CAJ | 학술논문

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( pulmona-ry arterial hypertension, PAH)大鼠肺组织和血浆中的表达变化。方法30只裔 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-1 MCT,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。
목적：탐토분비형족단백( secretory clusterin, sCLU)재야백합감( monocrotaline, MCT)유도폐동맥고압( pulmona-ry arterial hypertension, PAH)대서폐조직화혈장중적표체변화。방법30지예 Sprague Dawley ( SD)대서수궤분위대조조(n=6)화MCT조(n=24),MCT조급여복강주사60 mg· kg-1 MCT,대조조(n=6)주사동체적적생리염수。분별검측주사MCT후1、2、3、4주대서폐조직중sCLU적mRNA화단백질수평적표체변화、sCLU재폐혈관중적정위정황급혈장중sCLU농도적변화。결과 sCLU적mRNA화단백표체재MCT조대서폐조직중정시간의뢰성적명현승고,병차기주요정위우중구폐소동맥적포질급세포외기질중；sCLU적혈장농도수PAH적진전이축점승고,차기여폐혈류동역학지표급우실비후지수균정정상관。결론 sCLU재MCT유도PAH대서적폐조직화혈장중표체명현승고,타가능재폐혈관중구과정중발휘착중요적작용,병가능시반응PAH엄중정도적생물표지물。
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. Im-munohitochemistry 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 <br> 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 pulmo-nary vascular remodeling process. Moreover, plasma sCLU may be a potential biomarker for PAH.