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|本期目录/Table of Contents|

血管紧张素II经酸性鞘磷脂酶/神经酰胺通路致动脉内皮功能障碍的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2017年第1期
页码:
34-039
栏目:
基础研究
出版日期:
2016-10-05

文章信息/Info

Title:
Acid sphingomyelinase/ceramide mediates arterial angiotensin II-induced endothelial dysfunction
作者:
苏玉婷; 孟星星; 程耀萍; 谢小萍; 张海军; 常耀明; 暴军香
（第四军医大学航空航天卫生学教研室，陕西 西安 710032）
Author(s):
SU Yu-ting;  MENG Xing-xing;  CHENG Yao-ping;  XIE Xiao-ping;  ZHANG Hai-jun;  CHANG Yao-ming;  BAO Jun-xiang
(Department of Aerospace Hygiene, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
血管紧张素II; 动脉; 内皮; 酸性鞘磷脂酶; 神经酰胺
Keywords:
angiotensin II;  artery;  endothelium;  sphingomyelinase;  ceramide
分类号:
R318.01
DOI:
-
文献标识码:
A
摘要:
目的 探讨酸性鞘磷脂酶（acid sphingomyelinase,ASM）/神经酰胺（ceramide,Cer）通路在血管紧张素II（angiotensin II,AngII）致动脉内皮功能障碍中的作用和机制。方法 针对对照组，低、中、高剂量AngⅡ组及ASM抑制剂地昔帕明（desipramine,Dpm）组，采用Western blot检测法、实时定量PCR和免疫荧光化学方法检测ASM、Cer、总内皮型一氧化氮合酶（total endothelial nitric oxide synthase,t-eNOS）和磷酸化eNOS（phosphorylated eNOS,p-eNOS）含量变化；采用血管环张力描记技术检测主动脉血管环的舒张功能；采用二氢乙啶（dihydroethidium,DHE）荧光探针检测血管环超氧阴离子（superoxide anion,O-2·）水平。结果 与对照组相比，AngⅡ孵育后主动脉对乙酰胆碱（acetylcholine,Ach）的舒张反应显著降低（P<0.05），呈剂量依赖性，对硝普钠（sodium nitroprusside,SNP）的舒张反应无明显改变；AngⅡ孵育组动脉ASM表达显著增加（P<0.05），Cer含量显著增多（P<0.05）；ASM抑制剂Dpm可显著抑制AngⅡ所致ASM和Cer改变（P<0.05），亦可使动脉对Ach的舒张反应恢复正常；AngⅡ可显著降低 动脉p-eNOS含量（P<0.05），增加O-2·水平（P<0.05），Dpm则可使p-eNOS增加 （P<0.05），降低O-2·（P<0.05）。结论 ASM/Cer可能通过抑制eNOS磷酸化并增加O-2·含量介导AngⅡI所致动脉内皮功能障碍。
Abstract:
AIM To investigate the effect and mechanism of acid sphingomyelinase (ASM)/ceramide (Cer) pathway in arterial endothelial dysfunction caused by angiotensin II (AngII). METHODSWestern blot, real-time polymerase chain reaction (RT-PCR) and immunohistochemistry were carried out to examine the content of ASM, Cer, total endothelial nitric oxide synthase (t-eNOS) and phosphorylated eNOS (p-eNOS). Isometric force recording system was used to detect vascular function. Dihydroethidium (DHE) fluorescent probe was used to evaluate the level of superoxide anion (O-2·) in arteries. RESULTSAfter incubation with AngII (100 nmol/L), the vasodilation response of aorta to acetylcholine (Ach) decreased significantly (P<0.05), which was dose dependent, whereas vasodilation response to sodium nitroprusside (SNP) did not change. ASM protein and Cer level were increased significantly by AngII incubation compared with the control level (P<0.05), which could be reduced by incubation with desipramine (Dpm), a specific ASM inhibitor. Dpm pretreatment significantly increased the vasodilation response to Ach. AngII could significantly reduce p-eNOS content of artery as well as increase the level of O-2·, whereas Dpm could increase p-eNOS and lower the level of O-2·. CONCLUSIONAngII induces endothelial dysfunction through ASM/Cer, which might inhibit the phosphorylation of eNOS and enhance the content of O-2·.

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备注/Memo

备注/Memo:
收稿日期：2016-02-20.基金项目：国家自然科学基金项目资助（31071045；81401550）
通讯作者：暴军香，副教授，主要从事失重与心血管生理学研 究Email:baojunx@fmmu.edu.cn
作者简介：苏玉婷，硕士生 Email:1538148701@qq.com
更新日期/Last Update: 2016-10-09