邻苯二甲酸二乙基己基酯对子代大鼠肺损伤的作用及其机制  

The effect of DEHP on lung injury and its mechanisms in offspring rat

作　　者：林刻智[1] 卢清艺 林中民 黄卡特[2] 余帅帅[3] 陈国荣[2] 

机构地区：[1]温州医科大学基础医学实验中心,浙江温州325035 [2]温州医科大学附属第一医院病理科,浙江温州325035 [3]温州医科大学电镜室,浙江温州325035

出　　处：《温州医学院学报》2013年第8期491-495,共5页Journal of Wenzhou Medical College

基　　金：国家自然科学基金资助项目(30671736);浙江省自然科学基金资助项目(LY12H26002);温州市科技局科研基金资助项目(Y20100130)

摘　　要：目的:研究邻苯二甲酸二乙基己基酯(DEHP)对出生后第21天(PND21)子代大鼠肺脏的损伤作用及其机制。方法:受孕SD大鼠24只,随机均分为正常对照(NC)组、低剂量染毒(L)组、中剂量染毒(M)组和高剂量染毒(H)组,从怀孕第1天至产后PND21,每天给予不同剂量DEHP(0、10、100、750 mg·kg-1·d-1)母鼠灌胃。获取PND21子代大鼠肺泡巨噬细胞(AM)并培养。分别测定AM内超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性;Masson染色及光镜、电镜观察肺组织病理学改变;免疫组化和RT-PCR检测肺组织骨桥蛋白(OPN)及其基因表达。结果:H组肺泡隔增厚,肺间质细胞增多,肺泡数目减少;M、H组肺细小动脉以及肺间质胶原纤维沉积较NC组增多,以H组最为显著;超微结构显示M、H组肺泡II型上皮细胞核固缩,板层小体空泡化,线粒体肿胀、变圆,嵴变短;M、H组AM内SOD和GSH-PX酶活性明显低于NC组(P<0.05);M、H组OPN及其mRNA表达较NC组显著上调(P<0.05),L组与NC组相比,差异无统计学意义(P>0.05)。结论:DEHP对PND21子代大鼠肺损伤主要表现为肺间质纤维化,肺泡II型上皮细胞损伤、AM抗氧化能力的下降及OPN的表达升高可能是其机制。Objective： To observe the effect of Di-ethylhexyl phthalate （DEHP） on the lung injury of offspring rat and to explore its mechanism. Methods： Twenty-four pregnant Sprague-Dawley rats were randomly divided into 4 groups according to the different dosages of DEHP. The pregnant rats were exposed to DEHP at dose of 0 mg· kg-1· d-1 （NC）, 10 mg· kg-1· d-1 （L）, 100 mg· kg-1· d-1（M） or 750 mg· kg-1· d-1（H） by gavage from gestation day 1 （GD1） to postnatal day21 （PND21） respectively. Alveolar macrophages （AM） were collected, isolated and cultured. The activity of glutathione peroxidase （GSH-PX） and superoxide dismutase （SOD） of AM was detected biochemically. The morphological changes of the lung were observed by transmission electron microscope （TEM） and light microscopy （LM）, and the collogen fiber was disclosed by Masson staining. The expression of osteopontin（OPN） protein from the lung was determined by immu- nohistochemistry （IHC）. The OPN mRNA expression was detected by RT-PCR. Results： There were thick- ened alveolar septa, increased cellular number in interstitium and deceased alveolar number in H group. Under Masson staining, there was increased collogen fiber in interstitium and surrounding the arteriol of the lung from M, H group, compared with the control group, and it was more obvious in H group. Ultrastractrnally, it was showed that there were pyknosis, vaculated lamellar body and swelling mitochonchea of type lI alveolar epithelial cells in M and H group. The activity of SOD and GSH-PX in AM from M and H group was decreased, compared with that of control group （P 〈 0.05）. The protein and mRNA expression of OPN in M and H group was higher than that of control group. Conclusion： DEHP could damage the lung of offspring rats by causing interstitial fibrosis, the impairment of type II alveolar epithelial cells and ant-oxidative activity of AM and the increased expression of OPN may be involved in it.

关 键 词：邻苯二甲酸二乙基己基酯 巨噬细胞 大鼠 骨桥蛋白 肺泡II型上皮细胞 肺损伤 

分 类 号：R363[医药卫生—病理学]