新型雌激素哌嗪雌酚酮对雌激素受体表达的影响及其对靶基因的转录激活作用

目的探讨哌嗪雌酚酮对雌激素受体表达的影响及其对靶基因ERE的转录激活作用。方法小鼠去卵巢后,每天灌服不同剂量的哌嗪雌酚酮(0.5、1、2mg.kg-1)以及雌酚酮(0.71mg.kg-1),连续42d,采用免疫组织化学的方法观察哌嗪雌酚酮对去卵巢小鼠子宫中两种雌激素受体(ERα和ERβ)蛋白表达的影响;采用Tfx-50脂质体共转染目的基因和报告基因于MCF-7细胞株,探讨哌嗪雌酚酮对ERE的转录激活作用。结果与去卵巢模型组比较,哌嗪雌酚酮各剂量组能够上调子宫组织中两种雌激素受体亚型的表达(有剂量依赖性),对ERα亚型作用明显于ERβ;哌嗪雌酚酮能够激活雌激素受体的经典信号途径,与等摩尔剂量的雌酚酮相比仅表现出弱雌激素活性。结论哌嗪雌酚酮能够上调子宫组织中ERs的表达;与雌酚酮比较,其对靶基因ERE的转录激活作用非常微弱。     

槲皮素对去卵巢大鼠生殖系统及骨密度的影响

目的探讨槲皮素在体内的雌激素样作用。方法健康雌性SD大鼠48只按体重随机分为6组：假手术组（SHAM）、单纯去卵巢组（OVX）、17β-雌二醇组[ERT，0．1mg／（kg·d）]、高剂量槲皮素组[QH，300mg／（kg·d）]、中剂量槲皮素组[QM，150mg／（kg·d）]、低剂量槲皮素组[QL，75mg／（kg·d）]。除假手术组外其余各组均切除双侧卵巢，术后1周开始给药，连续16周。给药期间每天观察阴道脱落细胞涂片。处死大鼠后，测量子宫重量计算子宫系数，病理切片观察子宫内膜及腺体，测量腰椎和股骨骨密度。结果槲皮素能使去卵巢大鼠阴道上皮细胞角化、子宫系数增加、腺体及内膜增生，骨密度增加（P〈0．05）。结论槲皮素在去卵巢大鼠体内具有弱雌激素样作用，能减轻雌激素缺乏导致的生殖系统萎缩，且能防止骨量丢失。     

乙烯雌酚对雌鼠生殖内分泌及下丘脑ERαmRNA表达的影响

目的观察性类固醇激素——乙烯雌酚对雌鼠生殖内分泌及下丘脑ERαmRNA表达的影响。方法健康大鼠32只随机取16只作正常对照组,其余16只均采取双侧卵巢切除手术加夹尾激怒法造模,造模成功后为观察组。两组分别连续灌胃生理盐水与乙烯雌酚4周,采用形态学观察生殖内分泌情况,采用逆转录聚合酶链反应(RT-PCR)法测定大鼠下丘脑ERαmRNA表达。结果与正常对照组比较,观察组大鼠肾上腺湿重系数明显降低(P<0.01)。同时子宫形态也有明显变化。观察组大鼠下丘脑ERαmRNA的表达明显下降(P相似文献   

绝经后妇女阴道炎的临床治疗与妇科分析研究

目的研究乙烯雌酚与氟哌酸、甲硝唑联合治疗老年性阴道炎的临床疗效。方法将240例绝经后阴道炎患者随机分成雌激素与氟哌酸、甲硝唑联合治疗(观察组)和单用乙烯雌酚治疗(对照组),两组进行临床治疗效果对照。结果乙烯雌酚与抗菌联合治疗效果明显优于单用雌激素治疗组。结论雌激素配合氟哌酸、甲硝唑用于局部给药治疗绝经后阴道炎疗效确切、经济、实用。     

