摘要
目的观察贝那普利对百草枯(PQ)中毒大鼠肺组织病理改变、血管紧张素转化酶(ACE)及其同源物ACE2表达的影响。方法一次性PQ 60mg.kg-1灌胃建立大鼠百草枯中毒肺纤维化模型,干预组染毒后加予贝那普利10mg/(kg.d)灌胃。于染毒后第三、七、二十一天取肺组织行HE染色和Masson染色,观察大鼠肺泡炎、肺纤维化程度;免疫组化测Ⅰ、Ⅲ型胶原;Quantitative real-time PCR检测ACE、ACE2 mRNA表达;ELISA检测肺组织AngⅡ蛋白表达。结果干预组在染毒后3d、7d肺泡炎症减轻;染毒7d后,纤维化程度积分、胶原Ⅰ、胶原Ⅲ含量低于模型组。模型组染毒后各时间点大鼠肺组织ACE mRNA及AngⅡ蛋白表达逐步上调,持续至21d;第七天后ACE2 mRNA的表达降低。干预组各时间点ACE mRNA及AngⅡ蛋白低于模型组,第七天后ACE2 mRNA表达上调。结论贝那普利可能通过降低局部ACE表达或促进ACE2合成,抑制AngⅡ生成,从而减轻百草枯中毒所致肺纤维化形成。
OBJECTIVE To investigate the effects of Benazepril on histopathologic alteration and the expression of angiotensin converting enzyme（ACE） and ACE homologue ACE2 gene in lung of paraquat poisoning rats.METHODS A rat model of pulmonary fibrosis was induced by intragastric administration with a single dose（60mg·kg-1） of paraquat（PQ）.Then intervention group was treated intragastrically with benazepril at a dose of 10mg/（kg·d）.Rats were sacrificed and lungs were harvested at different time of day 3,day 7 or day 21 following poisoning.The level of pulmonary alveolitis and fibrosis were estimated by using HE staining and Masson staining.The content of typeⅠand Ⅲ collagen in lung tissue were assessed by immunohistochemistry.The expression of ACE and ACE2 mRNA were measured by quantitative real-time PCR.AngiotensinⅡprotein was detected by ELISA.RESULTS Compared with model group,intervention group exhibited signs of less serious pulmonary alveolitis on day 3 and day 7.Similarly,intervention group brought a lower fibrosis scores as well as typeⅠand Ⅲ collagen expression on day 7 and day 21.After PQ exposure,lung ACE mRNA expression and angiotensinⅡconcentration observed in model group were gradually up-regulated at each time point and were maintained until day 21,hile ACE2 mRNA expression represented a remarkable down-regulation at day 7.Expression levels of ACE mRNA and angiotensinⅡ protein in lung tissue of intervention group were lower than those of model group at all time points,whereas ACE2 gene was up-regulated on day 7 and day 21.CONCLUSION Benazepril could alleviate paraquat-induced pulmonary fibrosis,which may be due to suppressing ACE mRNA or boosting ACE2 mRNA expression,and further inhibition of AngiotensinⅡproduction in local tissue.
出处
《海峡药学》
2012年第11期35-38,共4页
Strait Pharmaceutical Journal
基金
福建省卫生厅青年科研课题(编号:2010-1-2)
关键词
百草枯中毒
肺纤维化
贝那普利
血管紧张素转化酶
Paraquat poisoning
Pulmonary fibrosis
Benazepril
Angiotensin converting enzyme
作者简介
作者简介：王晓萍，女（1963-）。毕业于福建医科大学。职称：副主任医师。从事急诊内科及EICU。联系电话：13905019331.
通讯作者：赵燊。职称：主治医师。E-mail：jzkzhaoshen@163．com。
