异黄酮改构化合物F11雌激素效应初步研究

目的初步研究异黄改构化合物F11的雌激素效应。方法构建去双卵巢大鼠动物模型,经腹腔注射F11[15、50、150 mg/(kg.d)3个剂量组(F11-15组、F11-50组、F11-150组)]共10周,同时设置阴性对照组,阳性对照组(E2)和假手术组,统计分析各组大鼠子宫湿质量/体质量情况,HE染色观察用药前后阴道涂片和子宫内膜变化情况;Westernblot检测子宫内膜组织ERα和ERβ的表达情况。结果 F11-50及F11-150组大鼠子宫湿质量/体质量显著高于阴性对照组(P<0.05),且F11-150组与E2和假手术组无显著差别(P>0.05)。阴性对照组大鼠阴道涂片以炎细胞为主,F11各组以角化上皮细胞为主,与E2和假手术组相似;F11各组较阴性对照组子宫内膜腺体数目增多,腺腔增大,F11-150组与E2和假手术组相似。F11各组ERα及ERβ蛋白表达均强于阴性对照组(P<0.05),其中ERα表达弱于E2和假手术组(P<0.01),而F11-150组ERβ的表达强于E2和假手术组(P<0.05)。结论 F11在增加去双卵巢大鼠子宫湿质量、阴道上皮成熟及子宫内膜ER的表达等方面均表现出雌激素效应,该效应主要通过ERβ介导。

Preliminary study of estrogenic effect of isoflavone derivative F11 in vivo

Objective To study the estrogenic effect of isoflavone derivative F11 in vivo.Methods The ovariectomized rat models were constructed,and the rats were divided into a negative control group(normal saline),a positive control group [estradiol,50 μg/(kg·d)],a sham operation group and three F11 groups including a F11-15 group,a F11-50 group and a F11-150 group [intraperitoneal injection of F11 with 15,50 and 150 mg/(kg·d),respectively].After the treatment for 10 weeks,the ratio of rat uterus wet weight/body weight was analyzed,and the vaginal smear and endometrium were observed by HE staining.The expression of estrogen receptor(ER) α and ERβ in endometrial tissues was determined by Western blotting.Results The ratio of rat uterus wet weight/body weight in the F11-50 group and F11-150 group was significant higher than that of the negative control group(P<0.05),but the ratio of the F11-150 group was not significantly different from that of the positive control group or sham operation group(P>0.05).There were mainly inflammatory cells in the vaginal smear of the negative control group and keratinized epithelial cells in the vaginal smear of the F11 groups.The HE staining results showed that the quantity of endometrial glands and the size of gland cave in all the three F11 groups were greater than those of the negative control group,and those of the F11-150 were the same as the positive control group and sham operation group.The expression levels of ERα and ERβ in endometrial tissues in the F11 groups were significantly higher than those in the negative control group(P<0.05).The ERα expression level of the F11 groups was significantly lower than that of the positive control group and sham operation group(P<0.01),and the ERβ expression level of the F11-150 group was significantly higher than that of the positive control group and sham operation group(P<0.05).Conclusion F11 exhibits estrogenic effect on increasing uterus wet weight,promoting vaginal epithelium maturation and upregulating ER expression in endometrium of ovariectomized rats mainly through ERβ.