长效孕激素炔诺酮庚酸酯及复方18甲基炔诺酮对血清性激素结合球蛋白的影响

24例妇女肌注炔诺酮庚酸酯200 mg,肌注前血清性激素结合球蛋白(SHBG)为53.32±23.23 nmol╱L。注射后5天为41.99±17.06nmol/L(P<0.05),21天降至最低值14.72±10.01 nmol/L,以后逐渐回升,直至注射后84天仍未回复到原来水平(34.46±20.39 nmol/L)。10例妇女单次口服18甲基炔诺酮6 mg+炔雌醚3 mg,服药前血清SHBG水平为42.76±13.89 n mol/L,服药后7天为62.53±10.90 nmol/L(P<0.01),14天达峰值为71.33±5.77 nmol/L,以后持续此高水平,直至服药后56天;8例连续3次口服18甲+炔雌醚,每次间隔23天,服药前血清SHBG水平为44.94±15.36 nmol/L,第1次服药后9天为83.46±10.08 nmol/L(P<0.01),16天达峰值为91.74±2.28nmol/L,以后持续高水平直至第3次服药后30天,第2、3次重复给药对业已升高的SHBG水平无影明显响。第2、3次服药后LNG峰值明显高于首次服药后峰值6倍。     

甲状腺功能减退症与勃起功能障碍关系的初步探讨

甲状腺功能减退(HT)即甲状腺激素分泌不足的状态下,脂质代谢紊乱产生的高脂血症、血管内皮细胞功能障碍、血管平滑肌细胞舒张性下降等均可影响阴茎勃起功能。NO、CO、H2S及内皮素等在HT中起着重要作用。通过对高脂血症、高血糖、心血管病变的治疗及补充睾酮等,可明显改善阴茎勃起功能,因而积极治疗HT,对改善HT所致阴茎勃起功能障碍(ED)具有重要意义。内皮功能障碍被认为是ED的主要发病机制,因此治疗HT时同时改善内皮功能,也会对ED发挥治疗作用。同时HT引起的神经损伤也参与了ED。通过对这些物质、神经及其功能的深入研究,可为今后临床上治疗ED提供理论依据。     

Polycystic ovary syndrome and the single nucleotide polymorphisms of methylenetetrahydrofolate reductase: a pilot observational study

Polycystic ovary syndrome (PCOS), insulin resistance and overall mortality due to diabetes and coronary artery disease are higher in South Asians than in Caucasians. Aims: We compared the prevalence of the C677T and A1298C single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene in South Asian and Caucasian women, its association with folate and homocysteine (Hcy) metabolism, and its relevance to future atherogenic events. Methods and results: 71 women were recruited for the study: South Asian PCOS (21) plus controls (9) and Caucasian PCOS (25) plus controls (16). Anthropometric and laboratory parameters were compared. South Asian PCOS women were significantly hyperandrogenic and exhibited a greater degree of insulin resistance. Caucasian PCOS women had higher plasma Hcy concentrations with a 1.9 times higher frequency of the T allele than the South Asian PCOS group. In the presence of this variant allele, plasma Hcy levels appear to be higher in both PCOS groups. The South Asians had a 1.8 times higher frequency of the C allele than the Caucasians; however, the overall frequency was comparable in the two PCOS groups. The frequency of homozygosity, i.e. TT677 and CC1298, was 7.2% and 4.9% in the Caucasians and 0% and 16.6% in the South Asian recruits, respectively.

Dietary inadequacies in the South Asian women can influence their plasma folate and B12 concentrations resulting in hyperhomocysteinemia which, in combination with dyslipidaemia and insulin resistance, can lead to long-term atherogenic consequences. Conclusions: Current data suggests that the mechanisms of atherothrombosis have separate pathways in the two ethnic groups. Larger studies exploring the current theme need to be carried out in the PCOS groups to obtain adequate insight.     

