邻苯二甲酸二丁酯诱导氧化应激及抑制CYP17a1干扰睾酮合成

发布时间：2018-06-16 06:50

本文选题：邻苯二甲酸二丁酯 + 间质细胞　；参考：《卫生研究》2015年03期

【摘要】：目的探讨邻苯二甲酸二丁酯(DBP)导致睾丸氧化损伤与睾酮合成途径的关系及可能的机制。方法 24只健康4周龄雄性Wistar大鼠随机分为对照组(玉米油)及DBP低、中、高剂量组(80、200和500 mg/kg),每组6只,经灌胃染毒每日1次、连续染毒4周。染毒结束后称量动物体重及睾丸和附睾的重量,用生化方法检测睾丸匀浆中丙二醛(MDA)和活性氧自由基(ROS)的含量,抗氧化酶超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶-1(GPx-1)的活性变化,类固醇合成酶3β-HSD1、17β-HSD3的活性,用放射免疫法测定外周血中睾酮、促黄体生成素(LH)、卵泡刺激素(FSH)和睾丸内的睾酮(T)、雄烯二酮(ASD)的水平,用real timeq PCR方法检测St AR、P450scc、3β-HSD1、17β-HSD3、CYP17a1 mRNA水平的表达变化。结果与对照组相比,高剂量组体重、睾丸重量明显减少(P0.05);循环血LH、FSH增高(P0.05),循环血及睾丸内睾酮、睾丸内ASD均降低(P0.05);MDA和ROS的含量明显升高(P0.05),SOD、CAT、GPx-1的活性及3β-HSD1的酶活性均明显降低(P0.05);St AR、P450scc、3β-HSD1、CYP17a1 mRNA降低,17β-HSD3 mRNA升高(P0.05)。中剂量组循环血LH、FSH增高(P0.05),睾丸内T和ASD降低(P0.05);ROS升高(P0.05),GPx-1的活性降低(P0.05);3β-HSD1酶活性减少(P0.05);St AR、P450scc、CYP17a1 mRNA降低(P0.05)。低剂量组所有指标未见有统计学意义的改变。结论 DBP暴露干扰了大鼠睾丸氧化/抗氧化平衡,降低了GPx-1活性,抑制CYP17a1基因的表达,降低睾丸ASD水平,最终抑制间质细胞内睾酮合成。CYP17a1降低是DBP干扰睾酮合成的毒性作用机制之一。
[Abstract]:Objective to investigate the relationship between testis oxidative damage and testosterone synthesis pathway induced by dibutyl phthalate (DBP) and its possible mechanism. Methods Twenty-four healthy 4-week-old male Wistar rats were randomly divided into two groups: control group (corn oil) and low DBP. The weight of the animal and the weight of testis and epididymis were measured by biochemical method. The contents of malondialdehyde (MDA) and reactive oxygen free radical (Ros) in testis homogenate were detected by biochemical method. The activities of superoxide dismutase (SOD), catalase (catalase), glutathione peroxidase (GST) and steroid synthetase (3 尾 -HSD1, 17 尾 -HSD3) were determined by radioimmunoassay. The levels of luteinizing hormone (LHH), follicle stimulating hormone (FSH) and testosterone (TX), androstenedione (ASD) in testis were detected by real timeq. The expression of CYP17a1 mRNA in St ARP450scct3 尾 -HSD1O17 尾 -HSD3 was detected by real timeq PCR. Results compared with the control group, the body weight and testicular weight of the high dose group were significantly lower than that of the control group. ASD in testis decreased the contents of MDA and Ros in P0.05, increased the activity of GPx-1 and decreased the activity of 3 尾 -HSD1 in P0.05, and decreased the expression of CYP17a1 in P450 sccf3 尾 -SD-H1a 1. The expression of 17 尾 -HSD3 mRNA was increased by 17 尾 -HSD3 mRNA. In the middle dose group, the level of circulating blood LHH FSH was increased (P0.05), and the levels of T and ASD in testis were decreased. The activity of P0.05 / Ros was increased. The activity of P0.05 ~ (3) 尾 -HSD1 was reduced by P0.05 / St ARN P450sccCYP17a1 mRNA. There was no significant change in all the indexes in the low dose group. Conclusion DBP exposure interferes with the oxidation / antioxidation balance of rat testis, decreases the activity of GPx-1, inhibits the expression of CYP17a1 gene and reduces the level of ASD in testis. The ultimate inhibition of testosterone synthesis in stromal cells. CYP17a1 is one of the toxic mechanisms by which DBP interferes with testosterone synthesis.
【作者单位】：中国疾病预防控制中心职业卫生与中毒控制所;
【基金】：国家自然科学基金(No.30972447,30150003) 科技部社会公益研究项目(No.2001DIB0059)
【分类号】：R114

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