固肾调经片的雌激素样作用考察

目的:研究固肾调经片的雌激素样作用。方法:选取幼年雌性小白鼠,予固肾调经片浸膏灌胃,观察小白鼠阴道角化上皮细胞数变化并计数;称取小鼠子宫、卵巢质量,计算子宫/体质量比值、卵巢/体质量比值;测定小鼠血清中雌二醇的含量。结果:固肾调经片能明显增加幼年雌性小鼠阴道角化细胞数量,使幼年小鼠子宫与卵巢重量明显增加,使小鼠血清中雌二醇含量明显增加,且作用呈明显的剂量依赖性。实验组与空白对照组相比,各指标间差异均有统计学意义(P<0.05或0.01)。结论:固肾调经片有提高小鼠雌激素水平的作用。     

花粉的雌激素活性测定及微核试验

本文以幼小鼠子宫增重法和去卵巢大鼠阴道细胞角化法测定了花粉的雌激素活性,结果表明花粉无雌激素活性和抗雌激素活性。小鼠每天以1和5g/kg花粉灌胃,连续二个月,微核试验阴性。     

吡硫翁锌乳膏对银屑病样模型小鼠的药效学研究

目的：研究吡硫翁锌乳膏抗银屑病的作用。方法：采用小鼠雌激素期的阴道上皮模型和鼠尾鳞片表皮银屑病样皮损模型,观察吡硫翁锌乳膏抗银屑病的作用。在小鼠雌激素期的阴道上皮模型中,吡硫翁锌乳膏经小鼠阴道给药,连续给药14 d,观察小鼠阴道上皮分裂指数的变化。在鼠尾磷片表皮银屑病样皮损模型中,吡硫翁锌乳膏被涂抹于小鼠尾部,连续给药14 d,观察鼠尾含有颗粒层的鳞片数目的变化,及对小鼠上皮细胞有丝分裂及表皮细胞分化的影响。结果：经吡硫翁锌乳膏处理后,小鼠阴道上皮分裂指数明显降低,鼠尾含有颗粒层的鳞片数目明显增加。结论：吡硫翁锌乳膏能明显抑制阴道上皮细胞分裂,促进尾鳞片表皮颗粒层形成,具有潜在的抗银屑病样的作用。     

哌嗪雌酚酮对去卵巢大鼠骨代谢的作用

目的研究哌嗪雌酚酮(一种新合成雌激素哌嗪类衍生物)对去卵巢大鼠骨代谢及子宫的作用。方法 雌酚酮(E) 0.75 mg·kg^-1·d^-1,哌嗪雌酚酮(P-E) 1和10 mg·kg^-1·d^-1,ig共90 d,骨形态计量学测量。结果去卵巢大鼠子宫萎缩,血清胆固醇升高,骨量减少伴骨高转化的改变。E组与去卵巢组比,子宫重量增加,血清胆固醇降低,骨高转化降低。P-E(1 mg)组与去卵巢组比,子宫重量轻微增加,骨量增加,骨形成和骨吸收均维持在去卵巢组的高水平。P-E(10 mg)组比低剂量组增加更多的骨量,但其作用机理与雌酚酮相同,明显地降低骨转化。结论哌嗪雌酚酮可预防去卵巢大鼠所致的骨丢失。低剂量(1 mg)组对子宫未见明显副作用。     

五味子对去卵巢小鼠的记忆保持和海马NOS神经元表达的影响

目的：研究五味子（Fructus Schisandrae Chinensis）改善记忆与类雌激素作用的关系，并探讨相关的作用机制。方法：采用一次性被动回避反应行为学方法研究五味子对去卵巢小鼠记忆能力的影响；NADPH—d酶组化染色观察五味子对小鼠海马亚区一氧化氮合酶（NOS）阳性神经元形态及数日的影响。结果：去卵巢可明显降低小鼠的记忆能力，同时降低海马各区NOS阳性神经元数目。五味子醇提物具有改善去卵巢小鼠记忆保持的能力，显著增加海马各区NOS阳性神经元数目；五味子脂提物却明显抑制去卵巢小鼠的记忆保持，相应降低海马各区NOS阳性神经元的数目。结论：五味子改善记忆保持与类雌激素作用有关，其类雌激素作用的主要成分存在于乙醇提取物中，但五味子脂提物存在拮抗类雌激素的作用。影响海马各区NOS阳性神经元的合成及分布可能是五味子醇提物的类雌激素作用机制之一。     

