人参皂苷Re对球囊损伤所致大鼠颈动脉新生内膜增生及ERK通路的影响

高杨,杨洁,安勇刚,邓江,杨丹莉,黄燮南

中国药学杂志 ›› 2015, Vol. 50 ›› Issue (18) : 1589-1593.

PDF(878 KB)
PDF(878 KB)
中国药学杂志 ›› 2015, Vol. 50 ›› Issue (18) : 1589-1593. DOI: 10.11669/cpj.2015.18.003
论 著

人参皂苷Re对球囊损伤所致大鼠颈动脉新生内膜增生及ERK通路的影响

  • 高杨a,杨洁b,安勇刚b,邓江a,杨丹莉a,黄燮南a
作者信息 +

Inhibitory Effects of Ginsenoside Re on Vascular Neointimal Hyperplasia Induced by Balloon-Injury and ERK signaling in Rats

  • GAO Yanga, YANG Jieb, AN Yong-gangb, DENG Jianga, YANG Dan-lia, HUANG Xie-nana
Author information +
文章历史 +

摘要

目的 探讨人参皂苷Re (ginsenoside Re) 对球囊损伤所致血管新生内膜增生的作用及其分子机制。方法 利用雄性SD大鼠建立球囊损伤致颈动脉内膜增生模型,模型制备完成后后将40只大鼠随机分为5组:人参皂苷 Re 6、12、24 mgkg-1d-1剂量组、模型组及假手术组,每组8只,术后次日腹腔注射给药,模型组与假手术组给予等体积生理盐水,连续给药14 d后取损伤侧颈动脉行HE染色,观察颈动脉血管腔狭窄程度并计算新生内膜面积及内膜/中膜面积的比值;实时荧光定量聚合酶链反应法检测血管壁丝裂原活化蛋白激酶磷酸酶-1(mitogen-activated protein kinase phosphatase-1,MKP-1)mRNA的表达;免疫组织化学法检测血管壁丝裂原活化蛋白激酶磷酸酶-1和磷酸化细胞外信号调节激酶1/2(phosphorylation extracellular signal-regulated kinase,pERK1/2)蛋白质的表达。结果 与假手术组比较,模型组血管腔明显狭窄 (P<0.01),血管壁磷酸化细胞外信号调节激酶1/2蛋白质表达明显上调,而丝裂原活化蛋白激酶磷酸酶-1 mRNA及蛋白质表达却明显下调;人参皂苷Re各给药组均能改善球囊损伤所致的血管狭窄,使血管壁新生内膜面积、新生内膜/中膜面积的比值明显减小(P<0.05),并逆转球囊损伤后磷酸化细胞外信号调节激酶1/2蛋白质表达(P<0.05)和丝裂原活化蛋白激酶磷酸酶-1 mRNA及蛋白质表达(P<0.05,P<0.01)。结论 人参皂苷Re可抑制球囊损伤所致的颈动脉狭窄,其分子机制与抑制ERK通路有关。

Abstract

OBJECTIVE To investigate the inhibitory effect of ginsenoside Re on vascular neointimal hyperplasia induced by balloon-injury and probe its molecular mechanism in rats. METHODS The rat carotid artery neointimal hyperplasia model was established by rubbing the endothelia with a balloon in male Sprague-Dawley rats, then animals were intrapritoneally injected with distilled water in model group and sham operation group or with ginsenoside Re 6, 12 and 24 mgkg-1d-1 in other endothelia rubbed groups. After 14 consecutive days, the injuried artery was taken for H&E staining, the histopathological observation and detecting the neointimal area as well as the ratio of neointimal area/media area were taken to evaluate the vescular intimal hyperplasia level. For probing the molecular mechanism, the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) was detected at the transcript levels by real time RT-PCR, and the protein expressions of MKP-1 and phosphorylation extracellular signal-regulated kinase 1/2(pERK1/2) were examined by immunohistochemistry and analyzed with Image-Pro Plus.RESULTS Compared with the endothelia rubbing model group, ginsenoside Re 6, 12, 24 mgkg-1d-1 medications significantly improved the histopathological changes induced by baloon-injury, decreased the elevated neointimal area and the ratio of neointimal area/ media area induced by baloon-injury; ginsenoside Re administration could also down-regulate the elevated pERK1/2 protein expression, and significantly up-regulated the decreased MPK-1 mRNA and protein expressions induced by baloon-injury. CONCLUSION Ginsenoside Re inhibits the vascular neointimal hyperplasia induced by baloon- injury in rats, the molecular mechanism is related to its inhibition effect on ERK signaling.

