[1]汪小英,余艳荣,王美玲,等.吴茱萸次碱抑制AngⅡ诱导的血管平滑肌Cx43表达上调[J].中国药理学通报,2018,(08):1139-1145.[doi:10.3969/j.issn.1001-1978.2018.08.021]
 WANG Xiao-ying,YU Yan-rong,WANG Mei-ling,et al.Rutaecarpine prevents up-regulation of Cx43 in vascular smooth muscle cells induced by angiotensin Ⅱ[J].Chinese Pharmacological Bulletin,2018,(08):1139-1145.[doi:10.3969/j.issn.1001-1978.2018.08.021]
点击复制

吴茱萸次碱抑制AngⅡ诱导的血管平滑肌Cx43表达上调()
分享到:

《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
1139-1145
栏目:
论著
出版日期:
2018-07-26

文章信息/Info

Title:
Rutaecarpine prevents up-regulation of Cx43 in vascular smooth muscle cells induced by angiotensin Ⅱ
文章编号:
1001-1978(2018)08-1139-07
作者:
汪小英2余艳荣3王美玲1彭维杰23罗 丹1
南昌大学1.基础医学院生理学系、2.药学院药理重点实验室、3.江西省医学科学院,江西 南昌 330006
Author(s):
WANG Xiao-ying2YU Yan-rong3WANG Mei-ling1PENG Wei-jie23LUO Dan1
1.Dept of Physiology,School of Medical Sciences; 2.Key Lab of Pharmacology,School of Pharmaceutical Science; 3.Academy of Medical Sciences,Nanchang University,Nanchang 330006,China
关键词:
吴茱萸次碱 缝隙连接蛋白43 辣椒素受体 平滑肌细胞 增殖 表型转换
Keywords:
rutaecarpine Cx43 TRPV1 VSMCs proliferation phenotypic switch
分类号:
R284.1; R322.74; R329.24; R341; R392.11
DOI:
10.3969/j.issn.1001-1978.2018.08.021
文献标志码:
A
摘要:
目的 探讨吴茱萸次碱(rutaecarpine,Rut)对血管紧张素Ⅱ(AngⅡ)诱导的缝隙连接蛋白43(Cx43)表达,血管平滑肌细胞(VSMCs)增殖和表型改变的影响及可能机制。方法 加入不同浓度的Rut(0.3、1.0、3.0 μmol·L-1)预处理VSMCs 10 min后,加入AngⅡ(1 μmol·L-1)共同孵育24 h,应用辣椒素受体(transient receptor potential vanilloid 1,TRPV1)竞争性拮抗剂Capsazepine(CAPZ,10 μmol·L-1),探讨TRPV1是否介导Rut的效应。Western blot检测VSMCs中Cx43和NF-κB亚基p65的水平,免疫细胞化学判断p65核转位。CCK-8和EdU法检测VSMCs增殖,Western blot检测细胞周期蛋白Cyclin D1,确定对细胞周期的影响; Western blot检测收缩型标志蛋白α-SMA和Calponin水平。结果 Rut可抑制AngⅡ诱导的Cx43表达上调,并抑制p65核转位,预先给予CAPZ可取消此效应。Rut抑制AngⅡ诱导的VSMCs增殖,表现为抑制VSMCs的DNA合成及细胞活力,还可抑制VSMCs表型转化,以上效应均被CAPZ部分阻断。结论 Rut可下调Cx43表达,从而抑制AngⅡ诱导的VSMCs增殖和表型转换,其机制涉及TRPV1/NF-κB信号途径。
Abstract:
Aim To investigate the effect of rutae-carpine(Rut)on expression of connexin43(Cx43)and the proliferation and phenotypic switch of vascular smooth muscle cells(VSMCs)induced by angiotensin II(AngⅡ),and its possible mechanism.Methods VSMCs were pretreated with Rut(0.3,1.0,3.0 μmol·L-1)for 10 min,then co-incubated with AngⅡ(1 μmol·L-1)for 24 h.The transient receptor potential vanilloid 1(TRPV1)competitive antagonist capsazepine(CAPZ,10 μmol·L-1)was used to investigate whether TRPV1 mediated the effects of Rut.Western blot was used to detect the protein levels of Cx43 and NF-κB p65 in VSMCs,and immunocytochemistry was applied to determine the nuclear translocation of p65.CCK-8 and EdU were used to detect the proliferation of VSMCs,and flow cytometry was employed to detect cell cycle distribution.Again,Western blot was used to assess the α-SMA and Calponin levels of contractile marker protein.Results Rut prevented the up-regulation of Cx43 and nuclear translocation of p65 induced by AngⅡ,and the effect was blocked by CAPZ.Rut prevented the proliferation of VSMCs induced by AngⅡ,as presented by inhibiting DNA synthesis and cell viability in VSMCs.Rut also prevented phenotypic switch of VSMCs induced by AngⅡ,and the effect could be partially blocked by CAPZ.Conclusion Rut reduces the expression of Cx43 and prevents the proliferation and phenotypic switch of VSMCs induced by AngⅡ,and its mechanism involves the TRPV1/NF-κB signaling pathway.

