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黄芪皂苷III抑制小鼠动脉平滑肌细胞TNFR1介导信号转导(PDF)

《云南中医学院学报》[ISSN:1000-2723/CN:53-1048/R]

期数:
2017年03期
页码:
1-6
栏目:
实验研究
出版日期:
2017-07-17

文章信息/Info

Title:
Inhibition of Astragaloside III on TNFR1-mediated Signaling Pathwaysin Mouse Arterial Smooth Muscle Cells
作者:
王海芳1张琳萍2霍雪萍1赵向绒1赵苗苗1曹情雯3胡军1刘勤社4
1. 陕西省人民医院中心实验室,陕西 西安 710068; 2. 西安交通大学医学部,陕西 西安 710061;3. 陕西省中医医院急诊科,陕西 西安 710003; 4. 陕西中医药大学,陕西 西安 712046
Author(s):
WANG Haifang1ZHANG Linping2HUO Xueping1ZHAO Xiangrong1ZHAO Miaomiao1CAO Qingwen3HU Jun1LIU Qinshe4
1. Laboratory Center of Shaanxi Province People’s Hospital, Xi’an 710068, China;2. Medical School of Xi’an JiaoTong University, Xi’an 710061, China;3. Department of Emergency, Shaanxi Province Hospital of Chinese Medicine, Xi’an 710003, China;4. University of Traditional Chinese Medicine, Xi’an 712046, China
关键词:
黄芪皂苷Ⅲ 动脉平滑肌细胞 肿瘤坏死因子-α TNFR1 NF-κB 抗炎作用
Keywords:
astragaloside III arterial smooth muscle cells tumor necrosis factor-α TNFR1 NF-κB anti-inflammatory effect
分类号:
R285.5
DOI:
10.19288/j.cnki.issn.1000-2723.2017.03.001
文献标识码:
A
摘要:
目的 研究黄芪皂苷III(astragaloside III,ASⅢ)对小鼠动脉平滑肌细胞(arterial smooth muscle cells,ASMCs)中I型TNF-α受体(TNF-α receptor type 1,TNFR1)介导信号通路的抑制作用,为中药黄芪的抗炎作用和抗动脉粥样硬化作用提供证据。方法 以不同浓度ASⅢ预处理ASMCs,之后以TNF-α诱导细胞。采用WST-1实验检测细胞活力变化;采用实时定量RT-PCR技术检测细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)、凝集素样氧化低密度脂蛋白受体(lectin-like oxidized LDL receptor-1,Lox-1)和ATP结合盒转运蛋白A1(ATP-binding cassette transporter A1,ABCA1)mRNA表达变化;采用Western Blot方法检测ICAM-1、Lox-1和ABCA1蛋白表达变化,并检测ASⅢ对转录因子NF-κB(nuclear factor-κB)上游抑制蛋白IκBα(NF-κB inhibitor-α)、以及对信号分子AKT、细胞外受体活化激酶(extracellular receptor-activated kinases,ERKs)和p38磷酸化的影响。结果 (1)ASⅢ在30 nM~10 μM范围内不抑制细胞活力;(2)ASⅢ剂量依赖性抑制TNF-α对ICAM-1、Lox-1和ABCA1 mRNA表达的调控;(3)ASⅢ剂量依赖性抑制TNF-α对ICAM-1、Lox-1和ABCA1 蛋白表达的调控;(4)ASⅢ显著抑制TNFR1介导的IκBα磷酸化和降解;(5)ASⅢ显著抑制TNFR1介导的AKT、ERKs和p38磷酸化。结论 ASⅢ可全面抑制ASMCs中TNFR1介导信号通路激活,参与其抗炎和抗动脉粥样硬化作用。
Abstract:
Objective To investigate the inhibitory effect of astragaloside III(ASIII) on TNFR1-mediated signaling pathways in mouse arterial smooth muscle cells(ASMCs) and provide experimental evidence for the anti-inflammatory and anti-atherosclerotic actions of Chinese herbal medicine Radix Astragali(Huangqi). Methods The effect of ASIII on the cell viability of ASMCs was evaluated by conducting a WST-1 assay. The mRNA levels of ICAM-1(intercellular adhesion molecule-1), Lox-1(lectin-like oxidized LDL receptor-1) and ABCA1(ATP-binding cassette transporter A1) in ASMCs were measured using quantitative RT-PCR technique. Western Blot was performed to detect the effect of ASIII on TNF-α-induced modulation of ICAM-1, Lox-1 and ABCA1 protein levels. TNFR1-mediated phosphorylation and degradation of I Bα, and phosphorylation of AKT, ERKs and p38 were also measured by using Western Blot analysis. Results (1) ASIII, when used at a concentration between 30 nM and 10 μM, did not reduce the cell viability of ASMCs; (2) The TNFα-stimulated up-regulation of ICAM-1 and Lox-1, and down-regulation of ABCA1 expression level were inhibited by ASIII in a concentration-dependent manner; (3) ASIII suppressed the TNFR1-mediated phosphorylation and degradation of IκBα protein; (4) ASIII suppressed TNFR1-mediated phosphorylation of AKT, ERKs and p38. Conclusion ASIII inhibits the TNFR1-mediated intracellular signaling pathways in ASMCs, which may in part explain its anti-inflammatory and anti-antherosclerostic effects.

