慢性阻塞性肺疾病早期急性肺损伤对血管内皮形态的影响

Effect of early acute lung injury of chronic obstructive pulmonary disease on vascular endothelium morphology

目的观察慢性阻塞性肺疾病(COPD)大鼠模型造模早期急性肺损伤(ALI)对血管内皮形态的影响。方法健康雄性Wistar大鼠48只,随机分为空白组24只,COPD模型组24只。用气管内注入脂多糖(LPS)及烟熏方法制作COPD模型。分别于第2、15、28天随机处死模型组及空白组大鼠各8只进行血管内皮形态学观察。结果与空白组比较,光学显微镜下COPD模型组造模第2天部分血管壁不光滑,周围可见散在中性粒细胞及淋巴细胞浸润,少量肺间质血管可见充血;造模第15天则出现血管扩张,形态不规则,血管平滑肌不均匀,血管间质增生;造模第28天血管平滑肌增生明显,几乎占据整个血管管壁,周围有大量炎症细胞浸润。电子显微镜下COPD模型组造模第2天肺微小动脉及毛细血管内皮细胞结构基本正常,少数线粒体出现水肿;造模第15天内皮细胞间联结断裂,基底膜不完整,细胞质内细胞器增多,线粒体肿胀,内质网扩张,部分板层体空泡化;造模第28天肺微小动脉内皮细胞细胞质内吞饮小泡增多,线粒体出现水肿或空泡变性,肺毛细血管内皮细胞肿胀,毛细血管腔内可见多形核白细胞堵塞,板层体空泡化明显,内质网扩张明显。结论 COPD形成早期已经出现肺部血管内皮的改变,提示临床上对COPD早期急性肺血管的损伤不可忽视,为更好地制订治疗方案奠定基础。

Objective To observe the effect of early acute lung injury of chronic obstructive pulmonary disease（COPD）on vascular endothelium morphology in rat models.Methods Forty-eight male Wistar rats were divided into blank group and COPD model group randomly,with 24 rats in each group.The COPD model was established by lipopolysaccharide（LPS）intratracheal injection and smudging method.Eight rats in each group were chosen randomly to be killed at the 2nd,15th and 28th day,and the change of vascular endothelium morpholog was observed.Results Compared with blank group,on the 2nd day after COPD model established,some vessel wall were not smooth under the light microscopy,neutrophils and lymphocytes were scattered around,a few pulmonary interstitium blood vessel were visible congestion;on the 15th day,the blood vessel became dilated and irregular form,vascular smooth muscle was uneven,blood vessel interstitium had hyperplasia;on the 28th day,the vascular smooth muscle proliferation almost occupied the entire vessel wall,surrounded by a large number of inflammatory cell infiltration.The result under electron microscopy showed that on the 2nd day,the structure of pulmonary arteriole and endothelial cells were almost normal,a few mitochondria appeared edema;on the 15th day,endothelial cells′ coupling between each other fractured,the basement membrane was not complete and the organelles in cytoplasm increased,mitochondria swelled,endoplasmic reticulum expanded,part of laminated body became vacuolization;on the 28th day,the endocytic vesicles in the cytoplasm of endothelial cells increased,the mitochondria had edema or vacuolar degeneration,pulmonary capillary endothelial cell swelled,the polymorphonuclear leukocyte were blocked in capillary lumen,lamellar body vacuolation and endoplasmic reticulum expanded obviously.Conclusion The lung endothelial changes have appeared in the prophase of COPD,it hints that the early acute pulmonary vascular damage in COPD can not be ignored,which can establish foundation for a better treatment.