全反式维甲酸对肺气肿模型大鼠的干预作用

Effects of all-trans-retinoic acid on emphysema model in rats

目的研究不同时间段给予全反式维甲酸(ATRA)对肺气肿模型大鼠的干预作用及其机制。方法60只SD大鼠随机分为6组:生理盐水组(N组)、模型组(P组)、棉籽油组(C组)、早期干预组(R1组)、中期干预组(R2组)和后期干预组(R3组),每组10只。N组大鼠气管滴注生理盐水1mL·kg-1,其余5组气管滴注5%木瓜蛋白酶1mL·kg-1建立肺气肿模型。R1、R2和R3组分别于造模后15～30d、30～45d和45～60d给予ATRA500μg·kg-1腹腔注射,C组给予棉籽油腹腔注射。观察各组支气管肺泡灌洗液(BALF)中血管内皮生长因子(VEGF)含量和细胞数,肺组织病理学改变及肺组织血管内皮生长因子受体2(VEGFR-2)、基质金属蛋白酶1(MMP-1)的表达水平。结果与N组比较,P组BALF中细胞总数明显升高(P<0.01),其中以巨噬细胞和中性粒细胞为主。R1、R2和R3组与P组比较细胞总数降低(P<0.01),此3组之间无显著差异。与N组比较,其余5组平均肺泡面积和内衬间隔增大,每个视野内肺泡数减少(P<0.01);与P组相比,R1、R2和R3组肺泡数增加、平均肺泡面积减小(P<0.01),以R1组最为明显。与N组相比,P组VEGF和VEGFR-2表达降低,MMP-1表达增高(P<0.01);与P组相比,R1、R2和R3组VEGF和VEGFR-2表达增高,MMP-1表达降低(P<0.05),R1、R2和R3组之间无显著差异。结论ATRA可以促进肺泡再生,早期干预效果较佳,这种作用可能与调节VEGF、VEGFR-2、MMP-1有关。

AIM To different time periods and weight from 180 to 220 g, study the effects of all-trans-retinoid acid its intervention mechanism. METHODS were randomized into 6 groups （n = 10）, （ATRA） on emphysema model in rats at Sixty male Sprague-Dawley （SD） rats, control group （N）, model group （P）, early intervention group （R1）, mid-intervention group （R2）, late intervention group （R3）, and cottonseed oil group （C）. Rats emphysema models were established by a single intratraeheal instillation of 5% papain 1 mL.kgq, while rats in the group N were treated by intratraeheal instillation of normal saline 1 mL· kg-1 Rats in the groups RI, R2 and R3 were given intraperitoneally with ATRA 500 μg·kg-1 at different time periods, respectively. Rats in the group C were given intraperitoneally with cottonseed oil. Rats in the group N and P were infused with normal saline and papain respectively, and then were fed for 60 days. The morphological changes of lung tissues, the expressions of vascular endothelial growth factor （VEGF） , VEGF receptor 2 （VEGFR-2） and matrix metalloproteinases 1 （MMP-1） , and bronchoalveolar lavage fluid （BALF） inflam-matory cells were measured. RESULTS Compared with the group N, the total number of BALF cells, mainly neutrophils and macrophages, increased significantly in the group P （p 〈 0.01 ）. Compared with the group P, the total number of BALF cells decreased significantly in the group RI, R2 and R3 （P 〈 0.01 ） , but there was no significant difference among the three groups. Compared with the group N, mean alveolar area and mean linear intercept increased, and the number of alveoli decreased in the other groups （p 〈 0.01）. Compared with the group p, the number of alveoli increased and mean alveolar area decreased in the group Rz, R2 and R3 （P 〈 0.01）. Compared with the group R2 and Rs, the number of alveolar increased and mean alveolar area decreased significantly in the group R1. Compared with the group N, the expression of VEGF and VEGFR-2 decreased and MMP-1 increased significantly in the group P （p 〈 0.01 ）. Compared with the group P, the expressions of VEGF and VEGFR-2 increased and MMP-1 decreased significantly in the group Rl, R2 and R3 （P 〈 0.05）, and there was no significant difference among the three groups. CONCLUSION ATRA can alveolar, which may be related to the regulation of VEGF, VEGFR-2 and MMP-1, promote the regeneration of best. and early intervention is the best.