骨靶向新化合物四环素 哌嗪雌酚酮的雌激素活性测定

为寻找副作用小而有抗骨质疏松作用的雌激素衍生物,用雌激素受体结合竞争抑制实验,小鼠阴道细胞学实验,幼雌小鼠子宫重量法分别研究了骨靶向新化合物四环素-哌嗪雌酚酮(XW630)的雌激素活性。结果表明:XW630与子宫组织雌激素受体的相对亲和力为0.011,而雌酚酮与雌二醇分别为0.325及1.000。XW630的雌激素活性指数及细胞学实验均表明XW630的雌激素活性明显小于雌酚酮及雌二醇。提示有抗骨质疏松活性的XW630由于其雌激素活性低,值得进一步研究。     

Effects of neonatal exposure to diethylstilbestrol on protein expression by vagina and uterus in mice.

Neonatal treatment of female mice with diethylstilbestrol (DES) results in genital tract abnormalities including ovary-independent vaginal proliferation and cornification. Protein profiles were examined in vagina and uterus from 45-day-old, ovariectomized C57BL/Tw mice which had been given 5 daily injections of 2 micrograms DES or oil vehicle alone from the day of birth, and in those from 45-day-old, ovariectomized mice given 3 daily injections of 0.1 microgram DES from 42 days of age. Proteins extracted were analyzed by two-dimensional polyacrylamide gel electrophoresis. In the vagina, expression of 37 non-keratin proteins was altered by postpubertal injections of DES as compared with the controls. In the neonatally DES-exposed vagina, expression of 26 of 37 proteins was altered as compared with controls. In the uterus, expression of 22 proteins was altered in the postpubertally DES-exposed group as compared with that in the control; however, the protein expression pattern of the neonatally DES-exposed group closely resembled that of the control except for one protein (no. 23, pI = 6.1, MW = 39.5 kDa) which was specifically increased in the neonatally DES-exposed group. By immunoblot analysis, 6 keratin polypeptides (49.5, 50, 52, 53, 57 and 58 kDa) were identified in vaginae of ovariectomized mice exposed neonatally and postpubertally to DES and of the controls. These results indicate that neonatal DES exposure induces organ specific alterations in the synthesis of proteins in mouse vagina and uterus.     

Effect of the estrous cycle on susceptibility of female mice to intravaginal inoculation of herpes simplex virus type 2 (HSV-2)

In order to explore the effect of sexual maturity on the susceptibility of mice to genital herpesvirus infections, mice were separated into the four stages of the estrous cycle and inoculated intravaginally with varying doses of HSV-2, strain 186. Deaths were observed as indicators of susceptibility and were recorded as follows: proestrous, 33%; estrous, 16%; metestrous, 9% and diestrous, 75%. To determine the course of infection in animals inoculated at different stages of estrous, cotton swabs were used to collect vaginal specimens at various times post-virus inoculation for virus titration. All mice inoculated during diestrous were positive for virus as early as 6 hours post-virus inoculation and had titers that increased over a 3 day period. Mice inoculated in other stages of estrus were positive only briefly (at 6 h) or had no detectable virus. In order to verify the susceptibility associated with diestrous, mice were ovariectomized to produce a continuous diestrous (pseudodiestrous) and when inoculated greater than or equal to 66.7% died. In contrast, none of the mice which had been ovariectomized and treated with estrogen to simulate the estrus stage died. We postulate that in stages other than diestrous virus may adsorb to epithelial cells in the lumen of the vagina and/or be expelled from the body by nonspecific resistance functions, thus reducing the likelihood of vaginal infection.     

