RÉSUMÉ
Objective To investigate the effect of vitamin B6(VB6)on vascular endothelial injury of atherosclerosis(AS)mice and its mechanism.Methods Thirty-six ApoE-/-mice were randomly divided into control group,AS group,VB6 group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group,with 6 mice in each group.The mice in the AS group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group were fed with high-fat diet for 12 weeks to establish the AS model;the mice in the control group and VB6 group were given regular diet and normal drinking water for 12 weeks.After 12 weeks,the mice in the control group were given conventional diet and the same volume of physiological saline as the VB6 group daily by gavage;the mice in the VB6 group were given routine diet and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+LiCl group were given high-fat diet continuously and LiCl(1 mg·kg-1)by gavage daily;the mice in the AS+VB6 group were given high-fat diet continuously and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+VB6+LiCl group were given high-fat diet continuously and VB6(50 mg·kg-1),LiCl(1 mg·kg-1)by gavage daily;all mice were intervened for 4 weeks.After intervention,the serum nitric oxide(NO),malondialdehyde(MD A)levels and superoxide dismutase(SOD)activity of mice in each group were measured by enzyme linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the morphology of thoracic aortic tissue of mice in each group and the percentage of AS plaque area to total vascular area was calculated.The vasodilatation rate of thoracic aorta was detected by isolated vascular ring experiment.The expression of sodium/hydrogen exchanger 1(NHE1)protein in thoracic aorta was detected by immunohistochemistry.Results Compared with the control group,the NO level and SOD activity in the serum of mice in the AS group decreased,while the MDA level increased(P＜0.05);there was no significant difference in the NO,MDA levels and SOD activity in the serum of mice between the VB6 group and the control group(P＞0.05).Compared with the AS group,the serum NO level and SOD activity of mice in the AS+VB6 group increased,while the MDA level decreased(P＜0.05);there was no significant difference in serum NO,MDA levels and SOD activity of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).Compared with the AS+VB6 group,the serum NO level and SOD activity of mice in the AS+VB6+LiCl group decreased,while the MDA level increased(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice among the VB6 group and the control group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).In the control group,the vascular endothelium of mice was smooth with orderly arrangement of cells;in the AS group,AS+LiCl group and AS+VB6+LiCl group,the tissue structure of vascular of mice was disordered and the vascular endothelium was rough;in the VB6 group and AS+VB6 group,the vascular wall structure of mice was normal,the vascular endothelium was smooth,and the cells were arranged orderly.The vasodilatation rate of thoracic aorta of mice induced by acetylcholine(Ach)in the AS group was significantly lower than that in the control group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between the VB6 group and the control group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).There was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by sodium nitroprusside among the six groups(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice between the VB6 group and the control group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice among the AS+LiCl group,AS+VB6+LiCl group and the AS group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).Conclusion VB6 can improve vascular endothelial injury in AS mice via inhibiting the expression of NHE1 protein.