黄芪和当归配伍对大鼠血管内膜增生血管平滑肌细胞增殖的影响

doi:10.12092/j.issn.1009-2501.2018.04.001

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (4): 361-369.doi: 10.12092/j.issn.1009-2501.2018.04.001

• 基础研究 • 下一篇

黄芪和当归配伍对大鼠血管内膜增生血管平滑肌细胞增殖的影响

阎卉芳¹，徐昊¹，彭熙炜²，朱嘉欢¹，邓常清¹

¹湖南中医药大学，中西医结合心脑疾病防治湖南省重点实验室，长沙 410208，湖南; ²湖南中医药大学附属常德医院心血管科，常德 415000，湖南

收稿日期:2017-09-29 修回日期:2017-11-22 出版日期:2018-04-26 发布日期:2018-04-13
通讯作者: 邓常清，男，博士，教授，博士研究生导师，研究方向：心脑血管疾病防治及中药配伍原理。 Tel：0731-88459426 E-mail：dchangq@sohu.com
作者简介:阎卉芳，女，在读博士研究生，讲师，研究方向：中医药防治心脑血管疾病。 Tel：13974992433 E-mail：35154483@qq.com 徐昊，共同第一作者，男，在读硕士研究生，研究方向：中医药防治心脑血管疾病。 Tel：18711133835 E-mail：973624161@qq.com
基金资助:
国家自然科学基金面上项目（81473581）；“中西医结合防治心脑血管疾病的相关基础研究”湖南省科技创新团队（2013年）；“中医药防治心脑血管疾病基础研究”湖南省自然科学创新群体基金（2013年）

Effects of Astragalus-Angelica combination on VSMC proliferation of vascular intimal hyperplasia in rats

YAN Huifang¹, XU Hao¹, PENG Xiwei ², ZHU Jiahuan¹, DENG Changqing¹

¹ Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Disease, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China; ² Department of Cardiology, Affiliated Changde Hospital of Hunan University of Chinese Medicine, Changde 415000, Hunan, China

Received:2017-09-29 Revised:2017-11-22 Online:2018-04-26 Published:2018-04-13

摘要/Abstract

摘要：

目的: 探讨黄芪和当归不同配伍对大鼠血管内皮损伤后血管内膜增生中血管平滑肌细胞(VSMC)表型转化、细胞周期和磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号途径的影响。方法: 雄性大鼠制备腹主动脉球囊导管损伤血管内皮模型，设计黄芪和当归单用及不同比例配伍，对内皮损伤模型大鼠灌胃给药，干预14 d后取腹主动脉，检测腹主动脉增生内膜中VSMC表型转化、细胞周期相关蛋白表达和PI3K/Akt信号通路相关蛋白的表达。结果: 球囊导管损伤主动脉内皮后，可引起VSMC表型转化及VSMC增殖从而导致血管内膜增生。当归、黄芪、黄芪-当归1∶1配伍、黄芪-当归5∶1配伍可增强血管增生内膜中平滑肌α肌动蛋白（SM α-actin)表达，抑制增生内膜中增殖细胞核抗原（PCNA）蛋白表达。当归、黄芪、黄芪-当归1∶1配伍、黄芪-当归5∶1配伍可抑制血管组织中cyclin D1、cyclin E表达的增高，抑制增生内膜中p-PI3K和p-Akt蛋白表达的升高。结论: 黄芪当归配伍对血管内皮受损后内膜增生具有抑制作用，其作用可能与其通过抑制血管内皮受损后PI3K/Akt信号通路激活，进而抑制VSMC表型转化和细胞增殖，从而发挥抗VSMC增殖的作用有关。

关键词: 黄芪, 当归, 血管平滑肌细胞, 细胞周期, 磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）

Abstract:

AIM: To investigate the effects of different Astragalus-Angelica combination on vascular smooth muscle cells (VSMC) phenotype transformation, cell cycle and PI3K/AKT signal pathway of vascular intimal hyperplasia in rats. METHODS: A model of intimal hyperplasia of thoracoabdominal aorta was established by balloon catheter injury in male Sprague-Dawley rat, and the model rats were administrated Astragalus and Angelica with single use or different ratios for 14 days by means of intragastric administration. Then the thoracoabdominal aorta was taken out to analyze the pathological changes of the VSMC, expression of cell cycle and PI3K/Akt signaling pathway related proteins in hyperplastic intima. RESULTS: After balloon injury of aortic endothelium, VSMC phenotype transformation and proliferation can be induced, resulting in intimal hyperplasia. In hyperplastic intima, the expression of SM-actin can be enhanced and the expression of PCNA can be inhibited by the Astragalus and Angelica with single use and Astragalus-Angelica of 1∶1 and 5∶1 combination. The increased expression of cyclinD1 or cyclinE in damaged blood vessels and p-PI3K or p-Akt protein in hyperplastic intima can be inhibited by the Astragalus and Angelica with single use and Astragalus-Angelica of 1∶1 and 5∶1 combination. CONCLUSION: Vascular intimal hyperplasia can be inhibited by Astragalus-Angelica compatilibity. The mechanism may be related to the inhibition of PI3K/Akt signaling pathway activation, which lead to the inhibition of the phenotypic transformation and cell proliferation of VSMC, and then play the role of anti VSMC proliferation.

