外源性雌激素苯甲酸雌二醇对青春期前雄性大鼠生殖系统的影响

目的 观察外源性雌激素对青春期前雄性大鼠生殖系统的影响。 方法 将45只大鼠随机分为用高、低剂量组和对照组,苯甲酸雌二醇(E2B)染毒剂量分别为15 000 μg/kg、15 μg/kg,0 μg/kg灌胃摄入,对照组给予同等体积玉米油,隔日1次,在分别作用3个周后正常饲养至生后9周,处死取材,测定相应指标。结果 与对照组相比,低剂量组睾酮(testosterone,T)浓度降低(P<0.05),卵泡刺激素(follicle-stimulating hormone,FSH)、黄体生成素(luteinizing hormone,LH)及雌二醇(estrodiol,E2)浓度升高,差异均有统计学意义(P<0.01)。高剂量组4种激素水平改变更显著(P<0.01)。另外,两实验组相比,T、FSH、LH及E2浓度的差异也有统计学意义(P<0.05)。两实验组睾丸生殖小管、肛生殖距(AGD)均有异常改变,高剂量组改变较低剂量组明显。 结论外源性雌激素可改变青春期前雄性大鼠血清性激素水平,并使生殖小管的正常结构和形态发生异常改变。     

SPERM DNA FRAGMENTATION IS INCREASED IN COUPLES WITH UNEXPLAINED RECURRENT PREGNANCY LOSS

Previous studies have indicated that sperm quality may be related to unexplained recurrent pregnancy loss. This study evaluated the degree of sperm DNA fragmentation using the TUNEL assay on sperm from 24 couples with unexplained recurrent pregnancy loss (RPL) compared to sperm from 2 control groups: donors of known fertility and unscreened men from the general population. The percentage of sperm staining positive for DNA fragmentation was increased ( p <.001) in the RPL group (38±4.2) compared to the donor (11.9±1.0) or general population (22±2.0) control groups. In the RPL group, no correlation was observed between semen quality parameters and the TUNEL data. These data indicate that some RPL patients have a significant increase of sperm DNA fragmentation, which may be causative of pregnancy loss in some patients.     

Pharmacokinetics of medroxyprogesterone acetate after single and multiple injection of cyclofem® in Chinese women

To provide pharmacokinetic data for safety evaluation on prolonged treatment with Cyclofem®, which contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate in 0.5 mL microcrystalline aqueous suspension, the pharmacokinetic profiles of MPA after single and multiple administration of this monthly injectable contraceptive were investigated in Chinese women. Nine healthy fertile women received Cyclofem based on a once-a-month regimen for up to 1 year. Blood samples were collected immediately prior to drug administration and on days 1, 3, 5, 7, 14, 21, and 28 after injection. After the 1st, 6th, and 12th injection, the maximum serum concentrations (C_max) of MPA were observed on days 3.4 ± 0.9, 4.3 ± 2.2, and 3.7 ± 2.6, respectively. C_max of serum MPA during the 1st, 6th, and 12th treatment cycles were 3.75 ± 1.27, 5.54 ± 1.79, and 5.55 ± 1.80 nmol/L, whereas the areas under the curve (AUC_{0–28 days}) were 55.84 ± 28.15, 95.45 ± 26.56, and 98.81 ± 21.84 nmol/L·day, respectively. There was significant interindividual variation in the pharmacokinetics of MPA after intramuscular injection of Cyclofem. No significant change was demonstrated in mean residence time (MRT) of MPA after single and multiple injection. There was a tendency of increase in C_max and AUC_{0–28 days} of MPA during the first 6 months of treatment, whereas no further enhancement was found between the 6th and 12th injection (p > 0.05). Peak levels of estradiol (E₂) observed in Cyclofem users were within the normal range of the preovulatory phase. Results of this long-term study suggest that no drug accumulation occurred after repeated administration of Cyclofem in the Chinese women.     