鸟氨酸脱羧酶对人滋养细胞分泌绒毛膜促性腺激素的调控作用

本实验应用无血清短周期培养方法，研究了人滋养层细胞（ＣＴＣ）分泌ｈＣＧ的调节机制。实验发现：ＣＴＣ经８ｈ培养具有良好的ｈＣＧ分泌功能。这些细胞的匀浆液具有鸟氨酸脱羧酶（ＯＤＣ）的活性，而且对二丁酰ｃＡＭＰ、多胺、放线菌素Ｄ和二氟甲基鸟氨酸（ＤＦ－ＭＯ）呈现不同的应答效应。ＯＤＣ的活性与ＣＴＣ的数量及各试剂的剂量都有密切的相关性。ＯＤＣ活性的改变又与细胞分泌ｈＣＧ功能有关。它们在ＣＴＣ分泌的调控中可能是一个重要的因素．     

新型左炔诺孕酮/炔雌醇复方避孕贴剂的家兔药代动力学研究

目的:探讨新型左炔诺孕酮(levonorgestrel,LNG)和炔雌醇(ethynylestradiol,EE)在家兔体内的药物动力学特征,评价多次给药后是否出现药物蓄积情况。方法:家兔在单次和多次给药及停止给药后不同时间点耳缘静脉采血,选择放射免疫分析(radioimmunoassay,RIA)法测定各时间点各组家兔雌/孕激素的血药浓度,使用药物动力学软件计算各药物动力学参数并对其进行统计分析。结果:单次给药后受试贴剂低(10cm2)、中(20 cm2)和高剂量(40 cm2)组血清LNG峰浓度(Cmax)分别为1.04±0.12 ng/ml、2.42±0.60 ng/ml和4.90±1.39 ng/ml,3组间有显著差异(P<0.05)。血药浓度-时间曲线下面积(AUC)分别为49.93±9.79h.ng/ml、115.14±34.25 h.ng/ml和251.22±80.55 h.ng/ml,3组间有显著差异(P<0.01);血清EE峰浓度(Cmax)分别为112.00±45.50 pg/ml、139.23±28.23 pg/ml和290.26±66.62 pg/ml,中、高剂量组间有显著差异(P<0.05),而中、低剂量组间无统计学差异(P>0.05)。EE血药浓度-时间曲线下面积(AUC)分别为4.70±1.34 h.ng/ml、6.59±1.23h.ng/ml和16.59±2.33 h.ng/ml,中、高剂量组之间有显著差异(P<0.01)。Evra参比避孕贴剂组血清LNG浓度的Cmax为3.16±1.00 ng/ml,AUC为155.29±46.14 h.ng/ml,与LNG/EE避孕贴剂中剂量组(拟采用的临床试验剂量)相比,两者无显著差异(P>0.05)。中剂量组血清EE浓度与Evra避孕贴剂的相比显著降低(P<0.05)。多次给药后LNG/EE避孕贴剂10 cm2组和20 cm2组在重复给药10次的过程中未出现LNG和EE血药浓度蓄积现象,Evra贴剂组在重复给药4次的过程中未出现LNG和EE血药浓度蓄积现象。结论:中剂量的LNG/EE避孕贴剂具有良好的避孕效果,同时其副作用可能小于Evra。     

Associations between toxic metals in follicular fluid and in vitro fertilization (IVF) outcomes

Purpose

We previously reported associations between trace concentrations of Hg, Cd and Pb in blood and urine and reproductive outcomes for women undergoing in-vitro fertilization (IVF). Here we assess measurements in single follicular fluid (FF) specimens from 46 women as a presumably more relevant marker of dose for reproductive toxicity.

Methods

FF specimens were analyzed for Hg, Cd and Pb using sector field-inductively coupled plasma-mass spectrometry (SF-ICP-MS). Variability sources were assessed by nested ANOVA. Multivariable regression was used to evaluate associations for square root transformed metals with IVF outcomes, adjusting for confounders.

Results

An inverse association is detected for FF Pb and fertilization (relative risk (RR) = 0.68, P = 0.026), although positive for Cd (RR = 9.05, P = 0.025). While no other statistically significant associations are detected, odds ratios (OR) are increased for embryo cleavage with Hg (OR = 3.83, P = 0.264) and Cd (OR = 3.18, P = 0.644), and for embryo fragmentation with Cd (OR = 4.08, P = 0.586) and Pb (OR = 2.22, P = 0.220). Positive estimates are observed for Cd with biochemical (RR = 19.02, P = 0.286) and clinical pregnancies (RR = 38.80, P = 0.212), yet with very low precision.

Conclusions

We have identified associations between trace amounts of Pb and Cd in FF from a single follicle, and oocyte fertilization. Yet, the likelihood of biological variation in trace element concentrations within and between follicles, coupled with levels that are near the limits of detection suggest that future work should examine multiple follicles using a ‘one follicle-one oocyte/embryo’ approach. A larger study is merited to assess more definitively the role that these environmental factors could play with respect to egg quality in IVF programs.     