Key words: Astragalus, Angelica, VSMC, cell cycle, PI3K/Akt

中图分类号:

R965.2

阎卉芳，徐昊，彭熙炜，朱嘉欢，邓常清. 黄芪和当归配伍对大鼠血管内膜增生血管平滑肌细胞增殖的影响[J]. 中国临床药理学与治疗学, 2018, 23(4): 361-369.

YAN Huifang, XU Hao, PENG Xiwei, ZHU Jiahuan, DENG Changqing. Effects of Astragalus-Angelica combination on VSMC proliferation of vascular intimal hyperplasia in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(4): 361-369.

参考文献

［1］Bulum J, Ernst A, Strozzi M. The impact of successful manual thrombus aspiration on in-stent restenosis after primary PCI：angiographic and clinical follow-up［J］. Coron Artery Dis, 2012,23(23): 487-491.
［2］Song M, Shen HT, Cui JJ, et al. A novel model of intimal hyperplasia with graded hypoosmotic damage［J］.Cardiovasc Pathol,2012,21(6): 490-498.
［3］Alexand MR, Owens GK. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease［J］. Annu Rev Physiol, 2012,74: 13-40.
［4］Yang X, Huang CG, Du SY, et al. Effect of Danggui Buxue Tang on immune-mediated aplastic anemia bone marrow proliferation mice［J］. Phytomedicine, 2014,21(5): 640-646.
［5］Li YD, Ma YH, Zhao JX, et al. Protection of ultra-filtration extract from Danggui Buxue Decoction on oxidative damage in cardiomyocytes of neonatal rats and its mechanism［J］. Chin J Integr Med, 2011,17(11): 854-859.
［6］张志斌,陆曙,周春刚,等.当归补血汤对大鼠动脉内皮细胞凋亡的干预作用［J］.中国实验方剂学杂志,2013,19(3): 215-218.
［7］秦瑧,黄水清.当归补血汤对动脉样硬化兔内皮祖细胞及血清VEGF、SDF-1的影响［J］.中国病理生理杂志,2012,28(2): 211-215.
［8］Li F, Tang R, Chen LB, et al. Effects of astragalus combined with angelica on bone marrow hematopoiesis suppression induced by cyclophosphamide in mice［J］. Biol Pharm Bull, 2017, 40(5): 598-609.
［9］彭熙炜,阎卉芳,黄娟,等. 黄芪-当归不同配伍比例对大鼠血管内膜增生的影响［J］. 中国中医药信息杂志,2017,24(6):56-59.
［10］Wu L, Zhang W, Li H, et al. Inhibition of aortic intimal hyperplasia and cell cycle protein and extracellular matrix protein expressions by BuYang HuanWu Decoction［J］.J Ethnopharmacol, 2009,125(3): 423-435.
［11］Wu L, Zhang W, Tang YH, et al. Effect of total saponins of "panax notoginseng root" on aortic intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix in rats［J］. Phytomedcine, 2010,17(3/4):233-240.
［12］Watson T，Goon PK，Lip GY. Endothelial progenitor cells, endothelial dysfunction, inflammation and oxidative stress in hypertension［J］. Antioxid Redox Sign, 2008, 10(8): 1079-1088.
［13］Bae JH, Bassenge E, Kim KY, et al. Effects of low-dose atorvastatin on vascular responses in patients undergoing percutaneous coronary intervention with stenting［J］. J Cardiovasc Pharmacol Ther, 2004, 9(3): 185-192.
［14］Faries PL, Rohan DI, Wyers MC, et al. Vascular smooth muscle cells derived from atherosclerotic human arteries exhibit greater adhesion, migration, and proliferation than venous cells［J］.J Surg Res, 2002,104(1):22-28.
［15］Regan CP, Adam PJ, Madsen CS, et al. Molecular mechanisms of decreased smooth muscle differentiation marker expression after vascular injury［J］. J Clin I nvest, 2000, 106(9):1139-1147.
［16］Miniati DN, Hoyt EG, Feeley BT, et al. Ex vivo antisense oligonucleotides to proliferating cell nuclear antigen and Cdc2 kinase inhibit graft coronary artery disease［J］. Circulation, 2000, 102(3): 237-242.
［17］Xiao B, Spencer J, Clements A, et al. Crystal structure of the retinoblastoma tumor suppressor protein bound to E2F and themolecular basis of its regulation［J］. Proc Natl Acad Sci USA,2003,100(5): 2363-2368．
［18］Mehta RR, Yamada T, Taylor BN, et al. A cell penetrating peptide derived from azurin inhibits angiogenesis and tumor growth by inhibiting phosphorylation of VEGFR-2, FAK and Akt［J］. Angiogenesis,2011,14(3)：355-369.
［19］Morello F, Perino A, Hirsch E. Phosphoinositide 3-kinase signalling in the vascular system［J］. Cardiovasc Res, 2009, 82(2):261-271.

