肺动脉平滑肌细胞凋亡在大鼠低氧性肺动脉重构自然逆转中的作用及分子机制

发布时间：2018-05-11 17:56

本文选题：低氧性肺动脉高压 + 自噬　；参考：《中国病理生理杂志》2017年04期

【摘要】：目的:研究肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells,PASMCs)凋亡在低氧性肺动脉重构自然逆转中的作用,并探讨其可能机制。方法:24只SD大鼠随机均分为常氧4周组、低氧4周组、低氧4周后复氧1周组及复氧6周组。分别检测右室收缩压(right ventricular systolic pressure,RVSP)、肺动脉中膜厚度(medial thickness,MT)和中膜面积(medial area,MA),以及肺动脉中膜自噬、凋亡等在低氧-复氧中的变化。大鼠原代PASMCs分为常氧48 h组、低氧48 h组、低氧48 h后复氧24 h组及常氧72 h组,观察PASMCs凋亡和自噬在低氧-复氧中的变化。再将PASMCs分为常氧72 h组、低氧48 h后复氧24 h组及低氧48 h+氯喹(自噬抑制剂)干预后复氧24 h组,观察PASMCs低氧阶段的自噬对其复氧阶段凋亡的影响。结果:(1)低氧使大鼠RVSP、右室肥厚指数、MT及MA显著升高(P0.05);复氧后上述指标逐渐降低。(2)低氧使肺动脉中膜LC3表达升高,P62表达降低,复氧后上述分子的表达逐步恢复正常。低氧显著降低了中膜cleaved caspase-3的表达,复氧1周其表达显著高于低氧组。(3)低氧期原代PASMCs cleaved caspase-3/PARP的表达显著低于常氧组,复氧后其表达明显升高(P0.05);PASMCs LC3和P62的表达在低氧期显著降低(P0.05)。(4)抑制了PASMCs低氧阶段的自噬后,其复氧阶段cleaved caspase-3/PARP表达显著降低(P0.05)。结论:PASMCs的凋亡参与了低氧性肺动脉重构的自然逆转;复氧期PASMCs凋亡的发生可能与其低氧期的自噬有关。
[Abstract]:Aim: to investigate the role of pulmonary arterial smooth muscle cells (PASMCs) apoptosis in the spontaneous reversal of hypoxic pulmonary artery remodeling and its possible mechanism. Methods Twenty four Sprague-Dawley rats were randomly divided into four groups: normoxic 4-week group, hypoxic 4-week group, 1-week reoxygenation group and 6-week reoxygenation group. The right ventricular systolic pressure of right ventricular systolic pressure (RVSPN), the thickness of pulmonary artery medial thicknessnessma (MTM) and the area of medial membrane (MCA), as well as the changes of membrane autophagy and apoptosis in pulmonary artery in hypoxic-reoxygenation were detected. The primary PASMCs of rats were divided into normoxic 48 h group, hypoxia 48 h group, reoxygenation group 24 h after hypoxia 48 h and normoxic 72 h group. The changes of PASMCs apoptosis and autophagy in hypoxic-reoxygenation were observed. Then PASMCs was divided into normoxic 72 h group, hypoxia 48 h reoxygenation 24 h group and hypoxia 48 h chloroquine (autophage inhibitor) intervention after 24 h reoxygenation group. The effect of autophagy during PASMCs hypoxia on apoptosis in reoxygenation stage was observed. Results 1) hypoxia increased RVSP, right ventricular hypertrophy index (RVSP), and decreased the expression of LC3 in pulmonary artery after reoxygenation. Hypoxia significantly decreased the expression of cleaved caspase-3, which was significantly higher than that in hypoxic group at 1 week. The expression of primary PASMCs cleaved caspase-3/PARP in hypoxia group was significantly lower than that in normoxic group. After reoxygenation, the expression of PASMCs LC3 and P62 decreased significantly in hypoxia stage. Conclusion the apoptosis of PASMCs is involved in the natural reversal of hypoxic pulmonary artery remodeling, and the apoptosis of PASMCs during reoxygenation may be related to its autophagy in hypoxic phase.
【作者单位】：第四军医大学病理学与病理生理学教研室;
【基金】：国家自然科学基金资助项目(No.81471816;No.81270328)
【分类号】：R544.1

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