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
Objective To 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.Methods Twenty-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 pro-tein(CRP)levels;UPLC MS/MS technology was used for widely targeted metabolomics detection in serum,and mul-tivariate 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.Results Compared 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 inti-mal 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 path-ways.The two medications jointly regulated 38 metabolites.Glycerophospholipid metabolism and arginine-related me-tabolism 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 meta-bolic 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.Com-pared 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 atorvas-tatin 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).Conclusions Both 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.
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