参考文献/References

[1] 黄玫,曲晶,李晓天,等. 黄芪化学成分及对心血管系统作用的研究进展[J]. 中国老年学杂志,2009,29(11):1451-1453.
[2] 王海芳,曹情雯,王娜娜,等. 黄芪注射液和黄芪总皂苷注射液治疗冠心病心绞痛临床疗效的系统评价[J]. 云南中医学院学报,2017,40(1):22-27.
[3] Lee DY,Noh HJ,Choi J,et al. Anti-inflammatory cycloartane-type saponins of Astragalus membranaceus[J]. Molecules,2013,18(4):3725-3732.
[4] Zhang H,Park Y,Wu J,et al. Role of TNF-α in vascular dysfunction[J]. Clin Sci(Lond),2009,116(Pt3):219-230.
[5] Zhang L,Connelly JJ,Peppel K,et al. Aging-related atherosclerosis is exacerbated by arterial expression of tumor necrosis factor receptor-1:evidence from mouse models and human association studies[J]. Hum Mol Genet,2010,19(14):2754-2766.
[6] Liu QS,Wang HF,Sun AK,et al. A comparative study on inhibition of total astragalus saponins and astragaloside IV on TNFR1-mediated signaling pathways in arterial endothelial cells[J]. PLoS one,2014,9(7):e101504.
[7] Kroetsch JT,Levy AS,Zhang H,et al. Constitutive smooth muscle tumour necrosis factor regulates microvascular myogenic responsiveness and systemic blood pressure[J]. Nat Commun,2017(8):14805.
[8] 赵苗苗,王海芳,曹情雯,等. 中药活性成分对oxLDL诱导血管平滑肌细胞泡沫化的影响[J]. 中西医结合心脑血管病杂志,2017,15(3):310-313.
[9] Chen G,Goeddel DV. TNF-R1 signaling:a beautiful pathway[J]. Science,2002,296(5573):1634-1635.
[10] Broekman W,Amatngalim GD,de Mooij-Eijk Y,et al. TNF-α and IL-1β-activated human mesenchymal stromal cells increase airway epithelial wound healing in vitro via activation of the epidermal growth factor receptor[J]. Respir Res,2016,17(1):3.
[11] Potera RM,Jensen MJ,Hilkin BM,et al. Neutrophil azurophilic granule exocytosis is primed by TNF-α and partially regulated by NADPH oxidase[J]. Innate Immun,2016,22(8):635-646.
[12] Lin CP,Huang PH,Lai CF,et al. Simvastatin Attenuates Oxidative Stress,NF-κB Activation,and Artery Calcification in LDLR-/-Mice Fed with High Fat Diet Via Down-regulation of Tumor Necrosis Factor-α and TNF Receptor 1[J]. PLoS One,2015,10(12):e0143686.
[13] Wang SM,Tang LL,Chen FY. Astragaloside III from Astragalus membranaceus antagonizes breast cancer growth[J]. Afr J Tradit Complem,2015,12(3):183.
[14] 万春平. 黄芪皂苷III通过IFN-γ介导体外免疫调节作用的研究[J]. 云南中医中药杂志,2011,32(9):69-71.
[15] Liu XH,Guo L,Yang YL,et al. Development and Validation of a Rapid and Simple UPLC-ESI-MS Method for Pharmacokinetics and Tissue Distribution of Astragaloside III in Rats[J]. J Chromatogr Sci,2016,54(5):811-818.
[16] 史静超,李浩铮,王永辉,等. 不同产地蒙古黄芪中黄芪甲苷、黄芪皂苷Ⅰ、黄芪皂苷II和黄芪皂苷III含量的比较与分析[J]. 世界科学技术-中医药现代化,2015,17(5):1016-1021.

备注/Memo

备注/Memo:
* 基金项目: 国家自然科学基金面上项目(81573823)
收稿日期: 2017 - 04- 28
作者简介: 王海芳(1972-),女,山西阳泉人,博士,助理研究员,研究方向:中药抗动脉粥样硬化分子机制。
△通信作者:刘勤社,E-mail:lqsspph@126.com
更新日期/Last Update: 2017-06-20