[1]高飞,胡晓露,陈康宁.PPAR-γ激动剂抑制血管紧张素Ⅱ诱导血管平滑肌细胞的表型转化[J].第三军医大学学报,2017,39(03):229-235.
 Gao Fei,Hu Xiaolu,Chen Kangning.Peroxisome proliferators-activated receptor-gamma agonist inhibits angiotensin Ⅱ-induced phenotypic switching of vascular smooth muscle cells[J].J Third Mil Med Univ,2017,39(03):229-235.
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PPAR-γ激动剂抑制血管紧张素Ⅱ诱导血管平滑肌细胞的表型转化(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
39卷
期数:
2017年第03期
页码:
229-235
栏目:
基础医学
出版日期:
2017-02-15

文章信息/Info

Title:
Peroxisome proliferators-activated receptor-gamma agonist inhibits angiotensin Ⅱ-induced phenotypic switching of vascular smooth muscle cells
作者:
高飞胡晓露陈康宁
第三军医大学西南医院神经内科
Author(s):
Gao Fei Hu Xiaolu Chen Kangning

Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

关键词:
过氧化物酶体增殖物激活受体-&gammaAngⅡ平滑肌细胞
Keywords:
分类号:
R322.12; R329.24; R977.12
文献标志码:
A
摘要:

目的      探讨过氧化物酶体增殖物激活受体(peroxisome proliferator activated receptor gamma,PPAR-γ)激动剂罗格列酮(rosiglitazone,RSG)对血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)诱导小鼠血管平滑肌细胞(vascular smooth muscle cells,VSMCs)表型转化的抑制作用及其可能的机制。方法       体外培养小鼠血管平滑肌细胞,应用AngⅡ诱导VSMCs的表型转化,给予罗格列酮预处理后用Transwell检测细胞迁移并在激光共聚焦显微镜下观察细胞微丝骨架,用RT=qPCR和Western blot分别检测PPAR=γ、PKGⅠα以及VSMCs收缩型标志因子(smooth muscle 22  alpha,SM22α)mRNA和蛋白水平。应用PPAR=γ抑制剂预处理后再给予罗格列酮刺激,Western blot检测PKGⅠα和SM22α蛋白水平。结果       ①罗格列酮(20 μmol/L)预处理可抑制AngⅡ诱导VSMCs的迁移(P<0.05)。     ②罗格列酮(20 μmol/L)预处理后可抑制AngⅡ诱导VSMCs微丝骨架的形成。      ③RT-qPCR检测结果显示:罗格列酮(20 μmol/L)预处理后可抑制AngⅡ诱导PKGⅠα和SM22α mRNA的下调作用(P<0.05)。      ④Western blot检测结果显示:罗格列酮(20 μmol/L)预处理后可抑制AngⅡ诱导PKGⅠα和SM22α蛋白水平的下调作用(P<0.05);PPAR-γ抑制剂GW9662可减弱罗格列酮对PKGⅠα和SM22α的促表达作用(P<0.05)。结论      罗格列酮通过激活PPAR-γ来抑制AngⅡ诱导VSMCs的表型转化,激活PPAR-γ可能通上调PKGⅠα表达发挥上述作用。

Abstract:

Objective      To investigate the inhibitory effect of peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, rosiglitazone (RSG), on the phenotypic switching in vascular smooth muscle cells (VSMCs) induced by angiotensin Ⅱ (AngⅡ). Methods            AngⅡ was employed to induce phenotypic switching in cultured mouse VSMCs. After pretreated with RSG and then treated with AngⅡ, the migration of VSMCs was analyzed by Transwell chamber assay, and F-actin polymerization was detected by Phalloidine-iFluorTM 488 staining under a laser confocal microscope. The protein and mRNA levels of PPAR-γ, PKGⅠα and smooth muscle 22 -alpha (SM22α, a marker molecule in differentiated VSMC with contractile phenotype) were measured by Western blotting and RT-qPCR. Also, Western blotting was employed to detect protein levels of PKGⅠα and SM22α in the VSMCs which were pretreated with PPAR-γ inhibitor, GW9662 before RSG stimulation. Results      RSG (20 μmol/L) pretreatment significantly inhibited AngⅡ-induced VSMCs immigration (P<0.05) and formation of actin cytoskeleton. Results from RT-qPCR indicated that RSG pretreatment also reversed the down-regulation of PKGⅠα and SM22α at mRNA and protein levels in Ang Ⅱ-stimulated VSMCs (all P<0.05). However, GW9662 treatment could attenuate the up-regulation of PKGⅠα and SM22α in RSGtreated VSMCs (P<0.05). Conclusion      RSG inhibits the phenotypic switching of VSMCs from a “contractile” to a “synthetic” state in response to Ang Ⅱ through activating PPAR-γ, and then up-regulating PKGⅠα.

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更新日期/Last Update: 2017-02-05