目的:探讨血管内皮生长因子(VEGF)在低氧性肺动脉高压形成中的意义及多黏菌素B(PMB)对其的影响。方法:将30只SD大鼠分成正常对照组(N组)、低O2高CO24w组(F组)、低O2高CO24w+PMB组(P组),观察各组大鼠肺动脉平均压(InPAP)、右心室重量比(RV/LV+S)、肺小动脉管壁面积/管总面积(WA/TA)、中膜厚度(PAMT)及超微结构,用ELISA法检测血清和肺组织VEGF含量,免疫组化法检测肺组织VEGF、蛋白激酶C(PKC)表达的变化。结果:①F组大鼠mPAP、RV/LV+S、血清和肺组织VEGF的含量明显高于N组(P〈0.01),P组则低于F组(P〈0.01)。②病理显示F组WA/TA、PAMT较N组增高(P〈3.01),内弹力板扭曲明显,胶原纤维增多,中膜平滑肌细胞增生。P组大鼠血管壁的改变明显减轻。③F组大鼠肺细小动脉VEGF蛋白及PKC的表达与N组比较明显增加(P〈0.01),而P组与F组比较,则明显降低(P〈0.05,〈0.01)。结论:低氧诱导肺动脉VEGF的增加,后者参与了慢性低氧性肺动脉高压的形成,PKC可能是低氧时上调VEGF表达的重要因素。
To explore the roles of vascular endothelial growth factor (VEGF) in hypoxia pulmonary hypertension and effect of Polymyxin B(PMB). Methods: Thirty SD rats were randomly divided into normal control group (N), hypoxia hypercapnia group(F), hypoxia hypercapnia +PMB group (P). The levels of VEGF in serum and in lung tissue were measured with ELISA; the pathology of pulmonary arterioles was observed under light microscopy, electron microscopy and image analysor; the expression of VEGF,PKC were observed by immunohistochemistry. Results:①Mean pulmonary arterial pressure(mPAP), weight ratio of RV to LV+S, the leves of VEGF in serum and in lung tissue of group F were significantly higher than those of group N and group P (P〈0.01).②Pathological changes showed that vessel wall area/total area(WA/TA), thickness of tunica media of pulmonary arterioles (PAMT)were much higher in rats of group F than those of group N and group P (P〈0.01); proliferation of smooth muscle cells and collagenous fibers of pulmonary arterioles in rats of group F and PMB could reverse the changes mentioned above.③VEGF and PKC in pulmonary arterioles were significantly higher in rats of group F than that of group N(p〈0.01), they were significantly decreased in rats of group P than that of group F (p〈0.05,〈0.01). Conclusion: Hypoxia strongly stimulates the production of VEGF in pulmonary arterial vascular,which plays an important role in the process of hypoxia pulmonary hypertension, and hypoxia-induced PKC activation is one kind of basic mechanisms in this course.