Effect of Picroside Ⅱ on endothelial cell damage in rats with coronary heart disease by regulating HMGB1/RAGE signaling pathway
Objective:To investigate effect of Picroside Ⅱ(P-Ⅱ)on endothelial cell damage in rats with coronary heart disease(CHD)by regulating high mobility group box 1 protein(HMGB1)/receptor for advanced glycation end products(RAGE)signaling pathway.Methods:SPF grade SD rats were randomly separated into control group,CHD group,P-Ⅱ low,medium,high doses groups and P-Ⅱ high dose+DEX group(P-Ⅱ high dose+HMGB1/RAGE signaling pathway activator DEX).Except for control group,CHD rat model was established by high-fat diet combined with intraperitoneal injection of pituitrin,corresponding drugs were administered by gavage or intraperitoneal injection,once a day for 4 consecutive weeks.Biochemical analyzer was applied to measure blood lipid levels;ELISA was applied to detect levels of serum nitric oxide(NO),endothelin(ET)-1,angiotensin Ⅱ(AngⅡ),TNF-α,IL-1β and IL-6;kits were applied to detect levels of reactive oxygen species(ROS)and glutathione peroxidase(GSH-Px)in coronary artery tissue;HE staining was applied to observe pathological damage in coronary artery tissue;TUNEL staining was applied to observe apoptosis of vascular endothelial cells;Western blot was applied to detect expressions of vascular endothelial growth factor(VEGF),HMGB1 and RAGE proteins in coronary artery tissue.Results:Compared with control group,levels of TC,TG,LDL-C,ET-1,AngⅡ,TNF-α,IL-1β,IL-6,ROS,endothelial cell apoptosis rate,and expressions of HMGB1 and RAGE in rats in CHD group were signifi-cantly increased,levels of HDL-C,NO,GSH-Px,and expression of VEGF were significantly reduced(P<0.05);compared with CHD group,levels of TC,TG,LDL-C,ET-1,AngⅡ,TNF-α,IL-1β,IL-6,ROS,endothelial cell apoptosis rate,and expressions of HMGB1 and RAGE in P-Ⅱ low,medium and high doses groups were obviously reduced,levels of HDL-C,NO,GSH-Px,and expression of VEGF were obviously increased(P<0.05);HMGB1/RAGE signaling pathway activator DEX was able to attenuate protective effect of P-Ⅱ on endothelial cell damage in CHD rats.Conclusion:P-Ⅱ can effectively alleviate endothelial cell damage in CHD rats,whose mechanism may be related to inhibition of HMGB1/RAGE pathway activation.
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