四氯二苯并二恶英对SZ95人皮脂腺细胞细胞色素P4501A1表达的影响及其意义  

Effect of tetrachlorodibenzo-p-dioxin on the expression of cytochrome P4501A1 in human SZ95 sebocytes and its significance

作　　者：余茜[1] 胡婷婷[1] 莫小辉[1] 章楚光[1] 夏隆庆[2] ChristosC.Zouboulis 鞠强[1,3] 

机构地区：[1]安徽医科大学上海皮肤病临床学院,上海200433 [2]中国医学科学院北京协和医学院皮肤病医院 [3]Dermatopharmakologie.StadtischesKlinikumsDessau.Deutsch-land(ChristosC.Zouboulis [4]上海交通大学医学院附属仁济医院皮肤科

出　　处：《中华皮肤科杂志》2013年第8期557-560,共4页Chinese Journal of Dermatology

基　　金：国家自然科学基金（81071310）;上海市自然科学基金（09ZR1428400）

摘　　要：目的探讨环境污染物2,3，7，8-四氯二苯并二恶英（TCDD）影响人皮脂腺细胞的细胞色素P4501A1（CYP1A1）分子信号途径及氯痤疮的发生机制。方法实时荧光PCR研究10nmol／LTCDD作用SZ95人皮脂腺细胞2h后CYP1A1mRNA表达的变化；细胞免疫组化和斑点印迹法研究10nmol／LTCDD作用SZ95人皮脂腺细胞3d后蛋白表达变化情况。结果实时荧光PCR研究显示，CYP1A1mRNA在SZ95人皮脂腺细胞呈低量表达，在10nmol／LTCDD作用下，CYP1A1mRNA表达增强了5．622倍，差异有统计学意义（P〈0．05）。细胞免疫组化显示，CYP1A1蛋白在SZ95人皮脂腺细胞核及胞质中低量表达，在10nmol／LTCDD作用下表达明显增强。斑点印迹法证实，10nmol／LTCDD作用于SZ95人皮脂腺细胞3d后CYPIAl蛋白相对定量值（4．233±0．252）显著高于未加药的阴性对照组（0．123±0．208），差异有统计学意义（P〈0．05）。结论CYP1A1mRNA和蛋白在SZ95人皮脂腺细胞上呈低量表达，但在TCDD作用下表达被激活，体外证明CYP1A1是TCDD影响人皮脂腺细胞异常分化的AhR下游靶位基因之一。Objective To estimate the effect of the enviromental pollutant 2, 3, 7, 8-tetrachlorodibenzo-p- dioxin （TCDD）, a representative of the dioxin family, on the expression of cytochrome P4501A1 （CYP1A1） in cultured human immortalized SZ95 sebocytes in vitro, so as to improve understanding of the pathogenesis of ehloracne. Methods SZ95 sebocytes were cultured with or without the presence of 10 nmol/L TCDD for two hours or three days. Real time fluorescence-based PCR was performed to quantify the mRNA expression of CYP1A1, immunohistochemistry and Westem blot to determine the expression level of CYP1A1 protein, in the SZ95 cells. Chi-square test was done to compare the protein and mRNA expressions of CYP1A1 between untreated and treated SZ95 cells. Results Real time PCR showed that the mRNA expression of CYP1AI was low in SZ95 sebocytes, and increased by 5.622 times after 2-hour treatment with TCDD （P 〈 0.05）. Immunohistochemistry revealed a weak expression of CYP1A1 protein in the cytoplasm and nuclei of untreated SZ95 sebocytes, which was also significantly enhanced by the TCDD treatment. Western blot results showed that the relative expression level of CYP1A1 protein was 4.233 ±0.252 in SZ95 sebocytes treated by TCDD for three days, significantly higher than that in untreated sebocytes（0.123 ± 0.208, P 〈 0.05）. Conclusions There is a low expression of CYP1A1 mRNA and protein in SZ95 seboeytes, which can be upregulated by TCDD, suggesting that the CYP1A1 gene is a downstream target of the arvl hydrocarbon receptor responsible for the abnormal differentiation of human seboc,ctes.

关 键 词：细胞色素P4501A1 四氯二苯并二恶英 皮脂腺 细胞 

分 类 号：X5[环境科学与工程—环境工程] R[医药卫生]