1.Comparative Study on Effect of Yiqi Liangxue Shengji Formula (益气凉血生肌方) and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats
Tianshi MAO ; Long XIE ; Qun GAO ; Yi PAN ; Wenhao JIA ; Qian LIN
Journal of Traditional Chinese Medicine 2024;65(11):1180-1188
ObjectiveTo compare the effects and differences of Yiqi Liangxue Shengji Formula (益气凉血生肌方) and atorvastatin on the repair of vascular injury in rats from the perspective of metabolomics. MethodsTwenty-four male SD rats were randomly divided into sham-surgery, model, traditional Chinese medicine (TCM), and ator-vastatin groups, with 6 rats in each group. The rat model was established by balloon-induced abdominal aorta injury. Gavage was started on the day after surgery in all groups of rats. The sham and model groups were given with deio-nized water, TCM group received Yiqi Liangxue Shengji Formula 6 g/(kg·d), and the atorvastatin group treated with atorvastatin suspension 2 mg/(kg·d) for 4 weeks. HE staining was used to observe the pathological morphology of the injured segment of the abdominal aorta; ELISA detection was used to test serum nitric oxide (NO) and C-reactive protein (CRP) levels; UPLC MS/MS technology was used for widely targeted metabolomics detection in serum, and multivariate statistical analysis was used to screen metabolic markers and pathways of two drugs; finally, compare serum levels of key metabolic markers of the above two medications in rats of each group. ResultsCompared with the sham-surgery group, the neointima significantly thickened, the level of NO decreased significantly and the level of CRP increased in serum of the model group (P<0.01); compared with the model group, the degree of arterial intimal hyperplasia in TCM group and atorvastatin group reduced, with an increase in NO levels and a decrease in CRP levels (P< 0.05 or P<0.01). The results of serum metabolomics showed that TCM group obtained 49 metabolic markers and 6 metabolic pathways, while atorvastatin group obtained 41 metabolic markers and 4 metabolic pathways. The two medications jointly regulated 38 metabolites. Glycerophospholipid metabolism and arginine-related metabolism were common metabolic pathways for both medications. Lysophosphatidylcholine (16∶1/0∶0) [LPC (16∶1/ 0∶0)], phosphatidylcholine (15∶0/15∶0) [PC (15∶0/15∶0)] were the key metabolites of glycerophospholipid metabolic pathway; ornithine, spermidine were the key metabolites of arginine-related metabolic pathway. The tricarboxylic acid cycle and glutathione metabolism were the unique metabolic pathways of Yiqi Liangxue Shengji Formula. Compared with the sham-surgery group, LPC (16∶1/0∶0), ornithine, and spermidine levels elevated and PC (15∶0/15∶0) levels decreased in the model group (P<0.05 or P<0.01). Compared with the model group, LPC (16∶1/0∶0), ornithine, and spermidine levels decreased, and PC (15∶0/15∶0) levels increased in both TCM group and atorvastatin group (P<0.05 or P<0.01). The degree of LPC reduction (16∶1/0∶0) was more significant in atorvastatin group compared with that in the TCM group (P<0.01). ConclusionsBoth sham-surgery and atorvastatin could regulate lipid metabolism and arginine-related metabolism, exert the characteristics of lipid-lowering, anti-inflammatory, improve arginine/NO bioavailability, and improve endothelial dysfunction. Atorvastatin showed more advantages in lipid-lowering and anti-inflammatory, while Yiqi Liangxue Shengji Formula has unique characteristics in regulating energy metabolism and improving oxidative stress.