大鼠高肺血流性肺动脉高压形成中肺血管结构的变化

目的探讨大鼠高肺血流性肺动脉高压形成中肺血管结构的动态变化规律.方法80只雄性SD大鼠,随机分为分流组和对照组,每组40只.分流组大鼠经腹主动脉-下腔静脉穿刺术建立高肺血流动物模型,对照组大鼠除不作穿刺术外,其余手术过程同分流组.两组分别在术后1、3 d及1、4、8周经右心插管法测量肺动脉收缩压(SPAP)、肺动脉平均压(MPAP);取心脏组织,称量右心室与左心室 室间隔重量之比RV/(LV SP)];取肺组织制作光学显微镜及电子显微镜标本,在光镜下观察肺小动脉中肌型动脉(MA)、部分肌型动脉(PMA)及非肌型动脉(NMA)构成比例及MA的相对中膜厚度(RMT)和相对中膜面积(RMA)的变化,电镜下观察肺小动脉超微结构的变化.结果与对照组比较,SPAP和MPAP在分流组术后1、3 d及4周时差异无显著性,分流术后1、8周时,SPAP、MPAP均显著高于对照组(P＜0.01);分流术后8周,RV/(LV SP)显著升高(P＜0.05);与对照组比较,分流术后1、3 d及1周时MA、PMA、NMA占肺小血管总数的百分比在两组之间差异无显著性,分流术后4、8周时大鼠MA、PMA占肺小血管总数的百分比明显增高(均P＜0.01),而NMA百分比明显降低(均P＜0.01);RMT、RMA在分流术后1、3 d及1、4周与对照组比较差异无显著性;分流术后8周时明显增高(P＜0.05).肺小动脉超微结构在分流术后3 d时仅为内皮细胞肿胀、体积增大;分流术后1周时,除内皮细胞结构改变外平滑肌细胞增大、内弹力层厚薄不均;分流术后4周时平滑肌细胞与内弹力层呈垂直生长,由收缩表型向合成表型转化;分流术后8周时细胞间见胶原纤维堆积.结论肺血管结构重建呈现明显的时间依赖性,内皮细胞肿胀出现最早,平滑肌结构改变次之,最后出现细胞外基质异常堆积.

Changes of pulmonary artery structural remodeling in pulmonary hypertension induced by high pulmonary flow in rats

To explore the changes of time-dependent pulmonary artery structural remodeling in pulmonary hypertension induced by high pulmonary flow in rats. METHODS: Eighty male SD rats were randomly divided into control group (n =40) and shunt group (n = 40). Rats in shunt group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. In the control group, rats experienced the same experimental processes except the shunting procedure. After 1 day, 3 days, 1 week, 4 weeks, and 8 weeks of experiment, systolic pulmonary artery pressure (SPAP) and mean pulmonary artery pressure (MPAP) of each rat were evaluated by using a right cardiac catheterization procedure. Heart tissues were separated as right ventricle (RV) and left ventricle plus septum (LV+SP), and the ratio of RV to LV+SP RV/ (LV+ SP)] was calculated. The morphologic changes including micro- and ultra-structural changes of pulmonary arteries of rats were observed under optical microscope and electro-microscope, respectively. The percentages of muscularized artery (MA), partial muscularized artery (PMA) and non-muscularized artery (NMA) in small pulmonary arteries and median pulmonary arteries were calculated. The changes of relative medial thickness (RMT) and relative medial area (RMA) of pulmonary arteries were examined. RESULTS: Compared with control group, SPAP and MPAP did not change on day 1, day 3, and week 4. However, in week 1 and week 8 of experiment, SPAP and MPAP increased significantly (P < 0.01). Meanwhile, in week 8 of experiment, RV/ (LV+SP) increased significantly (P < 0.05). In contrast to control group, the percentages of MA, PMA, and NMA did not change in day 1, day 3 and week 1. But in week 4 and week 8, the percentages of MA and PMA increased significantly (P < 0.01) but that of NMA decreased significantly (P < 0.01). RMT and RMA did not change in day 1, day 3, week 1 and even week 4 in shunt group as compared with those of control group, but they increased significantly in week 8 (P < 0.05). The changes of ultra-structure of pulmonary arteries included that endothelial cells became swollen and large in size on day 3, smooth muscular cells increased in size besides the change of endothelial cells in week 1, and they changed from contractile phenotype to synthetic phenotype in week 4. Collagen deposited in pulmonary arteries markedly in week 8. CONCLUSION: Pulmonary artery structural remodeling develops in a time-dependent manner. Endothelial cells of pulmonary arteries become swollen firstly, followed by the proliferation of smooth muscular cells and finally by remodeling of extra cellular matrix.