Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue ...Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue samples from normal and high-fat diet(HFD)fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses.In the animal experiments,mice were randomly divided into the control(N),high-calorie diet pneumonia(M),and Yinlai decoction treatment(Y)groups.Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d.The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d.Pathological evaluation of the lung tissue was performed.Differentially expressed proteins(DEPs)in the lung tissue were identified using quantitative proteomics and bioinformatics analyses.The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory(MGL)Tools.DEPs were verified by western blot.Results:GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue.The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet.A total of 47 DEPs were identified between the Y and M groups.Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle(TCA)and oxidative phosphorylation.The protein-protein interaction network revealed that Atp5a1,Pdha1,and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction.Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide,praeruptorin B,chrysoeriol,and other components in Yinlai decoction to Atp5a1.Conclusion:The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation.Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.展开更多
Objective:To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet,as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction(YD)and its ef...Objective:To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet,as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction(YD)and its effects on inflammation-related metabolic pathways.Methods:Lipopolysaccharides(LPS)and a special high-calorie diet were used to induce Sprague Dawley(SD)rats to simulate the intestinal state of infant pneumonia.Liquid chromatography-mass spectrometry technology(LC-MS/MS)was used to detect metabolites in each group.Supervised orthogonal partial least squares discriminant analysis(OPLS-DA)model values were used for the detection results to find the differential metabolites.The metabolic pathways that are involved with the differential metabolites were clarified through enrichment analysis and topological analysis.Finally,the T cell receptor signaling pathway(TCR)signal conversion was analyzed by the network pharmacology method.Results:In the high-calorie diet combined with pneumonia group(M3),a total of 55 metabolites were determined to be different from the normal group(N).A total of 36 metabolites were determined to be different from those in the lung metabolites of the YD treatment group(T1).YD had a regulatory effect on glutathione metabolism,arginine and proline metabolism,ascorbic acid and aldehyde metabolism and phenylalanine metabolism.And the small molecule metabolites could act on the FYN and lymphocytespecific protein tyrosine kinase(LCK)target proteins in the TCR signaling pathway,thereby affecting the immune function of the lungs.Conclusion:A high-calorie diet can cause abnormal sphingolipid metabolism in the lungs of young rats,thereby creating chronic lung inflammation in young rats.YD has a beneficial effect when used to treat young rats with LPS-induced pneumonia fed on high-calorie diets.Its mechanisms of action may affect the body’s immune pathways by regulating the oxidative stress pathway affected by glutathione metabolism.展开更多
基金supported by the National Natural Science Foundation of China(81874421)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202006).
文摘Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue samples from normal and high-fat diet(HFD)fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses.In the animal experiments,mice were randomly divided into the control(N),high-calorie diet pneumonia(M),and Yinlai decoction treatment(Y)groups.Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d.The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d.Pathological evaluation of the lung tissue was performed.Differentially expressed proteins(DEPs)in the lung tissue were identified using quantitative proteomics and bioinformatics analyses.The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory(MGL)Tools.DEPs were verified by western blot.Results:GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue.The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet.A total of 47 DEPs were identified between the Y and M groups.Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle(TCA)and oxidative phosphorylation.The protein-protein interaction network revealed that Atp5a1,Pdha1,and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction.Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide,praeruptorin B,chrysoeriol,and other components in Yinlai decoction to Atp5a1.Conclusion:The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation.Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.
基金This work was supported by the National Natural Science Foundation of China(8187150612).
文摘Objective:To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet,as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction(YD)and its effects on inflammation-related metabolic pathways.Methods:Lipopolysaccharides(LPS)and a special high-calorie diet were used to induce Sprague Dawley(SD)rats to simulate the intestinal state of infant pneumonia.Liquid chromatography-mass spectrometry technology(LC-MS/MS)was used to detect metabolites in each group.Supervised orthogonal partial least squares discriminant analysis(OPLS-DA)model values were used for the detection results to find the differential metabolites.The metabolic pathways that are involved with the differential metabolites were clarified through enrichment analysis and topological analysis.Finally,the T cell receptor signaling pathway(TCR)signal conversion was analyzed by the network pharmacology method.Results:In the high-calorie diet combined with pneumonia group(M3),a total of 55 metabolites were determined to be different from the normal group(N).A total of 36 metabolites were determined to be different from those in the lung metabolites of the YD treatment group(T1).YD had a regulatory effect on glutathione metabolism,arginine and proline metabolism,ascorbic acid and aldehyde metabolism and phenylalanine metabolism.And the small molecule metabolites could act on the FYN and lymphocytespecific protein tyrosine kinase(LCK)target proteins in the TCR signaling pathway,thereby affecting the immune function of the lungs.Conclusion:A high-calorie diet can cause abnormal sphingolipid metabolism in the lungs of young rats,thereby creating chronic lung inflammation in young rats.YD has a beneficial effect when used to treat young rats with LPS-induced pneumonia fed on high-calorie diets.Its mechanisms of action may affect the body’s immune pathways by regulating the oxidative stress pathway affected by glutathione metabolism.
