Background: It has been recognized that exercise training can attenuate the progression of
atherosclerosis (AS). The combined application of components from the fruit of Crataegus pinnatifida Bge. Var. major N.E. Br. (CP) and the root of Salvia miltiorrhiza Bge. (SM) has been effective in the prevention and treatment of
atherosclerosis. The present work aims to investigate the joint effects of extracts from the fruit of CP and the root of SM with swimming on
atherosclerosis in rats. Method: To establish a rat
atherosclerosis model, a combined method of partial
ligation of the left common carotid artery leading to low shear stress and a high-fat diet was employed. Blood samples were collected to detect the blood
lipid profile, which included total
cholesterol (T-CHO),
low-density lipoprotein cholesterol (
LDL-C),
triglycerides (TG) and
high-density lipoprotein cholesterol (HDL-C); endothelial
cytokines such as 6-keto-prostaglandin F1α (PGF1α),
endothelin (ET),
thromboxane B2 (TXB2),
plasminogen activator inhibitor-1 (PAI-1), and
von Willebrand factor (vWF); and inflammatory
cytokines such as interleukin-1β (IL-1β),
interleukin-6 (IL-6) and
interleukin-10 (IL-10). Finally, the common carotid arteries of the rats were removed to observe pathological changes via
oil red O staining, and the gene expression of t-PA,
PAI-1, and vWF was assayed via real-time (RT) quantitative polymerase chain reaction (qPCR). Results: The joint effects of CPSM extract and swimming indicated significant interactions, including (1) decreased serum T-CHO, TG, and
LDL-C; (2) decreased
IL-6 and increased IL-10; (3) decreased TXB2,
PAI-1 and vWF; three-dimensional analysis showed that gene expression of
PAI-1 was inhibited, vWF gene expression was downregulated, and COX-1 gene expression was increased; and (4) decreased
lipoprotein retention in the carotid artery wall. Conclusion: This research demonstrates that the combined
therapy of CP and SM extracts with swimming can improve blood
lipid levels and endothelial functions and attenuate the early signs of
atherosclerosis in a rat model of
atherosclerosis. The regulation of the gene expression of PAI, vWF and COX-1 may be the underlying cause of the effect. Methodologically speaking, three-dimensional surface plots of the joint effects of CPSM extract and swimming on parameters with quadratic fitting yielded a more accurate equation for describing the dose-response relationship in biomechanopharmacology. Such plots are likely worth using in pharmacology to quantify the effects induced by two medicinal factors.