Ginsenoside Rg1 inhibits vascular intimal hyperplasia in balloon-injured rat carotid artery by down-regulation of extracellular signal-regulated kinase 2
Ginsenoside Rg1 inhibits vascular intimal hyperplasia in balloon-injured rat carotid artery by down-regulation of extracellular signal-regulated kinase 2
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DOI：
10.1016/j.jep.2011.09.029
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发表时间：
2011-11-18
影响因子：
5.4
通讯作者：
Huang, Xie-Nan
中科院分区：
文献类型：
--
作者：
Gao, Yang;Deng, Jiang;Huang, Xie-Nan
民族药理意义：人参皂苷Rg1是著名中草药人参的主要活性成分之一。已证实其在体外可抑制肿瘤坏死因子-a诱导的血管平滑肌细胞(VSMCs)的增殖。本研究旨在探讨Rg1对大鼠颈总动脉球囊损伤后血管新生内膜增生的影响。材料与方法：雄性SD大鼠颈总动脉(CCA)球囊导管摩擦内皮细胞建立动物模型。模型组和假手术对照组大鼠腹腔注射蒸馏水，其他球囊损伤组分别给予Rg1 4，8，16 mg/kg/d。连续14天后，CCA的组织病理学改变和VSMCs增殖的标记物--增殖细胞核抗原的变化证实了血管内膜的增生。免疫组织化学方法检测细胞增殖细胞核抗原、磷酸化细胞外信号调节蛋白2(p-ERK2)和丝裂原活化蛋白激酶磷酸酶-1(MKP-1)的表达，实时荧光定量RT-PCR法检测原癌基因(c-fos)、ERK2和平滑肌α-肌动蛋白(SM-α-actin)的表达。结果：Rg1能明显改善CCA的组织病理学改变，减少内皮摩擦诱导的PCNA蛋白表达；Rg1还可显著降低血管壁p-ERK2蛋白、ERK2和c-fos的表达，上调MKP-1的表达，从而使丝裂原活化的蛋白激酶途径失活。结论：Rg1可抑制球囊损伤诱导的血管新生内膜增生，其机制可能与抑制ERK2信号转导通路有关，且至少部分与MKP-1表达增加有关。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
Ethnopharmacological relevance: Ginsenoside Rg1 (Rg1) is one of the main active components of Panax ginseng a well-known herbal medicine. It has been demonstrated to inhibit proliferation of vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-a in vitro. The present study is aimed to examine the possible effects of Rg1 on vascular neointimal hyperplasia in balloon-injured carotid artery of rats in vivo.Materials and methods: The animal model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of male Sprague Dawley rats. Then the rats were intraperitoneally injected with distilled water in model group and sham operation control, or with Rg1 4, 8 and 16 mg/kg/d in other balloon injured groups. After consecutive 14 days, the vascular intimal hyperplasia was evidenced by histopathological alterations of the CCA and by changes observed in the marker of the proliferation of VSMCs-the proliferating cell nuclear antigen (PCNA). The protein expressions of PCNA and the phosphorylated extracellular signal-regulated kinase2 (p-ERK2) as well as mitogen-ativated protein kinase phosphatase-1 (MKP-1) were examined by immunohistochemistry; while the expressions of proto-oncogene (c-fos), ERK2 and smooth muscle alpha-actin (SM alpha-actin) mRNA were analyzed by Real-Time RT-PCR.Results: Rg1 administration could significantly ameliorate the histopathology of CCA and decrease the protein expression of PCNA induced by endothelia rubbing; and Rg1 medication also significantly decreased the expressions of p-ERK2 protein, ERK2 and c-fos mRNA in vessel wall, but up-regulated the MKP-1 expression, which was reported to inactivate mitogen-ativated protein kinase pathway. Furthermore, Rg1 could elevate the decreased SM a-actin mRNA expression induced by balloon injury.Conclusions: Rg1 can suppress the vascular neointimal hyperplasia induced by balloon injury, the mechanism may be involved in the inhibition on ERK2 signaling, and related, at least partly, to the increase in MKP-1 expression. (C) 2011 Elsevier Ireland Ltd. All rights reserved.