| 孟星星 苏玉婷 程耀萍 张海军 谢小萍 常耀明 暴军香△.丹皮酚通过酸性鞘磷脂酶/ 神经酰胺通路改善血管紧张素II 所致动脉内
皮功能障碍[J].,2016,16(21):4014-4018 |
| 丹皮酚通过酸性鞘磷脂酶/ 神经酰胺通路改善血管紧张素II 所致动脉内
皮功能障碍 |
| Paeonol Ameliorates Angiotensin II induced Endothelial Dysfunction throughAcid Sphingomyelinase/Ceramide Pathway |
| |
| DOI： |
| 中文关键词: 丹皮酚 血管紧张素II 动脉 内皮 酸性鞘磷脂酶 神经酰胺 |
| 英文关键词: Paeonol Angiotensin II Artery Endothelia Acid sphingomyelinase Ceramide |
| 基金项目:国家自然科学基金项目(81171871, 31071045, 81401550) |
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| 中文摘要: |
| 目的：探讨丹皮酚(Paeonol，Pae)对血管紧张素II(Angiotensin II，Ang II)所致动脉内皮功能障碍的保护作用及其机制。方法：
采用实时定量聚合酶链式反应(RT-PCR)和Western blot 检测酸性鞘磷脂酶(acid sphingomyelinase，ASM)基因及蛋白表达；采用免
疫组织荧光检测血管环神经酰胺(ceramide，Cer)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
啶荧光探针(dihydroethidium，DHE)检测血管环超氧阴离子(superoxide anion，O2
- ·)
水
平
。
结
果
：
与
对
照
组
相
比
，
Ang II孵
育
后
主
动
脉
对乙酰胆碱(acetylcholine，Ach) 的舒张反应显著降低，Pae 与Ang II共孵育则无明显改变；Ang II 及Pae 孵育后，动脉对硝普钠
(sodiumnitroprusside，SNP)的舒张反应均无明显变化；Ang II孵育可增高动脉环O2
-·水平，这一反应被Pae 明显抑制；与对照组相
比，Ang II孵育动脉ASMmRNA 水平无明显改变，但蛋白表达显著增加，Cer含量显著增多，Pae与Ang II共孵育动脉ASM蛋白及
Cer水平与对照组相比均无明显改变；采用神经酰胺酶抑制剂N-oleoylethanolamine (OEA)增加动脉Cer含量后，Pae 降低动脉O2
-·
水平以及增强Ach舒张反应的效应被显著抑制。结论：Pae通过ASM/Cer通路改善AngII所致动脉氧化应激增强和内皮功能障碍。 |
| 英文摘要: |
| Objective:Angiotensin II (Ang II) is a crucial mediator inducing dysfunction of endothelial cell contributing to the development
of hypertension and atherosclerosis. Paeonol (Pae) owns the ability to enhance activity of endothelial nitric oxide synthase and
lessen oxidative stress in multiple cells. Acid sphingomyelinase (ASM)/ceramide (Cer) regulates the activity of NADPH oxidase and mitochondrial
function influencing the level of reactive oxygen species upon a host pathological stimulus. We sought to investigate the protective
effect of Pae on Ang II induced arterial endothelial dysfunction and elucidate the role of ASM/Cer pathway in the situation.Methods:Reverse transcriptase polymerase chain reaction(RT-PCR) and Western blot were used to detect the gene and protein abundance of ASM.
Immunohistochemical fluorescence technique was carried out to show the content of Cer. Isometric force recording system was done to
detect the vasodilatation response. Dihydroethidiumfluorescent probes (DHE) was applied to investigate the superoxide anion (O2
- ·)
level
of vascular rings.Results:As compared to control level, the vasodilation of aorta to acetylcholine (Ach) was decreased significantly by
Ang II (100 nmol/L) (P<0.05) which could be reversed by Pae. The vasodilation to sodiumnitroprusside (SNP) did not change with treatment
of either Ang II or Pae. The O2
- ·
level of aorta ring was increased after Ang II incubation which could also be reverted by Pae. The
mRNA abundance of ASMwas not changed by Ang II whereas the protein level of it was upregulated significantly (P<0.05). At the same
time, the Cer content was increased by Ang II too (P<0.05). Similarly, the change of both the ASMprotein expression and Cer content
were prevented by Pae treatment. N-oleoylethanolamine (OEA), an acid ceramidase inhibitor was used to increase the Cer level of aorta
which was found blocking the effect of Pae reducing O2
-·level and promoting vasodilation response of aorta to Ach.Conclusion:Paeonol
ameliorates angiotensin II elicited oxidative stress and endothelial dysfunction through ASM/ Cer pathway. |
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