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槲皮素对 Aroclor 1254 诱导的孕鼠 CYP 和细胞因子表达的影响。

Effects of quercetin on Aroclor 1254-induced expression of CYP and cytokines in pregnant rats.

机构信息

a College of Life Science and Food Engineering , Hebei University of Engineering , Handan , China.

b College of Life Sciences , Hebei Agricultural University , Baoding , China.

出版信息

J Immunotoxicol. 2019 Dec;16(1):140-148. doi: 10.1080/1547691X.2019.1604585.

DOI:10.1080/1547691X.2019.1604585
PMID:31290710
Abstract

The present study aimed to investigate the protective effect of quercetin on polychlorinated biphenyls (PCB)-induced liver and embryo damage in pregnant Sprague-Dawley rats. Pregnant rats were divided into five groups, and then were orally gavaged daily with peanut oil (vehicle) or a commercial PCB mixture (Aroclor 1254) - with or without co-treatment with 75, 150, or 300 mg/kg quercetin - on gestation days (GD) 4-7. At GD 9, all rats were euthanized, and their blood, liver, and uterus were collected. Expressions of mRNA and protein in liver, cytokines (IFNγ, IL-2, IL-4, and IL-6) and IFNγ/IL-4 ratios in liver and sera, liver morphology, and the status of implanted embryos were analyzed. The results showed Aroclor 1254 treatment alone caused hepatic cord damage (i.e. cell disorganization, swelling, decreased cytoplasm, vacuolization), and that quercetin co-treatment appeared to mitigate this damage. Similarly, levels of and mRNA in livers of Aroclor 1254-only-treated rats were significantly higher than those in rats co-treated with quercetin. Hepatic and sera levels of IFNγ, IL-2, IL-6, and IFNγ/IL-4 ratios, and the ratio of delayed-development embryos, all increased in Aroclor 1254-treated rats, but were relatively decreased as a result of quercetin co-treatments. IL-4 levels were decreased by Aroclor 1254 and tended to increase back to normal when quercetin was used. The results indicated that quercetin imparted a protective effect against Aroclor 1254-induced toxicity in pregnant rats, in part, by modulating levels of important pro-inflammatory cytokines and reducing induced CYP1A1 and CYP2B1 expression.

摘要

本研究旨在探讨槲皮素对多氯联苯(PCB)诱导的孕 Sprague-Dawley 大鼠肝和胚胎损伤的保护作用。将孕鼠分为五组,然后分别在妊娠第 4-7 天每天口服给予花生油(载体)或商业 PCB 混合物(Aroclor 1254),同时给予 75、150 或 300mg/kg 槲皮素进行联合治疗。在妊娠第 9 天,所有大鼠均被安乐死,采集其血液、肝脏和子宫。分析肝脏中 mRNA 和蛋白的表达、肝脏和血清中的细胞因子(IFNγ、IL-2、IL-4 和 IL-6)和 IFNγ/IL-4 比值、肝脏形态以及植入胚胎的状态。结果表明,Aroclor 1254 单独处理会导致肝索损伤(即细胞排列紊乱、肿胀、细胞质减少、空泡化),而槲皮素联合处理似乎减轻了这种损伤。同样,Aroclor 1254 单独处理大鼠肝脏中 和 mRNA 的水平明显高于槲皮素联合处理大鼠。Aroclor 1254 处理大鼠肝和血清中 IFNγ、IL-2、IL-6 和 IFNγ/IL-4 比值以及发育迟缓胚胎的比例均升高,但由于槲皮素的联合处理而相对降低。IL-4 水平因 Aroclor 1254 而降低,当使用槲皮素时趋于恢复正常。结果表明,槲皮素通过调节重要的促炎细胞因子水平和降低诱导的 CYP1A1 和 CYP2B1 表达,对孕鼠 Aroclor 1254 诱导的毒性具有保护作用。

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