整合素连接激酶在低氧诱导肺动脉高压发病机制中的作用

发布时间：2018-04-17 18:54

本文选题：整合素连接激酶 + 高血压　；参考：《临床心血管病杂志》2017年02期

【摘要】：目的:通过了解整合素连接激酶(ILK)及心肌素(myocardin)在低氧性肺动脉高压(PAH)大鼠肺组织及肺血管中的表达,探讨ILK在低氧性肺动脉高压发病机制中的作用。方法:48只SD大鼠按随机数字表法分为常氧对照组和低氧1周、2周、4周组,低氧干预大鼠置于低氧仓内,氧浓度控制在(10.5±0.5)%,每日间断低氧8h(8:00~16:00)。测定各组大鼠肺动脉平均压(mPAP)、计算右室肥厚指数[右室/(左室+室间隔),RV/(LV+S)]、管壁厚度占血管外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%);采用髓鞘碱性蛋白为底物通过液体闪烁仪测定ILK活性;实时定量PCR法测定肺动脉内ILK、糖原合成激酶3β(GSK-3β)及myocardin mRNA相对表达量;Western印迹法检测肺动脉及培养的肺动脉平滑肌细胞(PASMC)胞质内ILK、GSK-3β及myocardin蛋白相对表达量。结果:低氧2周组mPAP、右室肥厚指数、WT%、WA%均显著高于常氧对照组(均P0.05),低氧4周组差异更为显著。低氧1周组肺动脉内ILK活性即明显下降达36%(P0.05),低氧2周、4周组ILK活性均较常氧对照组明显降低(均P0.05)。低氧4周组ILK mRNA和蛋白相对表达量均显著低于常氧对照组(均P0.05),myocardin mRNA和蛋白表达变化与ILK相似(均P0.05),而GSK-3β的mRNA和蛋白表达量则呈相反趋势,显著高于常氧对照组(均P0.05)。低氧培养PASMC 24h后ILK及myocardin蛋白表达明显低于常氧对照组,而GSK-3β蛋白水平则呈相反趋势,低氧可促进其表达增加(均P0.05)。结论:慢性低氧引起ILK活性和表达下调,使其下游靶点GSK-3β表达上调,进而降低myocardin表达水平,可能是导致PAH形成的重要机制。
[Abstract]:Aim: to investigate the expression of integrin linked kinase (ILK) and cardiomyocardinin in lung tissues and pulmonary vessels of rats with hypoxic pulmonary hypertension (hypoxic pulmonary hypertension) and to explore the role of ILK in the pathogenesis of hypoxic pulmonary hypertension.Methods Forty-eight Sprague-Dawley rats were randomly divided into normoxic control group and hypoxic control group. Hypoxic intervention rats were placed in a hypoxic chamber with oxygen concentration controlled at 10.5 卤0.5. The rats were exposed to hypoxia for 8 hours a day.The mean pressure of pulmonary artery in each group was measured, and the right ventricular hypertrophy index (RV / LV S), the wall thickness as a percentage of the external diameter of the vessel and the area of the wall as a percentage of the total area of the vessel were calculated, and the myelin basic egg was used to calculate the right ventricular hypertrophy index (RV / LV S), the wall thickness as a percentage of the external diameter of the vessel and the area of the vessel wall as a percentage of the total area of the vessel.The activity of ILK was determined by liquid scintillation instrument.The relative expression of ILK, glycogen synthesis kinase 3 尾 -GSK-3 尾 and myocardin mRNA in pulmonary artery and in cultured pulmonary artery smooth muscle cells (PASMC) was measured by real-time quantitative PCR. The relative expression of ILK- GSK-3 尾 and myocardin protein in the cytoplasm of pulmonary artery and cultured pulmonary artery smooth muscle cells was detected by Western blot.Results: the mPAPand WA% of right ventricular hypertrophy in hypoxia 2 weeks group were significantly higher than those in normoxic control group (P 0.05), and the difference was more significant in hypoxia 4 weeks group.The activity of ILK in pulmonary artery of hypoxic group decreased significantly to 36% P0.05, and the activity of ILK in hypoxic group for 2 weeks and 4 weeks was significantly lower than that in normal control group (P0.05%, all P0. 05%, P 0. 05%, P 0. 05%, P 0. 05%).The relative expression of ILK mRNA and protein in hypoxia group was significantly lower than that in normoxic control group (P 0.05). The expression of myocardin mRNA and protein was similar to that of ILK (P 0.05), but the expression of mRNA and protein of GSK-3 尾 was significantly higher than that of normoxic control group (P 0.05).The expression of ILK and myocardin protein was significantly lower than that of normoxic control group after 24 hours of hypoxia culture, while the level of GSK-3 尾 protein showed a reverse trend. Hypoxia could promote the expression of ILK and myocardin protein (all P 0.05).Conclusion: chronic hypoxia induces down-regulation of ILK activity and expression, up-regulates the expression of GSK-3 尾 and reduces the level of myocardin expression, which may be an important mechanism leading to the formation of PAH.
【作者单位】：东南大学附属中大医院心内科;
【分类号】：R544.1

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