[1]	马仙康, 杨丽霞, 崔阳阳, 米登海. 当归多糖通过抑制GRP78、p-PERK、p-Eif2α表达改善糖尿病KK-Ay小鼠肝内质网应激[J]. 中国临床药理学与治疗学, 2023, 28(8): 926-936.
[2]	王鑫昱, 陈亦鹏, 马永力, 何君妃. “杜仲-当归”调控NLPR3炎症小体对骨关节炎大鼠改善作用的研究[J]. 中国临床药理学与治疗学, 2023, 28(7): 751-757.
[3]	贾成文, 蒋虎刚, 高翔, 韩金晏, 徐晓东, 赵信科. 当归红芪超滤物对miR-21-5P靶向调控TGF-β1介导放射性心肌纤维化的干预效应[J]. 中国临床药理学与治疗学, 2022, 27(11): 1221-1230.
[4]	叶凯丽, 郑雯, 叶啟发, 杨岚. CDK1参与肝细胞癌的发展机制及其抑制剂应用价值[J]. 中国临床药理学与治疗学, 2021, 26(9): 1086-1094.
[5]	聂娟，曹玉梅，杨冬梅，孙四玉，王巧琼，谢雪姣，庹勤慧. 夏枯草水提取物对血管平滑肌细胞增殖的影响及其机制研究[J]. 中国临床药理学与治疗学, 2019, 24(9): 977-982.
[6]	吴丽梅，程丽艳，郑晓亮，王孝举. 靶向抑制CDK4/6的肿瘤治疗基础研究与临床应用进展[J]. 中国临床药理学与治疗学, 2019, 24(9): 1065-1069.
[7]	邹照银，郑府，徐先顺，丁文娟，陈艳，蒲道静. 黄芪甲苷通过SDF-1/CXCR4信号通路诱导人肾腺癌细胞的凋亡[J]. 中国临床药理学与治疗学, 2019, 24(6): 665-669.
[8]	余静，赵海岚，程凯尧，沈平宇，金黄林. 黄芪皂苷通过调控蛋白激酶R样内质网激酶途径抑制高糖诱导的人视网膜色素上皮细胞自噬的研究[J]. 中国临床药理学与治疗学, 2019, 24(4): 361-368.
[9]	邱飞, 高丹, 杨冬梅, 钟小妹, 唐莎, 尹辉明, 张在其. 姜黄素对血小板源性生长因子诱导的血管平滑肌细胞增殖及PTEN表达的影响[J]. 中国临床药理学与治疗学, 2019, 24(12): 1358-1363.
[10]	秦博宇，王刚，齐晓光，王雅捷，孙琼，孙胜杰 . 顺铂与唑来膦酸序贯应用抑制肺癌细胞增殖的研究[J]. 中国临床药理学与治疗学, 2018, 23(9): 1027-1030.
[11]	颜为红，邹坤，贺海波，张永峰，李小妹，李小琴，杨小姣，汪鋆植，邓张双. 吉祥草中甾体皂苷RCE-4对人宫颈癌Caski细胞Ras/Erk和p16/cyclinD1/CDK4通路的影响[J]. 中国临床药理学与治疗学, 2018, 23(3): 247-254.
[12]	李竹青，鞠营辉，陈清青，马可可，李卫平. 黄芪甲苷对糖尿病大鼠早期肾脏损伤的保护作用及其机制研究[J]. 中国临床药理学与治疗学, 2018, 23(3): 255-262.
[13]	周夏慧，王庆来，朱雪梅，潘蓉蓉，潘胜莲，朱方会，王丁，罗晓红. 当归多糖对DPN大鼠TLR4/MyD88/NF-κB通路抑制影响[J]. 中国临床药理学与治疗学, 2018, 23(12): 1340-1347.
[14]	张艳霞，蔺兴遥，安方玉，张正顺，陈绍仪，周佳玮，张延英. 当归挥发油对人肺腺癌GLC-82细胞增殖及凋亡的影响[J]. 中国临床药理学与治疗学, 2018, 23(1): 29-33.
[15]	张艳霞，张正顺，陈绍仪，孔学礼，周佳玮. 当归挥发油联合卡铂对人肺腺癌A549细胞增殖及凋亡的影响[J]. 中国临床药理学与治疗学, 2017, 22(7): 755-761.

黄芪和当归配伍对大鼠血管内膜增生血管平滑肌细胞增殖的影响

Effects of Astragalus-Angelica combination on VSMC proliferation of vascular intimal hyperplasia in rats

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价