滋肾阴泻相火中药对环境内分泌干扰物染毒大鼠卵巢雌激素合成相关酶表达的影响

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。

Effects of Chinese Herbs for Nourishing Yin and Removing Fire on Expression of Enzymes Involved in Estrogen Metabolism of Female Rats' Ovary with Environmental Endocrine Disruptors

Objective To investigate the effects of Chinese Herbs for Nourishing Yin and Removing Fire(NYRF) on expression of enzymes involved in the estrogen metabolism in ovary of female rats with nonylphenol(NP) and mixture of nonylphenol and bisphenol A(BPA)and to discuss the mechanism of NYRF′s antagonism to the estrogenic effect. Methods Twenty-one days immature female SD rats were given orally nonylphenol and a mixture of NP and BPA,while giving chinese herbs treatment for 15 days,and the uterine wet weight,the uterus organ coefficient and steroidogenic acute regulatory protein(StAR);cytochrome P450,family 11,subfamily a,polypeptide 1(CYP11A1);cytochrome P450,family 19,subfamily a,polypeptide 1(CYP19al);17β-hydroxysteroid dehydrogenase(17β-HSD);cytochrome P450,family 17,subfamily a,polypeptide 1(CYP17al);3β-hydroxysteroid dehydrogenase(3β-HSD) gene expression and StAR,CYP11A1,CYP19al protein expression in ovary,were detected. Results Uterine wet weight,Uterus organ coefficient,the gene and protein expression of StAR,CYP11A,CYP19al in ovary significantly increased in NP group and NP+BPA group as compared with those in vehicle control group.The expression levels,including mRNA of 17-HSD,CYP17al,3-HSD were not significantly different.After treatment with NYRF,uterine wet weight,uterus organ coefficient,the upregulated-mRNA levels and the protein expression of StAR,CYP11A1 significantly reduced while the mRNA levels of CYP19al,17-HSD,CYP17al,3-HSD were not statistically different. Conclusions NP and BPA can promote their own estrogen biosynthesis by inducing the enzyme expression of ovarian estrogen biosynthesis.NYRF can suppress the gene and protein expression which is involved in the estrogen metabolism in ovary of female with NP and BPA,which may be a part of the mechanism of NYRF′s antagonism to the estrogenic effect of environmental endocrine disruptors.