摘要
目的探讨分泌型簇蛋白(secretory clusterin,sCLU)在野百合碱(monocrotaline,MCT)诱导肺动脉高压(pulmonary arterial hypertension,PAH)大鼠肺组织和血浆中的表达变化。方法 30只♂Sprague Dawley(SD)大鼠随机分为对照组(n=6)和MCT组(n=24),MCT组给予腹腔注射60 mg·kg-1MCT,对照组(n=6)注射同体积的生理盐水。分别检测注射MCT后1、2、3、4周大鼠肺组织中sCLU的mRNA和蛋白质水平的表达变化、sCLU在肺血管中的定位情况及血浆中sCLU浓度的变化。结果 sCLU的mRNA和蛋白表达在MCT组大鼠肺组织中呈时间依赖性的明显升高,并且其主要定位于重构肺小动脉的胞质及细胞外基质中;sCLU的血浆浓度随PAH的进展而逐渐升高,且其与肺血流动力学指标及右室肥厚指数均呈正相关。结论 sCLU在MCT诱导PAH大鼠的肺组织和血浆中表达明显升高,它可能在肺血管重构过程中发挥着重要的作用,并可能是反应PAH严重程度的生物标志物。
Aim To investigate the expression pattern of secretory clusterin （ sCLU） in lung tissues and plas-ma of rats with pulmonary arterial hypertension （ PAH） induced by monocrotaline （ MCT ） . Methods Thirty male SD rats were randomly divided into control group （ n=6 ） and MCT group （ n=24 ） , and were intraper-itoneally injected 60 mg·kg-1 MCT for MCT group or equal volume normal saline for control group. Real time PCR and Western blot were performed to investi-gate the expression pattern of sCLU mRNA and protein in rat lungs 1 （ n=6 ） , 2 （ n=6 ） , 3 （ n=6 ） and 4 （n=6） weeks after MCT injection, respectively. Immunohitochemistry was performed to determine the lo-calization of sCLU in rat lungs. Enzyme linked immu-nosorbent assay was performed to detect the concentra-tion of sCLU in rat plasma. Results Expression of sCLU mRNA and protein elevated significantly in time-dependent manners in rat lungs of MCT group, and sCLU mainly localized in the cytoplasma and extracel-lular matrix of cells in pulmonary arterioles. Further-more, sCLU plasma levels were significantly elevated with the progression of PAH and had positive correla-tions with pulmonary hemodynamic indices and right ventricular hypertrophic index. Conclusion sCLU was significantly elevated in MCT induced PAH rat lungs and plasma, and it may participate in the pulmonary vascular remodeling process. Moreover, plasma sCLU may be a potential biomarker for PAH.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2014年第6期764-768,共5页
Chinese Pharmacological Bulletin
基金
国家重点基础研究发展计划(973计划)资助项目(No 2010CB529505)
首都医科大学附属北京朝阳医院青年基金(No YQ201317)
关键词
分泌型簇蛋白
肺动脉高压
肺血管重构
野百合碱
大鼠
增殖
secretory clusterin
pulmonary arterial hypertension
pulmonary vascular remodeling
mono-crotaline
rat
proliferation
