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山东大学学报(医学版) ›› 2014, Vol. 52 ›› Issue (10): 9-14.doi: 10.6040/j.issn.1671-7554.0.2014.313

• 基础医学 • 上一篇    下一篇

剪切力对肺微血管内皮细胞凋亡的早期生物学效应

杜庆霞1,2, 李福海1, 赵翠芬1, 孔清玉1, 黄晓阳1, 夏伟1   

  1. 1. 山东大学齐鲁医院儿科, 山东 济南 250012;
    2. 济南市儿童医院, 山东 济南 250022
  • 收稿日期:2014-05-15 修回日期:2014-09-18 出版日期:2014-10-10 发布日期:2014-10-10
  • 通讯作者: 夏伟。E-mail:cicql@163.com E-mail:cicql@163.com
  • 基金资助:
    山东省科技发展计划(2011GGH21817)

Early effect of shear stress on the apoptosis of pulmonary microvascular endothelial cells

DU Qingxia1,2, LI Fuhai1, ZHAO Cuifen1, KONG Qingyu1, HUANG Xiaoyang1, XIA Wei1   

  1. 1. Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Jinan Pediatric Hospital, Jinan 250022, Shandong, China
  • Received:2014-05-15 Revised:2014-09-18 Online:2014-10-10 Published:2014-10-10

摘要: 目的 观察剪切力对体外培养的大鼠肺微血管内皮细胞(PMVECs)凋亡的早期生物学效应及PMVECs抗凋亡相关基因BCL-2表达的变化,探讨其在高血流性肺动脉高压早期发病机制中的作用。方法 用自制的多层流动腔对体外培养的大鼠PMVECs施加剪切力作用,采用Annexin V/PI双染法检测剪切力作用不同时间PMVECs凋亡的变化;采用实时荧光定量PCR及Western blotting法分别从mRNA及蛋白水平上检测不同实验组PMVECs抗凋亡相关基因BCL-2表达的变化。结果 剪切力可引起PMVECs凋亡增加,且随着剪切力作用时间的延长,PMVECs凋亡率逐渐增加。抗凋亡相关基因BCL-2在剪切力作用0.5 h组中的相对表达量低于对照组,随着剪切力作用时间的延长,BCL-2的相对表达量逐渐增高。结论 剪切力对于PMVECs凋亡有促进作用,且能够改变抗凋亡相关基因BCL-2的表达。

关键词: 高血压, 肺性, 剪切力, 凋亡, 肺微血管内皮细胞

Abstract: Objective To observe the early effect of shear stress on the apoptosis of pulmonary microvascular endothelial cells (PMVECs) and the expression of anti-apoptotic gene BCL-2, and to elucidate the early pathogenesis of pulmonary hypertension induced by high pulmonary blood flow. Methods Self-made perfusion system was used to exert shear stress on rat PMVECs. The Annexin V/PI staining was applied to observe the apoptosis of different groups. Real-time PCR and Western blotting were performed to measure the relative expressions of BCL-2 in the mRNA and protein levels respectively. Results Flow cytometry analysis showed that the shear stress could induce the apoptosis of the PMVECs, which would increase with the extending of the acting time. The relative expression of BCL-2 in the 0.5 h group was lower than that in the control group, and the expression would increase as the acting time extended. There was significant difference between the groups. Conclusion The shear stress can promote the apoptosis of the PMVECs and alter the expression of anti-apoptotic gene BCL-2.

Key words: Shear stress, Pulmonary microvascular endothelial cells, Hypertension, pulmonary, Apoptosis

中图分类号: 

  • R725.4
[1] Duffels M G, Engelfriet P M, Berger R M, et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry[J]. Int J Cardiol, 2007, 120(2): 198-204.
[2] Dickinson M G, Bartelds B, Borgdorff M A, et al. The role of disturbed blood flow in the development of pulmonary arterial hypertension: lessons from preclinical animal models[J]. Am J Physiol Lung Cell Mol Physiol, 2013, 305(1): 1-14.
[3] Budhiraja R, Tuder R M, Hassoun P M. Endothelial dysfunction in pulmonary hypertension[J]. Circulation, 2004, 109(2): 159-165.
[4] Ando J, Yamamoto K. Vascular mechanobiology: endothelial cell responses to fluid shear stress[J]. Circ J, 2009, 73(11): 1983-1992.
[5] Sakao S, Taraseviciene-Stewart L, Lee J D, et al. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells[J]. FASEB J, 2005, 19(9): 1178-1180.
[6] Masri F A, Xu W, Comhair S A, et al. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension[J]. Am J Physiol Lung Cell Mol Physiol, 2007, 293(3): 548-554.
[7] Levy M, Maurey C, Celermajer D S, et al. Impaired apoptosis of pulmonary endothelial cells is associated with intimal proliferation and irreversibility of pulmonary hypertension in congenital heart disease[J]. J Am Coll Cardiol, 2007, 49(7): 803-810.
[8] Gallik S, Usami S, Jan K M, et al. Shear stress-induced detachment of human polymorphonuclear leukocytes from endothelial cell monolayers[J]. Biorheology, 1989, 26(4): 823-834.
[9] Teichert-Kuliszewska K, Kutryk M J, Kuliszewski M A, et al. Bone morphogenetic protein receptor-2 signaling promotes pulmonary arterial endothelial cell survival: implications for loss-of-function mutations in the pathogenesis of pulmonary hypertension[J]. Circ Res, 2006, 98(2): 209-217.
[10] Taraseviciene-Stewart L, Kasahara Y, Alger L, et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension[J]. FASEB J, 2001, 15(2): 427-438.
[11] Campbell A I, Zhao Y, Sandhu R, et al. Cell-based gene transfer of vascular endothelial growth factor attenuates monocrotaline-induced pulmonary hypertension[J]. Circulation, 2001, 104(18): 2242-2248.
[12] Zhao Y D, Campbell A I, Robb M, et al. Protective role of angiopoietin-1 in experimental pulmonary hypertension[J]. Circ Res, 2003, 92(9): 984-991.
[13] Ameshima S, Golpon H, Cool C D, et al. Peroxisome proliferator-activated receptor gamma (PPARgamma) expression is decreased in pulmonary hypertension and affects endothelial cell growth[J]. Circ Res, 2003, 92(10): 1162-1169.
[14] Ingram D A, Mead L E, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood[J]. Blood, 2004, 104(9): 2752-2760.
[15] Ingram D A, Mead L E, Moore D B, et al. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells[J]. Blood, 2005, 105(7): 2783-2786.
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