Effects of Leonurine on Aortic Endothelial Cell Injury in Rats with Coronary Heart Disease by Regulating the RhoA/ROCK Signaling Pathway
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:Seven-ty-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),endo-thelin-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 cy-tometry was used to detect apoptosis of aortic endothelial cells.Western blot analysis was used to detect the ex-pression 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 arrange-ment,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 endo-thelium;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 signif-icant increases in LVEF,FS,HDL-C,and NO levels(P＜0.05).The Leo-H+LPA group reversed the pro-tective 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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