参考文献/References:

[1] Longchamp A,Allagnat F,Alonso F,et al.Connexin43 inhibition prevents human vein grafts intimal hyperplasia[J].PLoS One, 2015,10(9):e0138847.
[2] Alonso F,Krattinger N,Mazzolai L,et al.An angiotensin II- and NF-kappaB-dependent mechanism increases connexin 43 in murine arteries targeted by renin-dependent hypertension[J].Cardiovasc Res, 2010,87(1):166-76.
[3] Son J K,Chang H W,Jahng Y.Progress in studies on rutaecarpine.II.--Synthesis and structure-biological activity relationships[J].Molecules, 2015,20(6):10800-21.
[4] 刘 勇,余艳荣,彭维杰,等.吴茱萸次碱改善溶血性磷脂酰胆碱诱导的内皮细胞缝隙连接细胞间通讯功能障碍[J].中国药理学通报, 2013,29(11):1514-9.
[4] Liu Y,Yu Y R,Peng W J,et al.Rutaecarpine improves dysfunction of gap junctional intercellular communication induced by hemolytic phosphatidylcholine in endothelial cells[J].Chin Pharmacol Bull, 2013,29(11):1514-9.
[5] Peng W J,Liu Y,Yu Y R,et al.Rutaecarpine prevented dysfunction of endothelial gap junction induced by Ox-LDL via activation of TRPV1[J].Eur J Pharmacol, 2015,756:8-14.
[6] Qin X P,Zeng S Y,Tian H H,et al.Involvement of prolylcarboxypeptidase in the effect of rutaecarpine on the regression of mesenteric artery hypertrophy in renovascular hypertensive rats[J].Clin Exp Pharmacol Physiol,2009,36(3):319-24.
[7] 李艳菊,张 锋,龚其海,等.吴茱萸次碱抑制血管紧张素Ⅱ诱导的大鼠血管平滑肌细胞增殖[J].中国结合医学杂志,2014,20(9):682-7.
[7] Li Y J,Zhang F,Gong Q H,et al.Rutaecarpine inhibits angiotensin II-induced proliferation in rat vascular smooth muscle cells[J].Chin J Integr Med, 2014,20(9):682-7.
[8] Shi Y,Hou X,Zhang X,et al.Inhibition of oxidized-phospholipid-induced vascular smooth muscle cell proliferation by resveratrol is associated with reducing Cx43 phosphorylation[J].J Agric Food Chem, 2013,61(44):10534-41.
[9] Lin Y C,Chiang C H,Chang L T,et al.Simvastatin attenuates the additive effects of TNF-alpha and IL-18 on the connexin 43 up-regulation and over-proliferation of cultured aortic smooth muscle cells[J].Cytokine, 2013,62(3):341-51.
[10] Jia G,Cheng G,Gangahar D M,et al.Involvement of connexin 43 in angiotensin Ⅱ-induced migration and proliferation of saphenous vein smooth muscle cells via the MAPK-AP-1 signaling pathway[J].J Mol Cell Cardiol,2008,44(5):882-90.
[11] Wang S,Yamamoto S,Kogure Y,et al.Partial activation and inhibition of TRPV1 channels by evodiamine and rutaecarpine,two major components of the fruits of Evodia rutaecarpa[J].J Nat Prod, 2016,79(5):1225-30.
[12] Jia S,Hu C.Pharmacological effects of rutaecarpine as a cardiovascular protective agent[J].Molecules, 2010,15(3):1873-81.
[13] Li H,Xiang Y,Fan L J,et al.Myocardin inhibited the gap protein connexin 43 via promoted miR-206 to regulate vascular smooth muscle cell phenotypic switch[J].Gene, 2017,616:22-30.
[14] Zhang X,Wang X,Zhou X,et al.Phenotypic transformation of smooth muscle cells from porcine coronary arteries is associated with connexin 43[J].Mol Med Rep, 2016,14(1):41-8.

