新生乳猪缺氧性肺动脉高压中平滑肌细胞增殖和凋亡

目的：研究平滑肌细胞增殖和凋亡在新生乳猪生后正常发育及缺氧性肺动脉高压肺血管重构中的作用。方法：42只新生乳猪分成正常发育组和缺氧性肺动脉高压组，其中20只新生乳猪置于低气压仓（50．8kPa)中3或11d形成不同程度的缺氧性肺动脉高压模型。采用免疫组化方法和TUNEL方法检测和观察肺小阻力动脉中层平滑肌细胞（SMC）的增殖和凋亡变化。结果：平滑肌细胞复制率在出生时即较高，出生后早期进一步升高。短期缺氧对平滑肌细胞复制率有一定程度的抑制。较长期缺氧（11d)引起肺血管重构显著变化同时，平滑肌细胞复制率显著增加；新生期无论在正常状态，缺氧或缺氧恢复阶段，在肺血管壁上均未见细胞凋亡阳性信号。结论：新生乳猪出生后肺血管重构与平滑肌细胞增殖有关。平滑肌细胞增殖在严重缺氧性肺动脉高压形成中起重要作用。细胞凋亡在出生早期肺血管重构中作用尚待研究。

Proliferation and apoptosis of lung smooth muscular cells in hypoxic pulmonary hypertension in neonatal pigs]

OBJECTIVE: To study the effects of the proliferation and apoptosis of smooth muscular cells (SMC) in small pulmonary arteries on the pulmonary vascular remodeling in hypoxia-induced pulmonary hypertensive neonatal pigs. METHODS: Forty-two pigs aged from the birthday to 14 days were divided into the normal developmental group and hypoxic hypertensive group. Twenty of them were exposed to hypobaric hypoxia (50.8 kPa) for 3 or 11 days to establish a pulmonary hypertension model. The proliferation and apoptosis of SMC in the pulmonary small arteries were studied with the immunohistochemiscal method and terminal transferase-mediated nick-end labeling (TUNEL) method. RESULTS: SMC replication rates were high (5%) at birth, and followed by a burst of replication during the early period after birth. The shorter period hypoxia did not cause the increase of SMC proliferation; and the longer hypoxia induced the pulmonary vascular wall remodeling with apparent SMC proliferation. No signal of cell apoptosis in the pulmonary vascular wall was found during the neonatal period under either the normal condition or the hypoxic condition. CONCLUSION: The pulmonary resistant vascular remodeling after birth is related to SMC proliferation and SMC proliferation plays a crucial role in the formation of severe pulmonary hypertension induced by hypoxia. The role of apoptosis in the pulmonary vascular remodeling needs further research.