| 基于主动脉Ang Ⅱ/AT1通路研究蒙花苷对高血压血管重构的影响 |
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| 引用本文： | 苏洁,俞静静,颜美秋,王婷,许韩婷,吴亚军,陈素红,吕圭源.基于主动脉Ang Ⅱ/AT1通路研究蒙花苷对高血压血管重构的影响[J].中草药,2019,50(20):5003-5010. |
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| 作者姓名： | 苏洁 俞静静 颜美秋 王婷 许韩婷 吴亚军 陈素红 吕圭源 |
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| 作者单位： | 浙江中医药大学, 浙江 杭州 310053,浙江中医药大学, 浙江 杭州 310053,浙江中医药大学, 浙江 杭州 310053,浙江中医药大学, 浙江 杭州 310053,浙江中医药大学, 浙江 杭州 310053,浙江中医药大学, 浙江 杭州 310053,浙江工业大学, 浙江 杭州 310014,浙江中医药大学, 浙江 杭州 310053 |
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| 基金项目： | 浙江省自然科学基金项目（LQ18H280003）；国家自然科学基金资助项目（81873036）；浙江省自然科学基金项目（LQ17H280004）；浙江省自然科学基金项目（LQ17H280005）；国家自然科学基金资助项目（81803819）；浙江省重点研发计划（2017C03052）；浙江重点实验室（2012E10002） |
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| 摘 要： | 目的基于主动脉血管紧张素Ⅱ(Ang Ⅱ)/血管紧张素受体1型(AT1)通路研究蒙花苷对高血压大鼠血管重构的影响。方法采用自发性高血压大鼠(SHR)自然形成高血压血管重构模型,观察蒙花苷对SHR血压、眩晕时间、主动脉组织形态学及胶原纤维分布的影响。采用Ang Ⅱ诱导原代血管平滑肌细胞(VSMCs)建立体外血管重构模型,通过MTT和结晶紫实验观察蒙花苷对VSMCs异常增殖的影响,通过细胞划痕及小室实验观察其对VSMCs迁移的影响;检测Ang Ⅱ/AT1信号通路相关分子Ang Ⅱ、AT1、基质金属蛋白酶-2(MMP-2)、MMP-9、Src、p-Src、Syk和p-Syk蛋白表达。结果蒙花苷能明显缩短SHR眩晕时间及降低SBP、DBP及MBP水平,并能改善主动脉中膜增厚、VSMCs增生肥大且排列紊乱等,减少主动脉中膜胶原纤维分布;能显著抑制Ang Ⅱ诱导的VSMCs异常增殖和迁移;能抑制活性氧(ROS)的产生,降低Ang Ⅱ、AT1、MMP-2、MMP-9和p-Src的蛋白表达水平。结论蒙花苷可能是通过抑制主动脉中AngⅡ/AT1信号通路的活化,继而抑制血管平滑肌细胞的异常增殖和迁移,从而起到抗高血压血管重构的作用。
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| 关 键 词： | 高血压 血管重构 蒙花苷 血管紧张素II 血管紧张素受体1型 基质金属蛋白酶-2 |
| 收稿时间： | 2019/4/28 0:00:00 |
Effects of buddleoside on hypertensive vascular remodeling through Ang II/AT1 signaling pathway in aorta |
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| SU Jie,YU Jing-jing,YAN Mei-qiu,WANG Ting,XU Han-ting,WU Ya-jun,CHEN Su-hong and LV Gui-yuan.Effects of buddleoside on hypertensive vascular remodeling through Ang II/AT1 signaling pathway in aorta[J].Chinese Traditional and Herbal Drugs,2019,50(20):5003-5010. |
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| Authors: | SU Jie YU Jing-jing YAN Mei-qiu WANG Ting XU Han-ting WU Ya-jun CHEN Su-hong and LV Gui-yuan |
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| Institution: | Zhejiang Chinese Medical University, Hangzhou 310053, China,Zhejiang Chinese Medical University, Hangzhou 310053, China,Zhejiang Chinese Medical University, Hangzhou 310053, China,Zhejiang Chinese Medical University, Hangzhou 310053, China,Zhejiang Chinese Medical University, Hangzhou 310053, China,Zhejiang Chinese Medical University, Hangzhou 310053, China,Zhejiang University of Technology, Hangzhou 310014, China and Zhejiang Chinese Medical University, Hangzhou 310053, China |
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| Abstract: | Objective The aim of this paper was to observe the effects of buddleoside on hypertensive vascular remodeling through Ang II/AT1 signaling pathway in aorta. Methods We used SHR model to examine the blood pressure, vertigo time, histomorphology, and collagen fiber distribution of the aorta, and evaluate whether buddleoside could ameliorate the hypertensive vascular remodeling in vivo. Meanwhile, abnormal proliferation and migration of VSMCs induced by Ang II in vitro was used to identify the mechanism. The anti-proliferation effect of buddleoside in VSMCs was observed using MTT assay and crystal violet assay. The anti-migration effect in VSMCs was observed using monolayer-wounding and boyden chamber transwell assay. Furthermore, the protein expression of Ang II, AT1, MMP-2, MMP-9, Src, p-Src, Syk, and p-Syk were examined. Results The results showed that buddleoside could significantly decrease SBP, DBP, MBP, and vertigo time, and improve the thickened media aorta, hypertrophy and disordered arrangement of VSMCs, distribution of collagen fibers. Buddleoside could also inhibit the proliferation and migration of VSMCs, inhibit the ROS production, and reduce the protein expression of Ang II, AT1, MMP-2, MMP-9, Src, and p-Src. Conclusion These data supported that buddleoside can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of VSMCs. Its mechanism is mediated by the regulation of Ang II/AT1 signaling pathway. |
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| Keywords: | hypertension vascular remodeling buddleoside Ang II AT1 MMP-2 |
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