低氧致大鼠凝血功能异常对肺组织结构的改变及灯盏花素对其的拮抗作用

发布时间：2018-07-29 11:42

【摘要】：目的研究不同低氧时间作用下大鼠肺组织中纤溶酶原激活物抑制物(PAI-1)、活化蛋白酶C(APC)表达量及肺组织结构的变化及灯盏花素对上述改变的影响。方法选取80只SD大鼠,将其随机分为:A(常氧对照)组、B(单纯低氧)组、C(低氧+低剂量灯盏花素)组、D(低氧+高剂量灯盏花素)组。各低氧组每天置于常压性低氧(101kPa、10%O2)环境中处理8h,低剂量及高剂量灯盏花素组分别给予腹腔注射10mg/kg体质量、40mg/kg体质量的灯盏花素。于实验第3、7、14、21d每组随机处死5只大鼠,HE染色观察肺组织病理改变,RTPCR检测转化生长因子β1(TGF-β1)、PAI-1的mRNA表达量,Western blot法检测PAI-1蛋白的表达量,ELISA法检测肺泡灌洗液(BALF)中APC蛋白的表达量。结果①HE染色提示3~21d低氧环境下肺泡间隔有不同程度增厚。3~21d,B组大鼠肺组织中TGF-β1、PAI-1的mRNA表达量及PAI-1蛋白表达量均较A组增高(P0.05),BALF中APC蛋白的表达量较A组降低(P0.05),且随着低氧时间延长,上述变化越显著。PAI-1mRNA与TGF-β1表达水平呈正相关(r=0.913,P0.05)。②与B组比较,C、D组21d时肺泡间隔增厚程度减轻,TGF-β1、PAI-1的mRNA表达量及PAI-1蛋白表达量降低(P0.05),BALF中APC蛋白的表达量增加(P0.05),且D组变化较C组明显(P0.05)。结论低氧可能造成凝血功能异常,使凝血活性增高,纤溶活性及抗凝活性降低,上调PAI-1水平及下调APC水平致肺泡间隔增厚,其机制可能与TGF-β1信号通路有关。而灯盏花素可以改善低氧所致的高凝状态,减轻肺泡间隔增厚。
[Abstract]:Objective to study the changes of plasminogen activator inhibitor (PAI-1), activated protease C (APC) (C (APC) expression and lung tissue structure in rats with different hypoxic time and the effect of breviscapine on these changes. Methods Eighty Sprague-Dawley rats were randomly divided into two groups: 1 / A (normoxic control) group (simple hypoxic group) and C (hypoxic low dose breviscapine group) group D (hypoxia high dose breviscapine group). Each hypoxia group was treated with 10 1 kPA 10 O 2 for 8 h. The low dose and high dose breviscapine groups were given intraperitoneal injection of breviscapine 40 mg / kg body weight of 10mg/kg respectively. Five rats in each group were killed at random on day 3, 7, 1421 to observe the pathological changes of lung tissue. The expression of transforming growth factor 尾 1 (TGF- 尾 1) and PAI-1 was detected by RT-PCR. The expression of PAI-1 protein was detected by Western blot method. The expression of APC protein in alveolar lavage fluid (BALF) was detected by Elisa. Results 1HE staining showed that the expression of mRNA and PAI-1 protein in lung tissue of group B was significantly higher than that of group A (P0.05) and that the expression of APC protein in alveolar septum of group B was lower than that of group A (P0.05), and the expression of TGF- 尾 1 and PAI-1 protein in group B was lower than that in group A (P0.05), and with the increase of hypoxia time, the expression of APC protein in group B was significantly higher than that in group A (P0.05), and the expression of APC protein in group B was significantly lower than that in group A (P0.05). The above changes were significantly correlated with the expression of TGF- 尾 _ 1 (r _ (0.913) P _ (0.05). 2 compared with group B, the thickening of alveolar septum reduced the expression of mRNA and PAI-1 protein in group C (P0.05), and the change of APC protein in group D was significantly higher than that in group C (P0.05). Conclusion hypoxia may cause abnormal coagulation function, increase coagulation activity, decrease fibrinolytic activity and anticoagulant activity, increase the level of PAI-1 and down-regulate the level of APC, and result in the thickening of alveolar septum, which may be related to TGF- 尾 1 signaling pathway. Breviscapine could improve the hypercoagulability induced by hypoxia and reduce the thickening of alveolar septum.
【作者单位】：四川大学华西医院呼吸内科;
【基金】：四川省科技厅攻关项目(No.0040205301469)资助
【分类号】：R563

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