Chen Li, Chen Jiao, Xie Chang Ming, Zhao Yan, Wang Xiu, Zhang Yun Hui
Minhang District Center for Disease Control and Prevention, Shanghai 201101, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
Biomed Environ Sci. 2015 Mar;28(3):190-8. doi: 10.3967/bes2015.025.
To evaluate the effect of diisononyl phthalate (DINP) exposure during gestation and lacta- tion on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it.
Female Wistar rats were treated with DINP at different dosages (0, 5, 50, and 500 mg/kg of body weight per day). The pups were sensitized and challenged by ovalbumin (OVA). The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin (HE) staining; and the relative cytokines in phosphoinositide 3-kinase (PI3K)/Akt pathway were measured by enzyme-linked immunosorbent assay (ELISA) and western blot analysis.
There was no significant difference in DINP's effect on airway hyperresponsiveness (AHR) between male pups and female pups. In the 50 mg/(kg·d) DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance (RI) compared with those from controls (P<0.05). Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/(kg·d) DINP-treated group. However, in the 5 and 500 mg/(kg·d) DINP-treated pups, no significant effects were observed.
There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.
评估孕期和哺乳期邻苯二甲酸二异壬酯(DINP)暴露对幼崽过敏反应的影响,并探讨磷酸肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路在其中的作用。
将雌性Wistar大鼠分别给予不同剂量(0、5、50和500 mg/kg体重/天)的DINP处理。用卵清蛋白(OVA)对幼崽进行致敏和激发。评估气道反应;通过苏木精和伊红(HE)染色进行气道组织学研究;采用酶联免疫吸附测定(ELISA)和蛋白质免疫印迹分析检测PI3K/Akt信号通路中相关细胞因子。
DINP对雄性和雌性幼崽气道高反应性(AHR)的影响无显著差异。在50 mg/(kg·d) DINP处理组中,与对照组相比,幼崽对OVA的气道反应显著增加,肺阻力(RI)显著增强(P<0.05)。在50 mg/(kg·d) DINP处理组的幼崽中观察到Akt磷酸化增强、核因子κB(NF-κB)易位以及Th2细胞因子表达增加。然而,在5和500 mg/(kg·d) DINP处理的幼崽中未观察到显著影响。
DINP对幼崽过敏性气道炎症有佐剂作用。母体DINP暴露可能部分通过上调PI3K/Akt信号通路促进幼崽OVA诱导的过敏性气道反应。