雌三醇阴道栓剂对大,小鼠下生殖道作用的研究

以雌二醇（Ｅ＿２）阴道栓剂为阳性对照，雌三醇（Ｅ＿３）阴道栓剂对去卵巢大鼠阴道粘膜作用的效价为４．５８％；对去卵巢小鼠阴道粘膜作用的效价为２０．２７％；而对小鼠子宫增重作用的效价为３．４％，表明Ｅ＿３栓剂阴道给药对小鼠阴道粘膜作用较强而对子宫增重作用较弱。     

17β-雌二醇对卵巢切除小鼠海马内脑源性神经营养因子及神经营养因子 3表达的影响(英文)

目的　为确定雌激素可能具有的神经营养调节作用。方法　采用蛋白质印迹法检测上述指标的变化。结果　与卵巢未切除对照组相比 ,小鼠卵巢切除 10周后海马内脑源性神经营养因子 (BDNF)表达水平明显下降 ,给予 17β 雌二醇 (2 .4或 4 .8μg·d- 1,sc ,连续 12周 )替代具有明显的改善作用 (P <0 .0 1)。但卵巢切除及 17β 雌二醇替代对海马内神经营养因子 3表达水平无明显影响。结论　海马内BDNF表达水平的改变与雌激素缺乏具有密切关系。雌激素对调节海马内BDNF水平具有重要作用。     

Evaluation of the transplacental toxicity of diethylstilbestrol with the scanning electron microscope.

Exposure in utero to the synthetic estrogen diethylstilbestrol (DES) is associated with reproductive tract lesions in male and female CD-1 mice. The scanning electron microscope was used to evaluate the luminal surface of the vagina, cervix, and uterus following prenatal exposure to DES. Abnormalities that have been observed include urethral openings in the cervicovaginal area, squamous metaplasia of the uterus, glandular elements in the vagina, and abnormal cell surface features in the vaginal epithelium.     

Estradiol and pesticide methoxychlor do not exhibit additivity or synergism in the reproductive tract of adult ovariectomized mice

The pesticide methoxychlor (MXC) is a DDT substitute that exhibits estrogenic activities in different animals. To determine whether there is synergism between purified MXC and a natural estrogen, ovariectomized adult mice received 3 daily intraperitoneal doses of either 2.5 or 25 ng estradiol-17beta or 0.125, 0.25, or 0.5 mg MXC administered separately or in combination. The mice were sacrificed on d 4. Reproductive tracts were excised, weighed, and one uterine horn was flushed with phosphate-buffered saline, with the fluid electrophoresed on a one-dimensional sodium dodecyl sulfate polyacrylamide gel to determine albumin content. The remaining uterine horn and vagina were prepared for histology and epithelial height measurements. Estradiol significantly increased reproductive-tract weights. Although both the vaginal and uterine epithelial heights increased in mice treated with combined chemicals when compared to controls, the organ histology did not show increased stimulation. Albumin content was significantly elevated only in the estradiol group. The present data do not suggest that either synergism or additive effects occurred between an estrogen and MXC in the reproductive tracts of ovariectomized adult mice. In fact, combining MXC with estradiol suggests inhibitory effects.     

Estrogen receptor expression in the genital tract of female mice treated neonatally with diethylstilbestrol.

The distribution of the estrogen receptor (ER) was investigated immunohistochemically in the genital tract of 0 (day of birth)--to 50-day-old C57BL/Tw female mice given 5 daily injections of 2 micrograms diethylstilbestrol (DES) from the day of birth using an anti-ER monoclonal antibody. In the oviduct, cervix and vagina of control mice, both epithelial and stromal cell nuclei showed positive ER immunoreaction at 0 day. Nuclei of uterine stromal cells also showed strong ER immunostaining even at 0 day. In contrast, the ER in uterine epithelial cells began to appear by day 5. The number of positive epithelial cells and staining intensity gradually increased until 10 days. In neonatally DES-exposed mice, ER appeared in uterine epithelial cells 24 h after the injection. Polygonal cells appearing in the vaginal epithelium of DES-exposed 3-day-old mice showed weak ER staining. Neonatal DES exposure reduced staining intensity of columnar vaginal epithelial cells and uterine stromal cells at 3 days. Vaginal epithelial cells undergoing ovary-independent stratification and cornification in neonatally DES-exposed mice and normal estrous mice showed ER immunoreaction only in the basal cells.     

Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice

Proliferation and differentiation of cells in female reproductive organs, the oviduct, uterus and vagina, are regulated by endogenous estrogen. In utero exposure to a synthetic estrogen, diethylstilbestrol (DES), induces vaginal clear-cell adenocarcinoma in humans. In mice, perinatal exposure to DES results in abnormalities such as polyovular follicles, uterine circular muscle disorganization and persistent vaginal epithelial cell proliferation. We reported the persistent gene expression change such as interleukin-1 (IL-1) related genes, insulin-like growth factor-I (IGF-I) and its downstream signaling in the mouse vagina exposed neonatally to DES. In this study, we found persistent up-regulation of Wnt4 and persistent down-regulation of Wnt11 in the vagina of mice exposed neonatally to DES and estrogen receptor α specific ligand. Also Wnt4 expression in vagina is correlated to the stratification of epithelial cells with the superficial keratinization of vagina, but not epithelial cell stratification only.     

香椿叶总黄酮对糖尿病小鼠血糖的影响

目的研究香椿叶总黄酮对糖尿病小鼠血糖的影响。方法采用链脲佐菌素腹腔注射制备糖尿病小鼠模型,造模成功小鼠随机分为模型组、香椿叶总黄酮大剂量(800 mg·kg-1·d-1)、中剂量(400 mg·kg-1·d-1)和小剂量组(100 mg·kg-1·d-1),优降糖组(60mg·kg-1·d-1),连续给药30 d后,观察血糖的变化。结果香椿总黄酮可明显降低糖尿病小鼠的血糖。结论香椿叶总黄酮有明显的降糖作用,为临床上防治糖尿病提供了理论依据。     

还原型谷胱甘肽与多烯磷脂酰胆碱对环磷酰胺诱导小鼠肝损伤的修复作用

目的：分析比较还原型谷胱甘肽与多烯磷脂酰胆碱对环磷酰胺诱导小鼠肝损伤的防护作用。方法采用简单随机抽样法将40只昆明小鼠分为肝损伤模型组、还原型谷胱甘肽组、多烯磷脂酰胆碱组和对照组,每组10只。前3组小鼠实验第1-4天均腹腔注射环磷酰胺（100 mg· kg-1·d-1）诱导肝损伤,第5-14天分别腹腔注射0.9%氯化钠注射液0.2 ml、还原型谷胱甘肽180 mg · kg-1· d-1、多烯磷脂酰胆碱90 mg·kg-1·d-1;对照组同期腹腔注射等体积0.9%氯化钠注射液。实验第1天给药前和第15天测定小鼠体重;实验第15天,小鼠处死前眼眶取血测定血清总胆红素和谷胱甘肽水平,处死小鼠后取肝脏称重并计算肝脏系数,取肝组织测定丙氨酸转氨酶（ ALT）、天冬氨酸转氨酶（AST）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性和丙二醛（MDA）水平,并进行肝组织形态学观察。结果实验第15天,应用环磷酰胺的3组小鼠体重均明显低于对照组（P 〈0.01或 P 〈0.05）,但还原型谷胱甘肽组体重高于肝损伤模型组（P 〈0.05）;肝损伤模型组小鼠肝脏系数（5.74%±0.11%）高于对照组（4.68%±0.37%）和还原型谷胱甘肽组（4.81%±0.19%）（均 P 〈0.01）,多烯磷脂酰胆碱组小鼠肝脏系数（5.25%±0.35%）]也高于对照组（P 〈0.05）。肝损伤模型组、还原型谷胱甘肽组、多烯磷脂酰胆碱组血清总胆红素水平[（129.8±1.9）、（110.9±1.3）、（125.7±2.6）μmol/ L]均高于对照组（100.8±3.0）μmol/ L（均 P 〈0.01）,但还原型谷胱甘肽组低于肝损伤模型组（P 〈0.01）。肝损伤模型组和多烯磷脂酰胆碱组血清谷胱甘肽水平[（50.5±1.9）、（55.9±2.4）g/ L]均低于对照组和还原型谷胱甘肽组[（73.8±4.3）、（71.3±3.7）g/ L]（均 P 〈0.01）。肝损伤模型组、还原型谷胱甘肽组、多烯磷脂酰胆碱组肝组织 AST、ALT、SOD 和 CAT ?