Abstract：Objective: To investigate the effect and mechanism of leonurine (Leo) on aortic endothelial cell injury in rats with coronary heart disease (CHD) by regulating the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase (ROCK) signaling pathway.Methods: Seventy-five successfully modeled CHD rats were randomly divided into five groups: model group (CHD group), low, medium, and high dose Leo groups (Leo-L, Leo-M, Leo-H groups), and Leo-H dose group combined with RhoA activator LPA group (Leo-H+LPA group), with 15 rats in each group. The Leo-L, Leo-M, and Leo-H groups were gavaged with 15, 30, and 60mg·kg-1·d-1 of Leo, respectively. The Leo-H+LPA group was gavaged with 60mg·kg-1·d-1 of Leo and intraperitoneally injected with 1mg·kg-1·d-1 of LPA. The Control and CHD groups were administered equal volumes of normal saline in the same manner for four weeks. Cardiac function indicators were measured by echocardiography. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured using an automatic biochemical analyzer. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), endothelin-1 (ET-1), endothelial cell-specific molecule-1 (EMS1), and vascular cell adhesion molecule-1 (VCAM-1). Hematoxylin and eosin (HE) staining was used to observe aortic endothelial damage. Flow cytometry was used to detect apoptosis of aortic endothelial cells. Western blot analysis was used to detect the expression of proteins related to the RhoA/ROCK signaling pathway.Results: Compared with the Control group, the CHD group showed significant aortic wall thickening, uneven staining, cell swelling, disordered arrangement, and rough endothelium; significant increases in left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), TC, TG, LDL-C, IL-6, TNF-α, ET-1, VCAM-1, EMS1 levels, cell apoptosis rate, and RhoA, ROCK1, and ROCK2 protein expression (P<0.05); and significant decreases in left ventricular ejection fraction (LVEF), fractional shortening (FS), HDL-C, and NO levels (P<0.05). Compared with the CHD group, the Leo-L, Leo-M, and Leo-H groups showed uniform aortic staining, clear arterial wall structure, tightly arranged and morphologically normal cells, and smoother endothelium; significant decreases in LVEDD, LVESD, TC, TG, LDL-C, IL-6, TNF-α, ET-1, VCAM-1, EMS1 levels, cell apoptosis rate, and RhoA, ROCK1, and ROCK2 protein expression (P<0.05); and significant increases in LVEF, FS, HDL-C, and NO levels (P<0.05). The Leo-H+LPA group reversed the protective effects of Leo on CHD rats (P<0.05).Conclusion: Leonurine may improve cardiac function, reduce blood lipids, and inhibit inflammation in CHD rats by inhibiting the RhoA/ROCK signaling pathway, thereby alleviating aortic endothelial cell injury.
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2024, Vol. 30 
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