摘要
目的探讨肺动脉高压(PAH)大鼠肺血管重构、增殖与TMEM16A蛋白表达的关系。方法将30只8周龄雄性SD大鼠随机分为对照组、模型2周组和模型4周组,每组各10只。对照组单次腹腔注射体积分数为0.01的DMSO溶剂,模型组单次腹腔注射野百合碱50 mg/kg。应用小动物超声系统测定各组的肺加速时间(PAT)、射血时间(ET)、PAT/ET间接评估肺动脉压力,测定3组大鼠的右心室肥厚指数(RVHI),苏木精-伊红染色检测肺血管重塑等病理学指标,采用Western blot方法检测TMEM16A和PCNA蛋白的相对表达量,免疫荧光化学法检测各组肺血管平滑肌组织TMEM16A的表达。结果模型4周组PAT/ET较对照组明显降低(F=20.98,t=5.76,P<0.05)。对照组、模型2周组和模型4周组RVHI、血管横截面管壁面积与血管面积比值(WA%)和肺小动脉管壁厚度占血管直径的百分比(WT%)逐渐增高,且3组间RVHI、WT%、WA%比较差异均有统计学意义(F=166.60~234.26,t=4.37~21.03,P<0.05)。3组间TMEM16A和PCNA蛋白表达比较差异均有显著性(F=286.00、427.03,t=7.50~26.00,P<0.05)。对照组、模型2周组、模型4周组肺血管平滑肌组织TMEM16A的表达逐渐增加。3组的TMEM16A与WA%、PCNA,PCNA与WA%之间均呈正相关(r=0.901~0.969,P<0.05)。结论 TMEM16A表达水平均随造模时间延长而升高。TMEM16A表达与野百合碱诱导的PAH大鼠肺血管重构与增殖呈正相关,提示TMEM16A可能是PAH疾病进展中的重要蛋白。
Objective To study the association of TMEM16 Aprotein expression with pulmonary vascular remodeling and proliferation in rats with pulmonary artery hypertension（PAH）. Methods Thirty male Sprague-Dawley rats were randomly divided into control group,2-week model group（group A）,and 4-week model group（group B）,with 10 rats in each group.Rats in the control group received a single intraperitoneal injection of 1%（V/V）DMSO,while rats in the model groups received a single intraperitoneal injection of 50 mg/kg monocrotaline.A small animal ultrasound system was employed to determine pulmonary acce-leration time（PAT）,ejection time（ET）,and PAT/ET so as to indirectly evaluate pulmonary pressure.The right ventricular hypertrophy index（RVHI）was measured for the three groups.Pathological indices including pulmonary vascular remodeling were measured by hematoxylin and eosin staining.The relative expression levels of TMEM16 Aand PCNA proteins were measured by Western blot.Meanwhile,the expression of TMEM16 Ain the smooth muscle tissues of pulmonary vessels was measured by immunofluorescence assay for the three groups. Results Group B had significantly decreased PAT/ET values（F=20.98,t=5.76,P〈0.05）in comparison with the control group.There was a gradual increase from the control group to group A to group B in the RVHI,the ratio of the cross-sectional wall area to the cross-sectional area of blood vessels（WA%）,and the ratio of the wall thickness to the vessel diameter of pulmonary arterioles（WT%）,with significant differences in the three indices between the three groups（F=166.60-234.26,t=4.37-21.03,P〈0.05）.There were significant differences between the three groups in the expression levels of TMEM16 Aand PCNA proteins（F=286.00 and 427.03,t=7.50-26.00,P〈0.05）.There was a gradual increase from the control group to group A to group B in the expression of TMEM16 Ain the smooth muscle tissues of pulmonary vessels.There existed positive correlations of TMEM16 A with WA% and PCNA,as wel
作者
刘文源
解见业
施春英
贾秀娟
孔庆暖
章政
LIU Wenyuan;XIE Jianye;SHI Chunying;JIA Xiujuan;KONG Qingnuan;ZHANG Zheng(Department of Geriatrics, The Affiliated Hospital of Qingdao University, Qingdao 266003, Chin)
出处
《青岛大学学报（医学版）》
CAS
2018年第3期296-301,共6页
Journal of Qingdao University(Medical Sciences)
基金
青岛市科技局民生项目(16-6-2-16-nsh)
关键词
高血压
肺性
TMEM16A
肺动脉
血管重塑
细胞增殖
hypertension
pulmonary
TMEMIGA
pulmonary artery
vascular remodeling
cell proliferation