相似文献/References:

[1]聂绪强,俞林花,陈怀红,等.吴茱萸次碱对2型糖尿病肥胖大鼠的干预作用[J].中国药理学通报,2010,(07):872.
 NIE Xu qiang,YU Lin hua,CHEN Huai hong,et al.Intervention effects of rutaecarpine in type 2 diabetic obese rats[J].Chinese Pharmacological Bulletin,2010,(08):872.
[2]刘勇,余艳荣,彭维杰,等.吴茱萸次碱改善溶血性磷脂酰胆碱诱导的内皮细胞缝隙连接细胞间通讯功能障碍[J].中国药理学通报,2013,(11):1514.
 LIU Yong,YU Yan rong,PENG Wei jie,et al.Rutaecarpine prevents the disfunction of gap junction intercellular communication induced by LPC in endothelial cells[J].Chinese Pharmacological Bulletin,2013,(08):1514.
[3]骆 敏,罗燕妹,覃贵慧,等.缝隙连接蛋白43对人非小细胞肺癌HCC827细胞吉非替尼获得性耐药机制的初步研究[J].中国药理学通报,2016,(11):1510.[doi:10.3969/j.issn.1001-1978.2016.11.007]
 LUO-Min,LUO Yan-mei,QIN Gui-hui,et al.Effect of Cx43 on acquired gefitinib-resistance mechanisms in human NSCLC HCC827 cells[J].Chinese Pharmacological Bulletin,2016,(08):1510.[doi:10.3969/j.issn.1001-1978.2016.11.007]
[4]张 坤,秦小江,侯晓敏,等.杜鹃素通过降低Cx43的表达抑制AngⅡ诱导的VSMCs增殖[J].中国药理学通报,2018,(03):401.[doi:10.3969/j.issn.1001-1978.2018.03.020]
 ZHANG Kun,QIN Xiao-jiang,HOU Xiao-min,et al.Farrerol inhibits AngII-induced VSMCs proliferation by reducing Cx43 expression[J].Chinese Pharmacological Bulletin,2018,(08):401.[doi:10.3969/j.issn.1001-1978.2018.03.020]

备注/Memo

备注/Memo:
收稿日期:2018-04-17,修回日期:2018-05-20
基金项目:国家自然科学基金资助项目(No 81360493); 江西省自然科学基金资助项目(No 20161BAB215205)
作者简介:汪小英(1991-),女,硕士生,研究方向:心血管药理学,E-mail:1554958443@qq.com;
罗 丹(1979-),女,博士,教授,硕士生导师,研究方向:心血管药理学,通讯作者,E-mail:thinker_20080502@126.com
更新日期/Last Update: 2018-07-26