滋肾阴泻相火中药对环境内分泌干扰物染毒大鼠生殖器官雌激素受体表达的影响

Effect of Chinese Herbs for Nourishing Shen-Yin and Removing Xiang-Fire on Estrogen Receptor Expression in Reproductive Organ of Rats Contaminated with Environmental Endocrine Disruptor

目的观察滋肾阴泻相火中药对壬基酚及双酚A染毒大鼠子宫、卵巢雌激素受体(ER)基因和蛋白表达的影响,探讨该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大鼠染毒组单纯喂饲壬基酚或壬基酚与双酚A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,给药15天,分别检测子宫湿重及脏器系数、子宫及卵巢ER基因和蛋白表达水平。结果染毒组与对照组比较,子宫湿重及子宫系数增加,ER蛋白表达显著上调;卵巢ERα、ERβ的基因表达及蛋白水平显著上调(P<0.05)。治疗组与染毒组比较,子宫湿重、子宫系数降低,ER的蛋白表达显著下调;卵巢ERα、ERβ的基因表达及蛋白水平显著下调(P<0.05)。结论EEDs对生殖器官有显著的拟雌激素作用,而滋肾阴泻相火中药对EEDs的拟雌激素活性具有显著的拮抗作用。中药的治疗干预可使生殖器官ER基因、蛋白表达显著下调,从而显著降低生殖器官对EEDs的敏感性,这可能是所用中药有效拮抗EEDs拟雌激素活性的主要作用机制之一。

Objective To investigate the effect of Chinese herbs for nourishing Shen-yin and removing Xiang-fire （NYRF） on estrogen receptor （ER） expression in uterus and ovary of rats contaminated with nonylphenol （NP） or its bisphenol A （BPA） mixture, for exploring the action mechanism of NYRF in antagonizing the estrogen-mimetic activity of environmental endocrine disruptors （EEDs）. Methods EEDs contaminated female SD rats, 3-week old, were divided into two groups, the treated group fed with NYRF and the control group with corn oil during the same period of contaminating for 15 days. The wet weight （WW） and organ coefficient （OC） of uterus in rats, as well as the ER protein and mRNA expressions in rat＇s uterus and ovary were detected and compared. Resuits As compared with normal range, WW and OC increased significantly in the contaminated rats of the control group, with significantly down-regulated ER protein expression in uterus, and expressions of ERα and ERβgene and protein in ovary （P 〈0.05）. While in the treated group, the above-mentioned abnormalities of various indictors were markedly reversed to a certain extent （ P 〈0. 05）. Conclusion EEDs show estrogenic-mimetic action on productive organs, which could be antagonized by NYRF, resulting in the down-regulated mRNA and protein expressions of ER in reproductive organs, so as to reduce the sensibility of reproductive organs to EEDs, which is probably one of the acting mechanisms of NYRF.