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。     

Effect of clofibrate administration on the esterification and deesterification of steroid hormones by liver and extrahepatic tissues in rats

Treatment of rats with clofibrate markedly stimulated the liver microsomal esterification of estradiol, testosterone, pregnenolone, dehydroepiandrosterone, and corticosterone by acyl-CoA:steroid acyltransferase. This enzyme catalyzes the esterification of estradiol with long-chain fatty acids in both liver and extrahepatic tissues. In untreated control rats, brain had the highest acyltransferase activity per milligram of microsomal protein for estradiol esterification (3- to 4-fold higher than in the liver). Although, treatment of rats with clofibrate stimulated the esterification of estradiol by 9- to 14-fold in the liver, estradiol esterification in kidney, lung, brain, uterus, fat, and mammary glands was not increased, indicating that liver may be uniquely sensitive to induction of acyl-CoA:estradiol acyltransferase by clofibrate. In additional studies, esterase activity for hydrolysis of the oleoyl ester of estradiol was determined in control and clofibrate-treated rats. Clofibrate administration increased esterase activity by an average of 107% in fat and 70% in liver. The results indicate that treatment of rats with clofibrate stimulates the hepatic formation of highly lipophilic fatty acid esters that can be hydrolyzed in the liver and in extrahepatic tissues to the parent steroid hormone by a clofibrate-inducible esterase.     

Intrauterine bisphenol A exposure leads to stimulatory effects on Sertoli cell number in rats

Using the optical disector for quantifying cell numbers, we investigated whether oral treatment of rats on days 6-21 of gestation with the weakly estrogenic bisphenol A (BPA, 0.1 or 50 mg/kg) or the highly estrogenic ethinyl estradiol (EE, 0.02 mg/kg) alters testicular histology, in those offspring 9-12 month of age. Since production of male germ cells depends on Sertoli cell number, possible changes in that parameter were investigated using unbiased stereology. Spermatogenesis was qualitatively normal in all groups. BPA increases Sertoli cell number per organ but not when expressed as per gram testis. EE did not affect cell number per organ but did affect numbers on a per gram testis basis due to a lowered testis weight. In contrast to the lowering of Sertoli cell numbers that might have been expected according to the estrogen hypothesis, intrauterine administration of these xenoestrogens in fact resulted in minor increases in Sertoli cell numbers and had no qualitative effect on spermatogenesis.     

SLE发病机制中雌激素与细胞因子之间的关系

目的：探讨系统性红斑狼疮（SLE）外周血单个核细胞（PBMC）经雌二醇（E2）刺激前后TNFα和IL-6水平变化的相关性。方法：提取SLE患者（患者组）及健康志愿者（对照组）的PBMC，用酶联免疫吸附法（ELISA）测定上清液在E2刺激前后的肿瘤坏死因子α（TNFα）和白细胞介素6（IL-6）水平。结果：患者组有或无E2刺激的PBMC分泌的TNFα水平均高于对照组（P〈0．01），患者组E2刺激后PBMC分泌的TNFα水平低于无E2刺激时（P〈0．05），而对照组E2刺激前后TNFα水平无明显变化（P〉0．05）。无E2刺激的PBMC分泌的IL-6水平患者组高于对照组（P〈0．05），患者组有E2刺激PBMC分泌的IL-6水平与对照组比较差别无统计学意义（P〉0．05）。2组PBMC在E2刺激后分泌的IL-6水平均降低（均P〈0．05）。结论：TNFα和IL-6水平可以作为SLE疾病活动的监测指标，高水平的E2对SLE的PBMC分泌TNFα和IL-6都有明显抑制作用。TNFα的降低可能提示为SLE活动期。     

