卡托普利对大鼠左向右分流模型肺小动脉重构的影响

目的观察血管紧张素转换酶抑制剂（ACEI）对肺循环容量负荷过重导致的肺血管重构的影响。方法采用腹主动脉一下腔静脉瘘制造大鼠容量负荷性肺动脉高压（PH）模型，并应用卡托普利进行干预，6周后观察各组肺动脉收缩压（PASP）、舒张压（PADP）、右室收缩压（RVSP）变化；心室重量变化；采用免疫组化染色比较肺血管平滑肌细胞（VSMC）α-平滑肌肌动蛋白（α-actin）及增殖细胞核抗原（PCNA）的阳性表达，比较15-50μm无肌性动脉肌性化程度以及肺小动脉50～100μm和101150μm血管厚度与血管外径之比（％WT）。结果手术组动物RVSP、PASP、PADP较对照组显著升高（P〈0．05），手术＋卡托普利组RVSP、PASP、PADP均低于手术组（P〈0．05）；手术组RV／（LV＋S）、RV／BW、（LV＋S）／BW较对照组显著增加（P〈0．001），而手术＋卡托普利组则较手术组明显降低（p〈0．01），同对照组比较，手术组α-actin染色IOD值显著降低（P〈0．01），而手术＋卡托普利组IOD值则高于手术组（P〈0．05），手术组细胞PCNA阳性率显著升高（P〈0．01），而手术＋卡托普利组低于手术组（P〈0．05）；手术组同其他两组比较，50～100μm、101～150μm血管％WT及15～50μm血管肌性化百分比显著增加（P〈0．01，）。结论卡托普利能有效地抑制肺动脉VSMC由收缩表型向合成表型转化，抑制VSMC的增生和肥厚，防止无肌性肺小动脉的肌性化，减缓PH肺血管重构进程，提示ACEI对左向右分流型先心病肺动脉高压有治疗前景。

Effect of Captopril on Pulmonary Vascular Remodeling Induced by Left-to-right Shunt in Rats

OBJECTIVE: To investigate the therapeutic effect of angiotensin converting enzyme inhibitor on pulmonary vascular remodeling of pulmonary hypertension induced by high pulmonary blood flow. METHODS: An arterial-venous shunt was surgically created between abdominal aorta and inferior vena cava in the rat of all groups except the control group. Captopril was given to all of the rats. Six weeks after the operation,pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP) and right ventricular systolic pressure (RVSP) were measured. The rats' hearts were weighted to calculate the ratio of right ventricle mass to left ventricle plus septum mass. Immunohistochemical stains were used to identify alpha-actin and PCNA distribution in pulmonary arteries. Morphometric parameters (vascular wall thickness and muscularization) were used to assess the remodeling of small pulmonary arteries. RESULTS: The PASP, PADP, RVSP, RV/(LV+S), RV/BW, and (LV + S)/BW of the rats in the shunt group were significantly greater than those of the control group. Muscularization of small pulmonary arteries and pulmonary artery medial hypertrophy (wall thickness) were evident in the shunt group. The proliferation index of the smooth muscle cells of the small and medium-sized pulmonary arteries was significantly higher and the alpha-actin IOD was significantly lower in the rats of the shunt group than those of the control. By contrast, the levels of PASP, PADP, RVSP, RV/(LV+S), RV/BW, (LV+ S)/BW, and muscularization were lower in the rats of captopril group than those of the control. CONCLUSIONS: Captopril slows down pulmonary hypertension and remodeling development. Captopril and losartan may have preventive and therapeutic effects on pulmonary hypertension induced by congenital left-to-right shunts.