由环境内分泌干扰物引致食蟹猴性早熟疾病模型建立及滋阴泻火中药治疗干预的实验研究

The Establishment of Environmental Endocrine Disruptors Induced Precocious Puberty Macaca Fascicularis Model and the Intervention of Yin Nourishing Fire Purging Chinese Materia Medica

目的建立灵长类——食蟹猴的由环境内分泌干扰物(environmental endocrine disruptors,EEDs)引致的性早熟疾病模型,验证滋阴泻火中药对EEDs拟雌激素活性的拮抗作用。方法 (1)不同月龄组青春前期雌性食蟹猴喂饲高、低剂量EEDs,通过观察EEDs拟雌激素作用,以确定最佳月龄、染毒剂量及染毒时间。(2)15只青春前期雌性食蟹猴随机分为染毒组、治疗组及对照组,每组5只。染毒组喂饲壬基酚(nonylphenol,4-NP)及双酚A(bisphenol,BPA),治疗组将染毒物质及滋阴泻火中药合剂同时喂饲,对照组喂饲溶剂玉米油。疗程4周。疗程完成时,检测血清雌激素水平、阴道脱落细胞成熟指数,取出子宫,测定其子宫湿重、子宫内膜及环形平滑肌厚度、子宫内膜上皮细胞及腺上皮细胞高度。结果 (1)20月龄为最佳染毒月龄,低剂量EEDs为最佳染毒剂量,4周为最佳染毒时间。(2)与对照组比较,染毒组血清雌激素水平明显升高,阴道脱落细胞成熟指数显著增加,子宫湿重、子宫内膜厚度及环形平滑肌厚度、子宫内膜上皮细胞及腺上皮细胞高度显著增加(P<0.05)。与染毒组比较,治疗组上述指标均显著降低(P<0.05)。结论本研究成功地建立了灵长类——食蟹猴由EEDs引致性早熟的疾病模型,证实了EEDs具有显著的拟雌激素活性,并验证了滋阴泻火中药合剂对其拟雌激素活性具有显著的拮抗作用。

Objective To establish the environmental endocrine disruptors （EEDs） induced precocious puberty macaca fascicularis model, thus verifying the antagonism of yin nourishing fire purging Chinese materia medica （YNFPCMM） against the estrogenic effects. Methods （1） The female prepubescent monkeys at different months old were fed with high dose and low dose EEDs. By observing EEDs＇ estrogenic effects, the optimal age, the optimal exposure dose, and the optimal exposure time were determined. （2） Fifteen female prepubescent monkeys were randomly divided into the exposure group, the treatment group, and the control group, 5 in each group. Those in the exposure group were fed with EEDs such as nonylphenol （4-NP） and bisphenol A （BPA）. Those in the treatment group were fed with EEDs and YNFPCMM. Those in the control group were fed with dissolvent such as corn oil. The therapeutic course was 4 weeks. By the end of the treatment, the serum estrogen level was measured and the maturation index of the vaginal keratinocytes was calculated. The uterus was extracted to measure the wet weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height. Results （1） Twenty month was the optimal exposure age. The low dose EEDs was the best exposure dose, and 4 weeks was the optimal exposure time. （2） Compared with the control group, the serum estrogen level obviously increased, the maturation index of the vaginal keratinocytes significantly increased, the wet uterus weight, the endometrial thickness, the ring-shaped myo- metrium thickness, the endometrial epithelial cells, and the glandular epithelium height significantly increased in the exposure group （ P 〈0.05）. Compared with the exposure group, the aforesaid indices significantly decreased in the treatment group （ P 〈0.05）. Conclusions The EEDs induced precocious puberty macaca fascicularis model was successfully established in this study. The EEDs were proved to have estrogenic-like activities. YNFPC- MM was proved to have significant antagonism like estrogenic activities.