韧黏素在野百合碱诱导肺动脉高压大鼠肺组织中表达与分布

The Expression and Distribution of Tenascin in Pulmonary Hypertensive Rats Induced by Monocrotaline

目的:观察韧黏素(TN)在肺动脉高压(肺高压)大鼠肺动脉中的表达与分布,探讨其与肺高压肺血管重建的关系。方法:72只SD大鼠随机分为模型组和对照组,野百合碱1次性皮下注射法复制大鼠肺高压模型,右心导管法测平均肺动脉压力(mPAP),计算右心室(RV)/犤左心室+室间隔(LV+S)犦比值,免疫组织化学染色和RT-PCR法检测TN表达。结果:模型组大鼠第14天右心室肥大,第21天模型组大鼠mPAP升高至(26.38±3.86)mmHg与对照组(15.12±1.78)mmHg比较,差异有显著性(P<0.01);TNmRNA在对照组大鼠肺组织中微量表达,模型组大鼠TNmRNA表达水平于用药7天后显著升高(0.35±0.10),与对照组(0.19±0.07)比较差异有显著性(P<0.05)。TN仅在正常组肺动脉外膜处微量表达,模型组TN分布随着平均肺动脉压力增加而越加广泛。结论:TN可能参与肺动脉高压肺血管结构重建过程,在肺小动脉结构重建中可能发挥重要作用。

Objective:To study the expression and distruction of tenascin (T N) gene in pulmonary vascular remodeling associated with pulmonary hypertension in duced by monacrotaline. Methods:Seventy-two Sprague-Dawley rats were randomly assigned into the control (CON) group and monocrotaline(MCT) group. MCT was subc utaneously administrated by a single injection into male rats.The mean of pulmon ary arterial pressure(mPAP) was measured by right-heart catheterization, respec tively.The ratio of the right ventricle weight (RV) to left ventricle weight (LV ) plus septum weight (S) [RV/(LV+S)] were measured and calculated. RT-PCR an d immunohistochemical staining were used to detect the expression and distribution of TN. Results: After 14 days of MCT injection, the right ventricular hypertrop hy was displayed ,and mPAP elevated at 21st days after MCT injection, and the pr essure of the MCT group (26.38±3.86) mmHg was much higher than that of the CON group(15.12±1.78)mmHg, P< 0.01; the expression of TN mRNA in lung tissue began to increase significantly at 4th days after MCT injection, TN mRNA in lung tissu e of the MCT group(0.35±0.10) was higher than that of the control group (0.19± 0.07), P< 0.05. Positive staining for TN was occasionally observed in lung paren chyma from control animals. TN positive foci were first observed in the parenchy ma surrounding small muscularized pulmonary arteries in MCT-treated rats at day 4;these foci became more pronounced and frequent as the disease progressed. TN was also observed in the media of the intrapulmonary artery at day 28. Conclusio n: TN may be involved in the pathogenesis of pulmonary artery remodeling with pu lmonary hypertensive rats and itmay play an important role in the small pulmonar y artery remodeling. [