CAJ | 학술논문

目的观察Tenascin(TN)在野百合碱诱导肺动脉高压(肺高压)大鼠右心室组织中的表达变化,探讨其在心室结构重建过程中的作用.方法72只SD大鼠随机分为模型组和对照组,野百合碱一次性皮下注射法复制肺动脉高压模型,右心导管法测定肺动脉压力并计算右室/(左室+室间隔)[RV/(LV+SP)]比值,逆转录聚合酶链反应(RT-PCR)、蛋白免疫印迹(Western blot)等方法检测TN表达变化.结果用药14d后大鼠出现右心室肥大,模型组大鼠(RV/(LV+SP)(0.282±0.0472),与对照组(0.237±0.154)相比差异有显著性(P＜0.05);第21天mPAP升高,模型组大鼠肺动脉压力(26.38±3.86)mmHg明显高于对照组(15.12±1.78)mmHg(P＜0.01);TN mRNA在对照组大鼠右心室组织中微量表达,模型组大鼠TN mRNA表达水平于用药7 d后显著升高(0.34±0.14),与对照组(0.19±0.07)比较差异有显著性(P＜0.01).模型组大鼠右心室组织中TN-C蛋白表达量明显增加.结论TN在肺动脉高压右心室组织中表达增加,可能在右心室结构重建过程中发挥重要作用.
목적관찰Tenascin(TN)재야백합감유도폐동맥고압(폐고압)대서우심실조직중적표체변화,탐토기재심실결구중건과정중적작용.방법72지SD대서수궤분위모형조화대조조,야백합감일차성피하주사법복제폐동맥고압모형,우심도관법측정폐동맥압력병계산우실/(좌실+실간격)[RV/(LV+SP)]비치,역전록취합매련반응(RT-PCR)、단백면역인적(Western blot)등방법검측TN표체변화.결과용약14d후대서출현우심실비대,모형조대서(RV/(LV+SP)(0.282±0.0472),여대조조(0.237±0.154)상비차이유현저성(P＜0.05);제21천mPAP승고,모형조대서폐동맥압력(26.38±3.86)mmHg명현고우대조조(15.12±1.78)mmHg(P＜0.01);TN mRNA재대조조대서우심실조직중미량표체,모형조대서TN mRNA표체수평우용약7 d후현저승고(0.34±0.14),여대조조(0.19±0.07)비교차이유현저성(P＜0.01).모형조대서우심실조직중TN-C단백표체량명현증가.결론TN재폐동맥고압우심실조직중표체증가,가능재우심실결구중건과정중발휘중요작용.
[Objective] Tenascin-C(TN-C), a larger extracellular matrix glycoprotein, appearing at active sites of tissue remodeling, plays important roles in tissue remodeling. In rats, injection of monocrotaline (MCT) causes pulmonary hypertension, which leads to right ventricular dysfunction. To determine the potential role of TN in the pathophysiology of right ventricule remodeling, we investigated the pattern of expression of TN-C in right ventricular of monocrotaline-treated rats. [Methods] 72 rats were randomly assigned into the control (CON) group and MCT group. MCT was delivered as a single subcutaneous injection (60 mg/kg) into male Sprague-Dawley rats weighing about 180 g. The mean pulmonary arterial pressure (mPAP) was measured by right-heart catheterization, respectively. The weight ratio of the right heart ventricle to that of left ventricle and septum weight (LV+S) [RV/(LV+S)] was measured. Sequential changes of TN-C in amount, localization were analysed by reverse transcriptase-polymerase chain reaction, western blotting. [Results] After 14 days of MCT injection, the right ventricular hypertrophy was found, RV/(LV+SP) of the MCT group (0.282±0.0472) was larger than that of the CON group (0.237±0.0154), (P ＜0.05); and mPAP rose after 21 days of MCT injection, the pressure of the MCT group (26.8±3.68) mmHg was much higher than that of the CON group (15.12±1.78) mmHg, (P＜0.01). The expression of TN mRNA in right heart ventricular tissue began to increase significantly 7 days after the injection of MCT, TN mRNA in right ventricular tissue of the MCT group (0.34±0.14) was higher than that of the CON group (0.19± 0.07), (P ＜0.01). Western blotting analysis demonstrated increases in TN-C synthetic capacity in lungs of MCT-treated rats. Correlation analysis revealed that the expression of NTN-C gene was significantly related to that of RV/(LV+S) ( correlation coefficient, r =0.994,P ＜0.001). [Conclusion] TN might be involved in the pathogenesis of right ventricular remodeling with pulmonary hypertensionand it might play an important role during the course of the right ventricular remodeling.