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妊娠和哺乳期壬基酚暴露对卵清蛋白诱导的哮喘大鼠幼仔气道炎症的影响。

Effect of gestational and lactational nonylphenol exposure on airway inflammation in ovalbumin-induced asthmatic rat pups.

机构信息

School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, PR China.

School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, PR China.

出版信息

Chemosphere. 2020 Jul;250:126244. doi: 10.1016/j.chemosphere.2020.126244. Epub 2020 Feb 19.

Abstract

To investigate the effect of gestational and lactational nonylphenol (NP) exposure on airway inflammation in ovalbumin (OVA)-induced asthmatic pups. Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 7 to postnatal day 21. The results showed that the NP content in the lung tissues of pups in the 100 mg/kg NP group was significantly higher than that of the control group (P = 0.004). In the 100 mg/kg NP group, the infiltration of lymphocytes and eosinophils with thicken smooth muscle layer and inflammatory cells in the lumen were observed in the lung tissues of pups. Osmiophilic lamellar bodies were found in the cytoplasm of type II epithelial cells; mitochondria were clearly swollen. Compared with the control group, the levels of interleukin-4 (IL-4) in BALF (P = 0.042) and ovalbumin-specific serum immunoglobulin E (OVA-sIgE) (P = 0.005) in the OVA group were significantly higher. 25 mg/kg NP-OVA co-exposure synergistically decreased nuclear factor-κB (NF-κB) mRNA expression in the lung tissues of pups; Exposure to 50 mg/kg NP combined with OVA antagonized the increased expression of high mobility group box 1 (HMGB1) mRNA in the lung tissue. The combined exposure to 50 mg/kg NP and OVA synergistically increased HMGB1 protein expression in the lung tissues. 25 mg/kg NP-OVA co-exposure antagonized the increased nuclear factor-κB (NF-κB) protein expression in the lung tissues. There was a positive correlation between NP content and HMGB1 protein expression in the lung tissue of asthmatic pups (r = 0.602, P < 0.001). In conclusion, gestational and lactational exposure to 100 mg/kg NP in maternal rats exacerbated airway inflammation in OVA-induced asthmatic pups, and there is an interactive effect between NP and OVA. When the perinatal rats were exposed to 100 mg/kg NP, the levels of HMGB1 and NF-κB in the lung tissues of OVA-induced asthmatic pups were increased.

摘要

为了研究妊娠和哺乳期壬基酚(NP)暴露对卵清蛋白(OVA)诱导的哮喘幼崽气道炎症的影响。从妊娠第 7 天到产后第 21 天,分别用剂量为 25mg/kg/天(低剂量)、50mg/kg/天(中剂量)、100mg/kg/天(高剂量)的 NP 和花生油(载体对照)灌胃。结果表明,100mg/kg NP 组幼崽肺组织中的 NP 含量明显高于对照组(P=0.004)。在 100mg/kg NP 组,幼崽肺组织中观察到淋巴细胞和嗜酸性粒细胞浸润,平滑肌层增厚,管腔中有炎症细胞。在 II 型上皮细胞的细胞质中发现亲脂性板层小体;线粒体明显肿胀。与对照组相比,OVA 组 BALF 中的白细胞介素-4(IL-4)水平(P=0.042)和卵清蛋白特异性血清免疫球蛋白 E(OVA-sIgE)(P=0.005)明显升高。25mg/kg NP-OVA 共暴露协同降低幼崽肺组织中核因子-κB(NF-κB)mRNA 的表达;50mg/kg NP 暴露与 OVA 联合拮抗肺组织中高迁移率族蛋白 1(HMGB1)mRNA 的增加表达。50mg/kg NP 与 OVA 联合暴露协同增加肺组织中 HMGB1 蛋白的表达。25mg/kg NP-OVA 共暴露拮抗肺组织中 NF-κB 蛋白表达的增加。哮喘幼崽肺组织中 NP 含量与 HMGB1 蛋白表达呈正相关(r=0.602,P<0.001)。综上所述,母鼠妊娠和哺乳期暴露于 100mg/kg NP 加重了 OVA 诱导的哮喘幼崽的气道炎症,NP 与 OVA 之间存在交互作用。当围产期大鼠暴露于 100mg/kg NP 时,OVA 诱导的哮喘幼崽肺组织中 HMGB1 和 NF-κB 的水平增加。

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