FOXO1参与高血压条件下异常张应变诱导的血管平滑肌细胞增殖

发布时间：2018-06-17 05:17

本文选题：高血压 + 周期性张应变　；参考：《医用生物力学》2014年05期

【摘要】：目的探讨高血压条件下异常升高的周期性张应变刺激对血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖的影响,以及Forkhead转录因子1(FOXO1)在其中可能的作用。方法构建腹主动脉缩窄高血压大鼠模型,并以假手术组为对照,应用FX-4000T体外周期性张应变加载系统,分别对VSMCs施加5%的生理性张应变和15%的高血压病理性张应变。Western blot检测VSMCs的FOXO1及p-FOXO1表达水平,Brd U法检测VSMCs增殖活性。RNA干扰技术抑制VSMCs的FOXO1表达,检测FOXO1、p-FOXO1表达以及VSMCs增殖活性变化。结果腹主动脉缩窄术后2和4周,大鼠血压较假手术大鼠明显增高。与假手术大鼠相比,高血压大鼠血管壁细胞增殖活性明显增高,同时FOXO1及p-FOXO1表达水平也显著性升高。细胞实验表明,与5%张应变组相比,15%张应变加载显著上调VSMCs的FOXO1、p-FOXO1表达水平,以及VSMCs增殖活性。静态条件下RNA干扰抑制VSMCs的FOXO1及p-FOXO1表达,VSMCs的增殖活性明显降低。结论高血压病理条件下,异常增高的周期性张应变可能通过促进FOXO1表达和磷酸化诱导VSMCs增殖。以动物模型观察现象,在细胞分子水平探讨机制,旨在明确FOXO1在高血压血管重建中的作用及其力学生物学机制,为阐明高血压血管重建的发病机理和药物治疗靶标的研究提供新的实验依据。
[Abstract]:Objective to investigate the effect of abnormal elevated cyclic tensile strain stimulation on the proliferation of vascular smooth muscle cells (VSMC) and the possible role of Forkhead transcription factor 1 (FOXO1) in the proliferation of vascular smooth muscle cells (VSMCs). Methods A rat model of abdominal aortic coarctation was established, and FX-4000T in vitro cyclic strain loading system was used as control group. The expression levels of FOXO1 and p-FOXO1 in VSMCs were detected by applying 5% physiological strain and 15% physiologic strain. Western blot was used to detect the expression level of FOXO1 and p-FOXO1 respectively. The expression of FOXO1, the expression of FOXO1p-FOXO1 and the changes of proliferative activity of VSMCs were detected by BrdU method. Results at 2 and 4 weeks after abdominal aortic coarctation, the blood pressure of rats was significantly higher than that of sham-operated rats. The proliferative activity of vascular parietal cells and the expression of FOXO1 and p-FOXO1 in hypertensive rats were significantly higher than those in sham-operated rats. Compared with 5% strain group, 15% strain loading significantly upregulated the expression level of FOXO1 p-FOXO1 and the proliferative activity of VSMCs. Under static condition, RNA interference inhibited the proliferation activity of VSMCs expressed in FOXO1 and p-FOXO1. Conclusion the abnormal increase of cyclic tensile strain may induce the proliferation of VSMCs by promoting FOXO1 expression and phosphorylation under pathological conditions of hypertension. In order to clarify the role of FOXO1 in vascular remodeling of hypertension and its mechanism of mechanics and biology, we observed the phenomena in animal models and explored the mechanism at the cellular and molecular level. It provides a new experimental basis for elucidating the pathogenesis of vascular remodeling of hypertension and the research of drug therapy target.
【作者单位】：上海交通大学生命科学技术学院力学生物学研究所;四川省泸州医学院附属医院血管外科;Department
【基金】：国家自然科学基金资助项目(31170892,11229202,11232010) 上海市青年科技启明星计划(11QA1403200)
【分类号】：R318.14

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