Objective To investigate the effect of verbascoside(VB)on endothelial dysfunction in atherosclerotic(AS)rats by regulating high-mobility group protein B1(HMGB1)/receptor for advanced glycation endproducts(RAGE)/nuclear factor κB(NF-κB)signal pathway.Methods The rat model of AS was established by high fat feeding combined with vitamin D3 solution intraperitoneal injection.Rats were divided into the control group(n=10),the model group(n=12),the low(VB-L),medium(VB-M)and high dose(VB-H)VB groups(2,5 and 10 mg/kg,n=10),and the positive control group(simvastatin,5 mg/kg,n=10).The serum level of blood lipids was detected by automatic biochemical analyzer.Pathological changes of aorta were observed by HE staining.Serum levels of inflammatory factors and vascular endothelial cytokines were detected by enzyme-linked immunosorbent assay(ELISA).The level of oxidative stress in rats was detected by micro-method kit.The expression of HMGB1/RAGE signal pathway protein in aorta was detected by Western blot assay.Results Compared with the control group,the intima of aorta in the model group was thickened,plaque appeared in blood vessels,accompanied by lipid deposition and inflammatory cell infiltration.Serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),C-reactive protein(CRP),matrix metalloproteinase-9(MMP-9),endothelin-1(ET-1),visfatin,intercellular adhesion molecule-1(ICAM-1)and malondialdehyde(MDA),and HMGB1,RAGE and phosphorylation levels of NF-κB in aorta were obviously increased.Serum levels of high-density lipoprotein cholesterol(HDL-C),nitric oxide(NO),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were obviously decreased(P＜0.05).Compared with the model group,pathological changes of rats were obviously improved in the VB-L,VB-M and VB-H groups and the simvastatin group.Serum levels of TC,TG,LDL-C,TNF-α,IL-1β,CRP,MMP-9,ET-1,visfatin,ICAM-1,MDA,and HMGB1,RAGE,phosphorylation levels of NF-κB in aorta were obviously decreased,and serum levels of HDL-C,NO,SOD and GSH-Px were obviously increased(P＜0.05).Conclusion VB can down-regulate the expression of HMGB1/RAGE/NF-κB signal pathway protein,inhibit inflammation and oxidative stress in AS rats,and improve lipid metabolism and vascular endothelial function.

Acute myocardial infarction with cardiogenic shock (AMI-CS) refers to the rapid decrease in cardiac output in a short period of time, and it leads to severe insufficient perfusion of various organs and causes systemic microcirculatory dysfunction, which is the most common cause of the death of patients with acute myocardial infarction (AMI). At present, the main strategy for clinical treatment of AMI-CS is revascularization, which reduces the mortality of AMI-CS. However, myocardial ischemia and reperfusion can cause ischemia/reperfusion (I/R) injury, induce myocardial mitochondrial dysfunction, and a large amount of reactive oxygen species (ROS) accumulation. Mitochondrial-mediated apoptosis of cardiomyocytes is the main reason of cardiomyocyte death during reperfusion injury. This article summarizes the role of mitochondrial in AMI-CS, which focus on three aspects of mitochondrial permeability transition pore (mPTP) opening, mitochondrial autophagy and mitochondrial fusion/division. It is expected to provide new ideas for clinical AMI-CS and identify potential complications targets.