ABSTRACT
Objective@#To explore the mechanism of Shengxian decoction in the treatment of heart failure by using metabolomic technology.@*Methods@#Rats were randomly divided into the control group, model group and administration group according to body weight, with 10 rats in each group. Rats in model group and administration group were induced by intraperitoneal injection of adriamycin to duplicate rat heart failure model. The rats in the treatment group were given Shengxian decoction 3.83 g/kg, while those in the control group and model group were given distilled water of equal volume once a day for 4 weeks. The levels of CK, AST, LDH and MDA in serum of rats were detected by ultraviolet spectrophotometer, and the metabolite profiles were collected by high resolution tandem mass spectrometry. The data were analyzed by principal component analysis and partial least squares discriminant analysis. Metabolic pathways were obtained by pathway enrichment analysis, focusing on key metabolic enzymes and metabolic pathways.@*Results@#Compared with the model group, the serum CK (1 015.44 ± 201.49 U/L vs. 1 301.89 ± 311.54 U/L), AST (210.59 ± 80.34 U/L vs. 421.56 ± 120.32 U/L), LDH (1 211.64 ± 416.61 U/L vs. 601.58 ± 311.74 U/L) in the administration group significantly decreased (P<0.05), and MDA (209.21 ± 151.15 nmol/ml vs. 1 251.15 ± 110.64 nmol/ml) levels significantly increased (P<0.05). The metabolic distribution of rats in the control group was significantly separated from that in the model group, and the administration group was between the two groups. After dimension reduction, blood biomarkers were obtained by partial least squares discriminant analysis, including citric acid, succinic acid, malic acid, arachidonic acid, canine uric acid, serine, sphingosine, Cer (d18:0/14:0), SM (d18:1/22:0), SM [d18:0/18:1 (11Z)], SM (d18:0/16:1). Metabo Analyst 4.0 analysis showed abnormal metabolism in heart failure rats, which mainly involved arachidonic acid metabolism, glycine, serine and threonine metabolism, sphingolipid metabolism, citric acid metabolism and aminoacyl-tRNA biosynthesis.@*Conclusions@#The Shengxian decoction has a good therapeutic effect on heart failure rats. Regulation of arachidonic acid metabolism, glycine, serine and threonine metabolism, sphingolipid metabolism, citric acid metabolism and aminoacyl-tRNA biosynthesis may be the key mechanisms for its treatment of heart failure.
ABSTRACT
Objective To explore the mechanism of Shengxian decoction in the treatment of heart failure by using metabolomic technology. Methods Rats were randomly divided into the control group, model group and administration group according to body weight, with 10 rats in each group. Rats in model group and administration group were induced by intraperitoneal injection of adriamycin to duplicate rat heart failure model. The rats in the treatment group were given Shengxian decoction 3.83 g/kg, while those in the control group and model group were given distilled water of equal volume once a day for 4 weeks. The levels of CK, AST, LDH and MDA in serum of rats were detected by ultraviolet spectrophotometer, and the metabolite profiles were collected by high resolution tandem mass spectrometry. The data were analyzed by principal component analysis and partial least squares discriminant analysis. Metabolic pathways were obtained by pathway enrichment analysis, focusing on key metabolic enzymes and metabolic pathways. Results Compared with the model group, the serum CK (1 015.44 ± 201.49 U/L vs. 1 301.89 ± 311.54 U/L), AST (210.59 ± 80.34 U/L vs. 421.56 ± 120.32 U/L), LDH (1 211.64 ± 416.61 U/L vs. 601.58 ± 311.74 U/L) in the administration group significantly decreased (P<0.05), and MDA (209.21 ± 151.15 nmol/ml vs. 1 251.15 ± 110.64 nmol/ml) levels significantly increased (P<0.05). The metabolic distribution of rats in the control group was significantly separated from that in the model group, and the administration group was between the two groups. After dimension reduction, blood biomarkers were obtained by partial least squares discriminant analysis, including citric acid, succinic acid, malic acid, arachidonic acid, canine uric acid, serine, sphingosine, Cer (d18:0/14:0), SM (d18:1/22:0), SM [d18:0/18:1 (11Z)], SM (d18:0/16:1). Metabo Analyst 4.0 analysis showed abnormal metabolism in heart failure rats, which mainly involved arachidonic acid metabolism, glycine, serine and threonine metabolism, sphingolipid metabolism, citric acid metabolism and aminoacyl-tRNA biosynthesis. Conclusions The Shengxian decoction has a good therapeutic effect on heart failure rats. Regulation of arachidonic acid metabolism, glycine, serine and threonine metabolism, sphingolipid metabolism, citric acid metabolism and aminoacyl-tRNA biosynthesis may be the key mechanisms for its treatment of heart failure.