGC-1 α protein in the high concentration group was the strongest,which was higher than that in the positive control group(P<0.05).Conclusions: 1)The dietary is imbalance,and inadequate dietary patterns and insufficient food types are common risk factors of sarcopenia syndrome and multiple components among investigated COPD patients,which provides the latest evidence for precise dietary intervention strategy of sarcopenia.2)Valine and tyrosine are the important amino acid markers screened by multi model method,which is of great significance for the prediction,identification and development of new therapeutic targets and provide important clues to further explore the etiological mechanism.3)The metabolic markers of valine and tyrosine play an important role in the relationship between diet and sarcopenia syndrome.High concentration of tyrosine and valine inhibit the expression of proliferation related proteins and energy metabolism related proteins,which preliminarily verifies the etiological role of characteristic amino acids for sarcopenia syndrome and provides an important basis for its targeted intervention. |
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