Objective To investigate the role and mechanism of low concentration of cadmium in promoting atherosclerosis in kdrl:EGFP transgenic zebrafish.Methods Eighteen healthy adult zebrafish with endothelial cell-specific expression of enhanced green fluorescent protein[Tg(kdrl:EGFP)]were selected to establish zebrafish models of atherosclerosis.According to different treatment methods,they were divided into group A(blank control group),group B(30 μmol/L of cadmium)and group C(30 μmol/L of cadmium + atorvastatin),with six zebrafish in each group.Surgical removal of blood vessels and plaque tissues from each group of zebrafish was performed.The accumulation of cholesterol in the blood vessels of each group of zebrafish was observed using a fluorescence microscope,and the thickness of the vascular endothelium was measured.Hematoxylin-eosin(HE)staining was used to detect the pathological changes of plaques in the blood vessels of each group of zebrafish.The quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were applied to detect the mRNA and protein expression levels of HIF-1α,p-Akt,p-P70 and VEGF in the plaques in the blood vessels of each group,respectively.Results Compared with the group A,the serum concentration of cadmium was higher in the group B and the group C(P<0.05).Compared with the group A and the group C,the thickness of the vascular endothelium was significantly increased and there was a significant accumulation of cholesterol in the blood vessels of zebrafish(P<0.05).The HE staining revealed that the group B exhibited more significant infiltration of inflammatory cells and steatosis,with the cell nucleus suspended in the center or squeezed to the side compared with the group A and the group C.The relative mRNA and protein expressions of HIF-1α,p-Akt,p-P70 and VEGF in plaques in the blood vessels of the group B were higher than those in the group A and the group C(P<0.05).Conclusions Low concentrations of cadmium facilitates atherosclerosis in kdrl:EGFP transgenic zebrafish,and the underlying mechanisms are related to HIF-1α,p-Akt,p-P70 and VEGF.Atorvastatin could reverse the atherosclerosis promoted by the cadmium.
关键词
血管粥样硬化/低浓度镉/kdrl:EGFP转基因/缺氧诱导因子-1a/阿托伐他汀
Key words
atherosclerosis/low concentration of cadmium/kdrl:EGFP transgenic/hypoxia-inducible factor 1-alpha/atorvastatin
维普
万方数据