血管紧张素Ⅱ在大鼠全氟异丁烯急性吸入性肺损伤中的作用初探

Role of angiotensinⅡin perfluoroisobutylene-induced acute lung injury in rats

目的初步探讨血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)在大鼠全氟异丁烯(PFIB)急性吸入性肺损伤中的作用。方法 28只雄性Wistar大鼠,随机分为空白对照组(0 h)和PFIB染毒后1、2、4、8、16和24 h活杀组(n=4)。其中PFIB染毒组头部暴露动态吸入PFIB染毒(剂量为145 mg/m3×8 min),空白对照组于过滤空气暴露8min。分别在染毒后相应时间点收集大鼠肺组织、血浆和支气管肺泡灌洗液(brochoalveolar lavage fluid,BALF)等样本,测定肺湿/干重比(W/D)、BALF蛋白含量,并进行肺组织病理学检查;同时测定肺组织匀浆与血浆中AngⅡ含量及肺组织匀浆血管紧张素转换酶(angiotensin converting enzyme,ACE)活性。结果大鼠PFIB染毒后16 h肺W/D和BALF中蛋白含量显著升高,发生急性肺间质与肺泡水肿,伴大量多形核白细胞渗出,染毒后24 h肺损伤程度明显缓解。肺组织AngⅡ含量在染毒后8 h前各时点呈现升高的趋势,但无统计学意义,染毒后16 h与24 h则显著低于空白对照组;血浆中AngⅡ含量与肺组织ACE酶活性在染毒后各时点呈现一定程度的波动,但与对照组比较均无显著性差异。结论大鼠吸入PFIB中毒后肺组织ACE活性及AngⅡ含量与肺损伤程度未见明显关联,其病理学意义有待进一步探讨。

Objective To investigate tentatively the role of angiotensionⅡ（ AngⅡ） in perfluoroisobutylene （ PFIB）-in-duced acute lung injury （ ALI） in rats.Methods Twenty-eight male Wistar rats were randomly divided into one control group（0 h） and six PFIB-exposed groups which were executed at 1, 2, 4, 8, 16 and 24 h after PFIB exposure （n=4）. The PFIB-exposed groups inhaled PFIB at a concentration of 145 mg/m3 for 8 min in a flow-past header while the control group was exposed to the filtered air in a similar manner .After execution at the corresponding time-point, the samples of the lung, serum and brochoalveolar lavage fluid （BALF） were harvested.The measurement of the lung wet-to-dry weight ratio （ W/D） and total protein content in BALF , and the histopathological examination of the lung were carried out to evalu -ate the degree of lung injury .The over-time changes in the content of AngⅡin the lung homogenates and blood plasma and the activity of angiotensin converting enzyme （ ACE） in the lung tissue were observed .Results The lung W/D and total protein content in BALF were increased significantly at 16 h after PFIB exposure with severe acute lung edema and abun-dant neutrophil exudation to the alveoli , which were alleviated dramatically at 24 h after PFIB exposure .The content of AngⅡin the lung homogenate showed a tendency of increase during the first 8 hours with significant decrease at 16 and 24 h after exposure.However, the content of AngⅡin the plasma and the activity of ACE in the lung experienced of fluctuations , but without significant difference compared to the control group .Conclusion There is no obvious correlation between the extent of lung injury and that of AngⅡin the lung.The pathological significance of AngⅡin PFIB-induced ALI needs to be further clarified.