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目的观察滋肾阴泻相火中药对壬基酚(NP)及双酚A(BPA)染毒大鼠卵巢雌激素合成相关系列酶基因及蛋白表达水平的影响,探讨所用中药拮抗环境内分泌干扰物(EEDs)拟雌激素活性的作用机制。方法 3周龄雌性SD大鼠30只,分为染毒组、治疗组及对照组。染毒组单纯喂饲NP或NP与BPA联合喂饲,治疗组以滋肾阴泻相火中药与染毒物同时喂饲,对照组喂饲溶剂玉米油,疗程15 d。疗程结束时,检测其子宫湿质量及脏器系数,测定其卵巢类固醇急性调节蛋白(StAR)、胆固醇侧链裂解酶(CYP11A1)、芳香化酶(CYP19al)、17-羟类固醇脱氢酶(17-HSD)、17al羟化酶(CYP17al)、3-羟类固醇脱氢酶(3-HSD)的基因表达水平和StAR、CYP11A1、CYP19al蛋白表达水平,进行各组间相互对比。结果染毒组与对照组比较,子宫湿质量、脏器系数增加,卵巢StAR、CYP11A1、CYP19al的基因及蛋白表达水平均明显上调(Pa<0.05),17-HSD、CYP17al、3-HSD的mRNA水平差异无统计学意义;而治疗组与染毒组比较子宫湿质量、脏器系数降低,StAR、CYP11A1的基因及蛋白表达水平均显著下调(Pa<0.05),CYP19al、17-HSD、CYP17al、3-HSD的mRNA水平差异无统计学意义。结论 NP及BPA可诱导卵巢雌激素合成相关酶的表达,促进自身雌激素的生物合成,而中药治疗干预可显著拮抗染毒物质的这种诱导作用,明显抑制染毒动物自身雌激素的生物合成。这可能是中药有效拮抗EEDs拟雌激素活性的主要作用机制之一。
Objective To observe the effects of Zishen Yinxie Fuhuo on gene and protein expression of ovarian estrogen synthesis-related enzymes in nonylphenol (NP) and bisphenol A (BPA) -induced rats, and to explore the effects of traditional Chinese medicine on antagonism of environmental endocrine disruptors (EEDs) mechanism of estrogen activity. Methods Thirty-three-week-old female Sprague-Dawley rats were divided into treatment group, treatment group and control group. The rats in the treatment group were fed with NP or NP alone and BPA. The rats in the treatment group were fed with nourishing Yin, At the end of the course of treatment, the uterus wet mass and organ coefficient were measured and the levels of StAR, CYP11A1, Aromatase (CYP19al), 17-hydroxysteroid dehydrogenase (17) -HSD), 17al hydroxylase (CYP17al), 3-hydroxysteroid dehydrogenase (3-HSD) and the expression of StAR, CYP11A1 and CYP19al protein were compared between groups. Results Compared with the control group, the uterine wet weight and organ coefficient increased, the mRNA and protein expressions of StAR, CYP11A1 and CYP19al in ovary increased significantly (Pa <0.05), and the mRNA expressions of 17-HSD, CYP17al and 3-HSD (P <0.05). The levels of CYP19al, 17-HSD, CYP17al, CYP17al and CYP17al in the treatment group were significantly lower than those in the untreated group 3-HSD mRNA levels were not statistically different. Conclusion NP and BPA can induce ovarian estrogen synthesis-related enzyme expression, and promote their own estrogen biosynthesis, and Chinese medicine treatment can significantly antagonize the exposure of the substance-induced effects, significantly inhibited the animals exposed to their own estrogen biosynthesis . This may be one of the main mechanisms by which traditional Chinese medicine can effectively antagonize the activity of pseudo-estrogens of EEDs.