消乳散结胶囊联合他莫昔芬治疗乳腺增生症的疗效观察

目的 研究瑞香狼毒Stellera chamaejasme花中黄酮和木脂素类化学成分及其抗氧化活性,分析构效关系。方法 利用大孔吸附树脂、正反相硅胶、Sephadex LH-20等色谱分离材料,通过柱色谱和高效液相色谱等分离方法进行分离纯化,运用核磁共振（NMR）、质谱（MS）等波谱技术鉴定化合物结构,并采用FRAP法、DPPH法和ABTS法对分离得到的化合物进行体外抗氧化活性测试。结果 从瑞香狼毒花甲醇提取物中分离鉴定了12个化合物,分别鉴定为艾黄素（1）、槲皮素（2）、isoscutellarein-8-O-β-D-glucuronopyranoside（3）、槲皮素-3-O-β-D-葡萄糖苷（4）、紫云英苷（5）、hypolaetin-8-O-β-D-glucuronopyranoside（6）、kaempferol 3-O-β-D-glucopyranosyl-（1→2）-O-α-L-xylopyranoside（7）、rel-（3R,3''S,4R,4''S）-3,3'',4,4''-tetrahydro-6,6''-dimethoxy[3,3''-bi-2H-benzopyran]-4,4''-diol（8）、马台树脂醇（9）、乌拉尔醇（10）、环黄芪醇（11）、松脂醇（12）。抗氧化活性实验表明,黄酮和木脂素类化合物均显示了较强的抗氧化活性。结论 化合物1、3、5～7和10为首次从该植物中分离得到;化合物2、4、5和10表现出显著的抗氧化活性,其中黄酮类化合物C-3或C-8位连有糖链会降低其抗氧化活性。     

基于计算生物学方法的小容量单域抗体库的构建及食品中雌二醇特异性抗体的筛选

目的构建骆驼源单域抗体实体库和虚拟库,为快速筛选检测食品中小分子污染物的特异性抗体提供新方法。方法通过基因克隆、一代测序、同源性分析的方法构建骆驼源单域抗体基因库,通过二级结构分析和同源建模的方法建立单域抗体的三维结构虚拟库,利用分子对接技术实现雌二醇特异性抗体的虚拟筛选,并以雌二醇小分子为靶标进行初步验证。结果构建的小容量单域抗体库含有2000株抗体,每一株抗体的遗传背景、蛋白质结构及抗体抗原互补决定区(CDR)的信息清晰;通过分子对接得到结合雌二醇小分子能力最高的一株抗体的半经验结合自由能绝对值为9.56;相互作用分析结果显示,单域抗体结构中和雌二醇小分子发生相互作用的主要为3个CDR区形成的loop结构,经间接ELISA验证,其和雌二醇结合的50%抑制率(IC50)值为20 ng/ml,检测限(LOD,IC10)为4.097 ng/ml。结论通过计算生物学和基因工程技术相结合的方法构建的骆驼源单域抗体库,针对食品中常见的激素类兽药雌二醇,可以筛选得到背景清晰、具有较高亲和力的特异性抗体。     

CA125、孕酮联合雌二醇预测先兆流产的价值

目的 探讨血清癌抗原125（CA125）、孕酮联合雌二醇预测先兆流产的临床价值。方法 回顾性分析2012年3月至2014年3月解放军第一零一医院收治的孕龄在6～8周的单胎孕妇,按照妊娠结局将其分为3组：先兆流产组、难免流产组以及正常妊娠组,分别测定三组的CA125、孕酮以及雌二醇水平。结果 3组的CA125、孕酮、雌二醇经方差分析比较,差异均有统计学意义（F值分别为15．731、3．608、26．253,均P＜0．05）,两两比较后发现正常妊娠组的CA125显著低于先兆流产组和难免流产组（t 值分别为12．183、16．065,均P＜0．05）,先兆流产组的CA125低于难免流产组（t＝9．187,P＜0．05）,正常妊娠组的孕酮、雌二醇显著高于先兆流产组和难免流产组（t值分别为10．073、12．685、9．936、18．187,均P＜0．05）,先兆流产组孕酮、雌二醇显著高于难免流产组（t值分别为9．637、10．098,P＜0．05）。 CA125、孕酮、雌二醇检测的灵敏度、特异度、准确性差异无统计学意义（χ^2分别为1．962、1．734、0．985,P＞0．05）,CA125、孕酮联合雌二醇对先兆流产患者预后的灵敏度、特异度、准确性均显著高于其它三组（χ^2分别为5．184、6．861、4．086,均P＜0．05）。结论 CA125、孕酮联合雌二醇对先兆流产进行预测具有准确性高的特点,临床有重要参考价值。