β-抑制蛋白1促进缺氧性肺动脉高压的肺血管胶原合成作用探讨  

Effects of β-arrestin 1 on promoting synthesis of pulmonary artery collagen in pulmonary hypertension induced by hypoxia

作　　者：周雪[1] 马晶茹[1] ZHOU Xue MA Jingru(Department of Cardiovascular Medicine, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, Liaoning Province, China)

机构地区：[1]沈阳医学院附属第二医院心血管内科,辽宁沈阳110035

出　　处：《解放军医学院学报》2016年第11期1173-1176,1182,共5页Academic Journal of Chinese PLA Medical School

摘　　要：目的探讨β-抑制蛋白1(β-arrestin1)对肺动脉高压(pulmonary artery hypertension,PAH)肺血管胶原合成的影响,进一步明确PAH肺血管重构的分子机制。方法 20只雄性SD大鼠随机分为对照组(n=10)和低氧组(n=10),低氧组大鼠置于低氧舱内(氧浓度100 ml/L)3周,正常对照组动物饲养于常氧动物笼内;右心导管法测定肺动脉平均压(mean pulmonary arterial pressure,m PAP),检测右心室与左心室+室间隔比值[RV/(LV+S)];免疫组织化学和Western blot方法检测肺动脉中胶原Ⅰ(CollagenⅠ)和β-arrestin 1的表达;沉默β-arrestin 1基因,采用Western blot和免疫荧光方法检测低氧环境下肺动脉血管平滑肌细胞(pulmonary arterial smooth muscle cells,PASMCs)中CollagenⅠ的表达。结果与常氧组相比,低氧处理组大鼠m PAP[(31.35±1.35)mm Hg](1 mm Hg=0.133 k Pa)以及RV/(LV+S)(30.81%±0.81%)明显升高(P<0.01),肺血管组织β-arrestin 1以及CollagenⅠ的表达水平明显增高;缺氧能够上调PASMCs中β-arrestin 1和CollagenⅠ的表达,沉默β-arrestin 1基因能够抑制缺氧诱导PASMCs胶原合成的作用。结论β-arrestin 1促进缺氧条件下肺血管胶原的合成,促进肺血管的重构,最终导致PAH的形成。Objective To investigate the roles of β-arrestin 1 in the collagen synthesis of pulmonary vessels in the pathogenesis of pulmonary hypertension induced by hypoxia, and illustrate the molecular mechanism of pulmonary vascular remodeling in pulmonary artery hypertension（PAH）. Methods Twenty male Sprague-Dawley rats were randomly divided into control group and hypoxia group, with 10 rats in each group. Rats in hypoxia group were raised in a low oxygen chamber（oxygen concentration of 100 ml/L） for 3 weeks, while rats in normal control group were raised in the normal oxygen environment. Right cardiac catheterization procedure was used to detect mean pulmonary arterial pressure（m PAP）, and the ratio of right ventricular mass to left ventricular plus septal mass [RV/LV＋S] was measured. Expressions of CollagenⅠand β-arrestin 1 in pulmonary vessel tissues were detected by immunohistochemistry assay and Western blot, while expressions of β-arrestin 1 and CollagenⅠin hypoxia-stimulated PASMCs were detected by Western blot and immunofluorence method after silencing the β-arrestin 1 gene. Results Compared with normoxic group, the m PAP（31.35±1.35 mm Hg） and RV/（LV＋S）（30.81%±0.81%） of rats in hypoxic group increased significantly（P〈0.01）, and expression of β-arrestin1 and CollagenⅠin pulmonary vascular tissues of rats raised in low oxygen condition also increased significantly. Hypoxia could upregulate the protein expression of β-arrestin1 and CollagenⅠin PASMCs, and the collagen synthesis in PASMCs induced by hypoxia was inhibited by knockdown of β-arrestin 1. Conclusion β-arrestin 1 promotes the collagen synthesis of pulmonary vessels in PAH induced by hypoxia and pulmonary vascular remodeling, thus resulting in the development of PAH.

关 键 词：β-抑制蛋白1 肺动脉高压 缺氧 胶原Ⅰ 

分 类 号：R544.16[医药卫生—心血管疾病]