[1]朱茉莉,李怡霏,李珍珍,等.维生素B6对动脉粥样硬化小鼠血管内皮损伤的影响及作用机制[J].新乡医学院学报,2024,(1):001-7.[doi:10.7683/xxyxyxb.2024.01.001]
　ZHU Moli,LI Yifei,LI Zhenzhen,et al.Effect of vitamin B6 on vascular endothelial injury of atherosclerosis mice and its mechanism[J].Journal of Xinxiang Medical University,2024,(1):001-7.[doi:10.7683/xxyxyxb.2024.01.001]
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维生素B6对动脉粥样硬化小鼠血管内皮损伤的影响及作用机制
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
期数:
2024年1
页码:
001-7
栏目:
基础研究
出版日期:
2024-01-05

文章信息/Info

Title:
Effect of vitamin B6 on vascular endothelial injury of atherosclerosis mice and its mechanism
作者:
朱茉莉; 李怡霏; 李珍珍; 赵海燕; 刘艳华; 邱月; 万光瑞; 李鹏
（新乡医学院药学院,河南　新乡　453003）
Author(s):
ZHU Moli; LI Yifei; LI Zhenzhen; ZHAO Haiyan; LIU Yanhua; QIU Yue; WAN Guangrui; LI Peng
(School of Pharmacy,Xinxiang Medical University,Xinxiang 453003,Henan Province,China)
关键词:
维生素B6; 钠氢交换蛋白1; 内皮损伤; 动脉粥样硬化; 氧化应激
Keywords:
vitamin B6; sodium/hydrogen exchanger 1; endothelial injury; atherosclerosis; oxidative stress
分类号:
R543.5
DOI:
10.7683/xxyxyxb.2024.01.001
文献标志码:
A
摘要:
目的　探讨维生素B6（VB6）对动脉粥样硬化(AS）小鼠血管内皮损伤的影响及作用机制。
方法　将36只ApoE-/-小鼠随机分为对照组、AS组、VB6组、AS+LiCl组、AS+VB6组和AS+VB6+LiCl组，每组6只。AS组、AS+LiCl组、AS+VB6组和AS+VB6+LiCl组小鼠高脂饮食12周建立AS模型；对照组和VB6组小鼠常规饮食、正常饮水12周。12周后，对照组小鼠常规饮食，每日给予和VB6组等体积的生理盐水灌胃；VB6组小鼠常规饮食，每日灌胃给予VB6（50 mg·kg-1）；AS+LiCl组小鼠继续给予高脂饮食，每日灌胃给予LiCl（1 mg·kg-1）；AS+VB6组小鼠继续给予高脂饮食，每日灌胃给予VB6（50 mg·kg-1）；AS+VB6+LiCl组小鼠继续给予高脂饮食，每日灌胃给予VB6（50 mg·kg-1）和LiCl（1 mg·kg-1）；6组小鼠均干预4周。干预结束后，采用酶联免疫吸附试验检测各组小鼠血清中一氧化氮(NO)、丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性。苏木精-伊红染色观察各组小鼠胸主动脉组织形态，并计算AS斑块面积占血管总面积的百分比。离体血管环实验检测胸主动脉舒张率。免疫组织化学法检测胸主动脉中钠氢交换蛋白1（NHE1）表达。
结果　与对照组相比，AS组小鼠血清中NO水平和SOD活性显著下降，MDA水平显著升高（P<0.05）；VB6组与对照组小鼠血清中NO、MDA水平和SOD活性比较差异无统计学意义（P>0.05）。与AS组相比，AS+VB6组小鼠血清中NO水平和SOD活性显著上升，MDA水平显著下降（P<0.05）；AS+LiCl组、AS+VB6+LiCl组与AS组小鼠血清中NO、MDA水平和SOD活性比较差异无统计学意义（P>0.05）。与AS+VB6组相比， AS+VB6+LiCl组小鼠血清中NO水平和SOD活性显著下降，MDA水平显著升高（P<0.05）。AS组小鼠AS斑块面积占血管总面积的百分比显著高于对照组（P<0.05）；VB6组与对照组小鼠AS斑块面积占血管总面积的百分比比较差异无统计学意义（P<0.05）。AS+VB6组小鼠斑块面积占血管总面积的百分比显著低于AS组（P<0.05）；AS+LiCl组、AS+VB6+LiCl组与AS组小鼠AS斑块面积占血管总面积的百分比比较差异无统计学意义（P<0.05）。AS+VB6+LiCl组小鼠AS斑块面积占血管总面积的百分比显著高于AS+VB6组（P<0.05）。对照组小鼠血管内皮光滑平整，细胞排列整齐有序；AS组、AS+LiCl组和AS+VB6+LiCl组小鼠的血管组织结构紊乱、血管内皮粗糙；VB6组和AS+VB6组小鼠的血管壁结构正常、血管内皮光滑、细胞排列有序。AS组小鼠乙酰胆碱（Ach）诱导的胸主动脉舒张率显著低于对照组（P<0.05）； VB6组与对照组小鼠Ach诱导的胸主动脉舒张率比较差异无统计学意义（P>0.05）。AS+VB6组小鼠Ach诱导的胸主动脉舒张率显著低于AS组（P<0.05）；AS+LiCl组、AS+VB6+LiCl组与AS组小鼠Ach诱导的胸主动脉舒张率比较差异无统计学意义（P>0.05）。AS+VB6+LiCl组小鼠Ach诱导的胸主动脉舒张率显著高于AS+VB6组（P<0.05）。6组小鼠硝普钠诱导的胸主动脉舒张率比较差异均无统计学意义（P>0.05）。AS组小鼠胸主动脉中NHE1蛋白表达量百分比显著高于对照组（P<0.05）；VB6组与对照组小鼠胸主动脉中NHE1蛋白表达量百分比比较差异无统计学意义（P>0.05）。AS+VB6组小鼠胸主动脉中NHE1蛋白表达量百分比显著低于AS组（P<0.05）；AS+LiCl组、AS+VB6+LiCl组与AS组小鼠胸主动脉中NHE1蛋白表达量百分比比较差异无统计学意义（P>0.05）。AS+VB6+LiCl组小鼠胸主动脉中NHE1蛋白表达量百分比显著高于AS+VB6组（P<0.05）。
结论　VB6可通过抑制NHE1蛋白的表达来改善AS小鼠的血管内皮损伤。
Abstract:
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(MDA) 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.

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更新日期/Last Update: 2024-01-05