高肺血流性肺动脉高压大鼠肺间质的病理变化

Pulmonary interstitial changes in pulmonary hypertension induced by high pulmonary blood flow

目的观察腹主动脉一下腔静脉分流构建的高肺血流性肺动脉高压大鼠肺间质的变化。方法SD大鼠（180～230g）65只，采用随机数字表法分为正常组（20只）、假手术组（20只）和模型组（25只）。模型组大鼠行腹主动脉．下腔静脉分流术建立高肺血流肺动脉高压，假手术组除不行穿刺外，其余手术操作同模型组。所有大鼠在术后11周分别经右心导管测定肺动脉收缩压（sPAP）、肺动脉平均压（mPAP）；测定右心室肥厚指数（RVHI）；肺组织用HE染色，在光镜下观察肺间质的变化；应用膜片钳技术记录各组大鼠肺动脉平滑肌细胞的膜电容（Cm）。结果1．模型组大鼠sPAP、mPAP及RVHI均明显高于正常组、假手术组（F=17．293、16．259、12．878，P均〈0．01）；2．模型组大鼠的管壁面积与管总面积比（W／V）和管壁厚与管外径比（T／D）均高于正常组、假手术组（F=85．717、22．795，P均〈0．01）；3．模型组大鼠Cm高于正常组和假手术组（F=8．704，P均〈0．01）；4．mPAP与W／V、T／D及Cm呈正相关（r=0．669、0．662、0．663，P均〈0．01）。结论腹主动脉一下腔静脉构建的高血流性肺动脉高压大鼠模型出现肺动脉平滑肌细胞肥大、肺血管壁增厚、炎性细胞浸润明显的肺间质改变。

Objective To study the pulmonary interstitial changes in pulmonary hypertension induced by high pulmonary blood flow. Methods Sixty-five male or female Sprague-Dawley rats （ 180 - 230 g） were used and randomly divided into 3 groups ： normal group （ n = 20 ） ; sham group （ n = 20 ）, only exposing the abdominal aorta and inferior vena cava about 10 -20 minutes;model group（ n = 25 ） , rats in this group were subjected to an abdominal aorta-inferior vena cava shunt to create animal models of high pulmonary. After operation, all the rats were reared under the same conditions for 11 weeks. Then, the systolic pulmonary artery pressure （ sPAP ） and mean pulmonary artery pressure （mPAP） of every rat were determined by means of homemade right heart catheterization. After that, the fight ventricle （RV） was separated from the left ventricle （LV） and septum （S） ,then weighed. And fight ventricular hypertrophy index （RVHI） was measured by the ratio of RV to LV ＋ S [ RV/（ LV ＋ S） ]. In addition, the morphological changes of pulmonary interstitial of rats were observed under optical microscope by means of hematoxylin-eosin （HE） staining. In the end, single pulmonary artery smooth muscle cell （PASMC） was isolated through acute enzyme separation. Then membrane capacitance （Cm） was recorded through in the method of patch clamp technique. Results 1. Compared with sham group and normal group,the sPAP, mPAP and RVHI of model group increased significantly （F = 17. 293, 16. 259,12. 878,all P 〈 0.01 ）. 2. In contrast to sham group and normal group, arterial wall area/vessel area （W/V） and arterial wall thickness/vessel external diameter（T/D） in model group increased significantly（ F = 85. 717,22. 795, all P 〈 0.01 ）. 3. The membrane capacitance of model group was bigger than that of sham group and normal group（ F = 8. 704,P 〈 0.01 ）. 4. mPAP was positively correlated with W/V, T/D and Cm （ r = 0. 669,0. 662,0. 663, all P 〈 0. 01 ）. Conclusions Shunts from abdominal aorta-inferior vena cava in SD rats caused high pulmonary blood flow-induced pulmonary hypertension, and these rats appeared with pulmonary smooth muscle cells hypertrophy, pulmonary vascular wall thickening and inflammatory cells infiltration.