全反式维甲酸对肺气肿模型大鼠的干预作用

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。

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

AIM To study the effects of all-trans-retinoid acid(ATRA) on emphysema model in rats at different time periods and its intervention mechanism.METHODS Sixty male Sprague-Dawley(SD) rats,weight from 180 to 220 g,were randomized into 6 groups(n=10),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 intratracheal instillation of 5% papain 1 mL·kg-1,while rats in the group N were treated by intratracheal instillation of normal saline 1 mL·kg-1.Rats in the groups R1,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 R1,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 R1,R2 and R3(P < 0.01) .Compared with the group R2 and R3,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 R1,R2 and R3(P < 0.05),and there was no significant difference among the three groups.CONCLUSION ATRA can promote the regeneration of alveolar,which may be related to the regulation of VEGF,VEGFR-2 and MMP-1,and early intervention is the best.