肺动脉高压时内源性血管弹性蛋白酶的动态变化与肺血管重建关系的实验研究(英文)

Relationship between elastolytic activity and-pulmonary remodeling in rats with pulmonary-hypertension induced by monocrotaline

摘要:

目的：肺动脉高压是一种以肺血管重建为主要病理改变的肺血管增生性疾病,其机制十分复杂,至今尚未完全阐明,近年来的研究表明,内源性血管弹性蛋白酶(EVE)与肺动脉高压时的肺血管病变密切相关,该研究旨在探讨肺动脉高压时EVE的动态变化及其与肺血管重建之间的关系。方法：100只成年SD大鼠随机分为正常组和模型组(均n=50)。模型组大鼠皮下注射60 mg/kg野百合碱诱导肺动脉高压。于实验第2,8,14,21天,每组各处死12只大鼠,取6只荧光分光光度计检测肺动脉的弹性蛋白离解活性,并通过右心导管法测定肺动脉压力;余下6只对周围肺动脉进行组织病理学分析。结果：肺动脉的弹性蛋白离解活性在注射野百合碱后的第2天即明显升高至(3.87±0.19)×10-8U/mg,第8天降为(0.18±0.2)×10-8U/mg,第14天再次升高至(1.45±0.18)×10-8U/mg,第21天维持在(1.91±0.18)×10-8U/mg。而肌性肺动脉的比例增加在注射野百合碱后第8天出现,肺动脉中膜的增厚及肺动脉压力的增高在第14天后出现。结论：EVE活性的早期升高可能是肺动脉高压的一种重要触发因素;EVE活性的第2次升高可能与肺高压的进展有关。

Abstract:

OBJECTIVE: Pulmonary hypertension is a proliferative vascular disease characterized by pulmonary vascular structural remodeling.Until now,the pathogenesis of pulmonary hypertension has not been fully understood. Recent many studies have suggested that endogenous vascular elastase plays a pivotal role in the vascular changes associated with pulmonary hypertension.The study aimed to explore the relationship between elastolytic activity and pulmonary remodeling in rats with pulmonary hypertension induced by monocrotaline. METHODS: One hundred mature Sprague-Dawley rats were randomly assigned into Normal and Model groups (both n=50). Rats in the Model group were induced with pulmonary hypertension by subcutaneous injection of monocrotaline (60 mg/kg). The elastolytic activity was measured by a fluorescence microplate reader and the pulmonary artery pressure was detected by catheterization at 2, 8,14 and 21 days post-injection. Light microscopic structural analysis of the peripheral pulmonary vasculature was performed at the same time points. RESULTS: The elastolytic activity increased significantly to(3.87±0.19)×10~(-8) U/mg at 2 days, and then decreased to (0.18±0.2)×10~(-8) U/mg at 8 days after injection, but on the 14th day it increased again to(1.45±(0.18)×)10~(-8) U/mg and remained high at (1.91±0.18)×10~(-8) U/mg on the 21st day.The extension of muscle into distal arteries was observed on the 8th day post-injection.Increased pulmonary artery pressure and medial wall thickness were present on the 14th day post-injection. CONCLUSIONS: The early increase in the elastolytic activity may be related to the initiation of pulmonary hypertension.The second increase may be involved in the development of this disease.