肺组织中内皮素1、降钙素基因相关肽的表达及其与新生儿弥漫性肺出血的关系

The expression of endothelin-1、calcitonin gene-related peptide in lung tissue and its relationship with neonatal diffuse pulmonary hemorrhage

目的 探讨肺组织中内皮素 1(ET 1)、降钙素基因相关肽 (CGRP)的表达及其与新生儿弥漫性肺出血的关系。 方法 肺出血组 4 0例 ,对照组 2 0例 (新生儿其他肺部疾病 )。两组肺组织均作HE染色及弹力纤维染色 ,ET 1及CGRP免疫组化染色。免疫组化染片中 ,细胞显棕黄色至黄色为阳性。 结果 (1)肺出血组肺泡腔内充满红细胞 ,对照组阴性。 (2 )肺出血组肺血管内皮细胞、平滑肌细胞及肺神经内分泌细胞中有ET 1阳性表达 ,对照组阴性。两组CGRP在肺神经内分泌细胞内均有阳性表达而无差异。 (3)肺出血组肺毛细血管基质弹力纤维多处断裂 ,对照组阴性。 结论 两组于急性缺氧早期 ,肺神经内分泌细胞释放少量的ET 1与CGRP ,起相互代偿作用。随着肺出血组急性缺氧加重 ,肺神经内分泌细胞释放CGRP失代偿。肺血管内皮细胞异常并持续分泌ET 1。ET 1通过旁分泌途径导致肺血管痉挛 ,肺动脉高压。在肺出血组复氧过程中 ,ET 1尚通过自分泌途径 ,生成大量氧自由基 ,导致肺血管通透性增加 ,肺血管内皮细胞坏死及毛细血管破裂 ,从而发生弥漫性肺出血。肺动脉高压可致肺毛细血管基质弹力纤维断裂而加速弥漫性肺出血的发生。

Objective To study the expression of endothelin-1 (ET-1),calitonin gene-related peptide (CGRP) in lung tissue and explore its relationship with the neonatal diffuse pulmonary hemorrhage (DPH). Methods The neonatal lung tissue samples were collected from 40 cases of DPH (group A) and 20 cases of other pulmonary disease (group B). The staining of HE and elastic fibers were taken The expression of ET-1 and CGRP were examined by immunohistochemical method in both groups. The immunohistochemical positive cells appeared from brown-yellow to yellow. Results (1)The alveoli spaces were filled by many red blood cells in group A but negative in group B. (2) There was ET-1 positive expression in the pulmonary vascular endothelial cells ( PVEC ),smooth muscle cells and pulmonary neuroendocrine cells (PNECs) in group A but not in group B. The positive expression of CGRP was also found in both groups but there was no significant difference.(3)The elastic fibers of pulmonary capillary matrix broke in many place of group A but not in group B. Conclusion At the early stage of acute hypoxia,less ET-1 and CGRP which were released by PNECs were in compensation phase in both groups.According to progress of acute hypoxia in group A ,CGRP released by PNECs only was in decompensation phase,ET-1 was released abnormally and persistently by PVEC,it led to pulmonary vascular constriction,pulmonary artery hypertension by paracrine pathway. Duration of reoxygenation in group A,oxygenic free radical was produced mostly by autocrine pathway of ET-1. It led to increased pulmonary vascular permeability,necrosis of PVEC and breakage of pulmonary capillary and resulted in DPH at last. Pulmonary artery hypertension could lead to breakage of elastic fibers in pulmonary capillary matrix and accelerate occurrance of pulmonary hemorrhage.