摘要
目的探讨肿瘤坏死因子-α(TNF-α)在体-肺分流性肺动脉高压大鼠肺组织和血浆中的表达变化。方法 40只雄性SD大鼠随机分为假手术组(n=10)和手术模型组(n=30)。术后8周和12周右心导管法评估各组大鼠肺血流动力学变化,计算右心室肥厚指数并检测肺组织中TNF-α的mRNA表达变化、血浆中TNF-α浓度的变化及肺血管重构情况。结果手术组大鼠TNF-α的血浆浓度随肺动脉高压的严重程度而逐渐升高,且其与肺血流动力学指标及右室肥厚指数均呈正相关[RVSP(r=0.7666,P<0.01),PASP(r=0.7667,P<0.01),mPAP(r=0.7424,P<0.01)及RVHI(r=0.6846,P<0.01)]。TNF-α的mRNA表达在术后8周[(1.60±0.52)倍]和12周[(2.29±0.60)倍]较假手术组均显著升高(均P<0.01),且呈时间依赖性,同时手术组大鼠肺血管呈现明显的病理重构。结论 TNF-α在先天性体-肺分流性肺动脉高压大鼠的血浆和肺组织中表达显著升高,其可能在肺血管重构发生发展过程中发挥着重要作用,并可能是反映先天性体-肺分流性肺动脉高压严重程度的生物标志物。
Objective To investigate the expression differences of TNF-αin lung tissues and plasma of rats with pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunt.Methods Forty male SD rats were randomly divided into sham operated group（n=10）and operated model group（n=30）.After 8 and 12 weeks operation,hemodynamic parameter was measured and recorded through the right-heart catheterization,the right ventricular hypertrophic index calculated,and real-time PCR was performed to investigate the expression changes of TNF-αmRNA in rat lungs.At the same time,enzyme linked immunosorbent assay（ELISA）was performed to detect the concentration of TNF-αin rat plasma.Results TNF-αplasma levels were significantly elevated with the progression of pulmonary arterial hypertension and had positive correlations with pulmonary hemodynamic index and right ventricular hypertrophic index[RVSP（r=0.7666,P0.01）,PASP（r=0.7667,P0.01）,mPAP（r=0.7424,P0.01）and RVHI（r=0.6846,P0.01）].Expression of TNF-αmRNA elevated significantly at 8 weeks（1.60±0.52）and 12 weeks（2.29±0.60）after operation in time-dependent manners as compared with the sham operated group,and furthermore,the pulmonary vascular remodeling in the operated group was obvious.Conclusion TNF-αwas significantly elevated in plasma and lungs of rat with pulmonary arterial hypertension,and it may participate in the pulmonary vascular remodeling process.Moreover,plasma TNF-αmay be a potential biomarker for pulmonary arterial hypertension.
作者
张俊志
李涵葳
张中军
何婷
Zhang Junzhi;Li Hanwei;Zhang Zhongjun(Department of Anesthesiology,The 2nd Clinical Medicine College（Shenzhen People ＇s Hospital）of Jinan University,Shenzhen 518020,China)
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2018年第4期445-449,共5页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
国家自然科学基金(青年基金)资助项目(No.81700435)
湖北省卫生计生委科研项目(No.WJ2015MB148)
深圳市科技创新项目(No.JCYJ20150403102020225)
关键词
肿瘤坏死因子-Α
肺血管重构
体-肺分流性肺动脉高压
TNF -α
pulmonary vascular remodeling~ systemic to pulmonary associated pulmonary arterial hypertension
