高肺血流量对大鼠肺动脉压及肺动脉平滑肌细胞增殖与凋亡的影响

Effect of high pulmonary blood flow on pulmonary artery pressure and pulmonary artery smooth muscle cell proliferation and apoptosis

目的 :建立左向右分流所致肺动脉高压的大鼠模型 ,探讨高肺血流量对肺血流动力学及肺动脉平滑肌细胞增殖和凋亡的影响。方法 :采用腹主动脉 -下腔静脉分流术建立左向右分流的大鼠模型 ,观察术后 6周和 1 1周肺血流动力学 ,右心室肥厚和肺动脉舒张反应的改变。采用免疫组织化学和原位缺口末端标记方法对 1 1周组大鼠肺血管平滑肌细胞进行增殖和凋亡状态的研究。结果 :术后 6周与 1 1周大鼠肺动脉收缩压、肺动脉平均压、右心室 (RV)与左心室加室间隔 (LV +S)的比值较同龄对照组明显增加 ,而且 1 1周分流组肺动脉收缩压较 6周分流组进一步增高。在 1 1周分流组大鼠中 ,乙酰胆碱 (ACh)产生的肺动脉环舒张反应较对照组明显减弱 ,而硝普钠(SNP)产生的肺动脉环舒张百分比无明显变化。 1 1周分流组大鼠肺动脉平滑肌细胞增殖指数 (PI)、凋亡指数(AI)、PI/AI比值明显高于 1 1周对照组大鼠肺动脉平滑肌细胞。结论 :腹主动脉 -下腔静脉分流术可导致肺动脉高压形成。高肺血流量引起的内皮依赖性肺血管舒张功能失调对肺动脉高压的形成有重要的影响 ,肺动脉平滑肌细胞增殖的增加和凋亡的相对减少在肺动脉高压的发生中起重要作用。该模型简单、可靠、重复性好。

Objective: To establish a rat model of pulmonary hypertension secondary to left to right shunt and to study the effect of high blood flow on pulmonary hemodynamics and pulmonary artery smooth muscle cell proliferation and apoptosis. Methods: By producing shunt between the abdominal aorta and inferior vena cava, a left to right shunt was formed in six week and eleven week shunt groups, where pulmonary hemodynamics, the change of right ventricle hypertrophy and the relaxation of the isolated pulmonary artery rings were studied. Immunohistochemistry and TUNEL (TdT mediated dUTP biotin nick end labeling) were also used on cases of eleven week shunt group and eleven week control group to detect cell proliferative and apoptotic status. Results: Compared with control group, PASP, MPAP, RV/LV+S elevated obviously in shunt group of the same age. The PASP of eleven week shunt group elevated more obviously compared with six week shunt group. By eleven weeks of high pulmonary flow, acetylcholine(ACh) produced less relaxation than in control animals,proliferative indexes (PI), the apoptotic indexes (AI) of the pulmonary artery smooth muscle cells from the eleven week shunt group were higher than those of eleven week control group. The ratio of PI and AI was significantly higher in shunt group than that of control group. Conclusion: Dysfunction of pulmonary endothelium dependent vasorelaxation caused by high pulmonary flow was involved in the development of pulmonary hypertension. Imbalance of pulmonary artery SMC PI and AI in shunt rats also played a key role in pulmonary hypertension. Besides, this model was simple, reliable and stable.whereas sodium nitroprusside(SNP) produced almost the same relaxation in control group. And the