关键词

人参皂苷Re / 球囊损伤 / 血管狭窄 / 细胞外信号调节激酶 / 丝裂原活化蛋白激酶磷酸酶-1

Key words

ginsenoside Re / balloon-injury / vascular neointimal hyperplasia / extracellular signal-regulated kinase 1/2 / mitogen-activated protein kinase phosphatase-1

引用本文

导出引用
高杨,杨洁,安勇刚,邓江,杨丹莉,黄燮南. 人参皂苷Re对球囊损伤所致大鼠颈动脉新生内膜增生及ERK通路的影响[J]. 中国药学杂志, 2015, 50(18): 1589-1593 https://doi.org/10.11669/cpj.2015.18.003
GAO Yang, YANG Jie, AN Yong-gang, DENG Jiang, YANG Dan-li, HUANG Xie-nan. Inhibitory Effects of Ginsenoside Re on Vascular Neointimal Hyperplasia Induced by Balloon-Injury and ERK signaling in Rats[J]. Chinese Pharmaceutical Journal, 2015, 50(18): 1589-1593 https://doi.org/10.11669/cpj.2015.18.003
中图分类号: R965   

参考文献

[1] ROBERTS P J, DER C J. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer [J]. Oncogene, 2007, 26 (22):3291-3310.
[2] GAO Y,DENG J,YU X F,et al.Ginsenoside Rg1 inhibits vascular intimal hyperplasia in balloon-injured rat carotid artery by downregulation of extracellular signal-regulated kinase 2 [J]. J Ethnopharmacol,2011,138(2):472-478.
[3] SHI W, WANG Y, LI J, et al. Investigation of ginsenosides in different parts and ages of Panax ginseng[J]. Food Chem, 2007, 102(3):664-668.
[4] CHEN Y J. The mechanism of coronary artery restenosis and prevention measures after PCI operation [J]. Jilin Med J (吉林医学), 2012, 33(33):7223-7224.
[5] LI Y, ZHANG T J, LIU S X, et al. A review on the ginseng chemical constituents and pharmacological [J]. Chin Tradit Herb Drugs (中草药), 2009, 40(1):164-166.
[6] MEISTER M, TOMASOVIC A, BANNING A, et al. Mitogen-activated protein (MAP) kinase scaffolding proteins: A recount [J]. Int J Mol Sci, 2013,14(3):4854-4884.
[7] LEE J H, JOHNSON P R, ROTH M, et al. ERK Activation and mitogenesis in human airway smooth muscle cells[J]. Am J Physiol Lung Cell Mol Physiol, 2001, 280(5):1019-1029.
[8] ROOVERS K, DAVEY G, ZHU X, et al. Alpha5beta1 integrin controls cyclin D1 expression by sustaining mitogen-activated protein kinase activity in growth factor-treated cells [J]. Mol Biol Cell, 1999, 10(10):3197-3204.
[9] ISENOVIC E R, KEDEES M H, TEPAVCEVIC S, et al. Role of PI3K/AKT, cPLA2 and ERK1/2 signaling pathways in insulin regulation of vascular smooth muscle cells proliferation [J]. Cardiovasc Hematol Disord Drug Targets,2009,9(3):172-180.
[10] METZLER B, LI C, HU Y, et al. LDL Stimulates mitogen-activated protein kinase phosphatase-1 expression, independent of LDL receptors, in vascular smooth muscle cells[J]. Arterioscler Thromb Vasc Biol, l999,19(8):1862-1871.
[11] CHAI S B, TANG Z S. The role of mitogen-activated protein kinase phosphatase in cardiovascular system [J]. Prog Physiol Sci (生理科学进展), 2000,31(3):240-242.
[12] SUN H, TONKS N K, BAR-SAGI D. Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1[J]. Science, 1994, 266(5183):285-288.

基金

国家自然科学基金资助项目(81360494);贵州省科学技术基金(黔科合J字LKZ[2010]31号);贵州省中医药管理局中医药、民族医药科学技术研究课题资助项目(QZYY2011-67) ;贵州省教育厅自然科学研究资助项目[黔教合KY(2012)080号]
PDF(878 KB)

Accesses

Citation

Detail

段落导航
相关文章

/