取卵日血清脑源性神经营养因子与辅助生育结局的相关性

目的:探讨取卵日血中脑源性神经营养因子(BDNF)能否预测卵母细胞质量和其后的卵胞质内单精子注射(ICSI)的妊娠结局。方法:总共纳入57例进行ICSI患者,在取卵日清晨抽取空腹静脉血,测量BDNF,E2和P的浓度。比较妊娠组与非妊娠组的相关数据,并分析取卵日BDNF水平与E2、P、年龄和IVF相关数据之间的相关性。结果:妊娠组与非妊娠组的BNDF浓度无明显差异;取卵日BDNF浓度与E2和P呈明显正相关。BDNF与获卵数和成熟卵母细胞数成正相关。结论:尚不能用取卵日BDNF来预测ICSI的妊娠结局,但BDNF可能在卵母细胞发育成熟过程中发挥着重要作用。     

促性腺激素释放激素激动剂联合曼月乐治疗保守性手术后中重度子宫内膜异位症的疗效分析

目的:探讨促性腺激素释放激素激动剂(GnRHa)联合曼月乐治疗中重度子宫内膜异位症(EMs)保守性手术后的疗效。方法:选择腹腔镜保守性手术后中重度EMs、无生育要求的患者43例,随机分为2组,试验组23例,术后使用GnRHa联合曼月乐治疗,对照组20例,术后单纯使用GnRHa治疗。随访12个月,比较手术前、手术后3个月、6个月、9个月和12个月疼痛评分、CA125值和复发率。结果:试验组和对照组中,术后各时间点的疼痛评分均低于术前(P<0.05);试验组中术后各时间点的疼痛评分无统计学差异;对照组中术后12个月疼痛评分均高于术后3个月、6个月和9个月(P<0.05);在术后12个月试验组的疼痛评分低于对照组(P<0.05)。试验组和对照组中,术后各时间点CA125值均低于术前(P<0.05);试验组中术后各时间点CA125值无统计学差异。对照组中术后12个月CA125值均显著高于术后3个月、6个月和9个月(P<0.05)。术后12个月试验组的CA125低于对照组(P<0.05)。试验组的复发率为0.0%;对照组的复发率为15.0%。结论:GnRHa联合曼月乐治疗保守性手术后中、重度EMs,可以长时间缓解疼痛,降低术后复发率,是一种有效的巩固治疗方法。     

非编码RNA在卵泡发育和卵巢疾病中的研究进展

非编码RNA(non-coding RNA,nc RNA)是目前生物医学领域的研究热点,如长链非编码RNA(long non-coding RNA,lnc RNA)和小非编码RNA:微小RNA(mirco RNA,mi RNA)、内源性小干扰RNA(endogenous small interfering RNA,endo-si RNA)、PIWI相互作用RNA(PIWI interacting RNA,pi RNA)等,它们作为细胞内基因调控网络的重要成员影响细胞的各种生命活动。近年来研究表明这些非编码RNA在卵巢也发挥重要作用,参与了颗粒细胞增殖、分化、凋亡以及激素合成的调控,在卵母细胞存活和发育中发挥重要作用,非编码RNA的表达异常与多囊卵巢等疾病密切相关,本文就非编码RNA与卵巢卵泡发育以及卵巢相关疾病的研究作一简述。     

Persistent increase of PRL after oral contraceptive treatment

 Background: The mechanism involved in estrogen induced hyperprolactinemia is not completely known, although one of the possible theories suggest inhibition of dopaminergic tone. Our objective was to study the mechanism implied in the increment of PRL levels as a consequence of oral contraceptive treatment and possible modifications in TSH levels. Material and methods: We performed a trial on 21 healthy women, nulliparas. We administered 35 μg of Etinil-Estradiol (EE) and 2 mg of Ciproterone Acetate (CA) for a period of 12 months. Stimulation tests with Metoclopramide and TRH were carried out before treatment, after 3, 6 and 12 months of treatment and finally 6 months after cessation of treatment. Results. Basal levels of PRL (×–₁=12.62 ng/ml) increased significantly (p<0.05) during the year of treatment (×–₁₂=17.04 ng/ml) and maintained higher levels 6 months after cessation (×–₁₈=17.53 ng/ml). Maximum values obtained in response to metoclopramide (×–₁=154.78) were significantly higher after 12 months (×–₁₂=173.29), persisting 6 months after cessation of treatment (×–₁₈=245.28). We also observed significant differences in the maximum response of TSH to metoclopramide during the same period of study (×–₆=2.45), (×–₁₂=2.76) and (×–₁₈=2.07) respectively (p<0.05). We did not find changes in PRL and TSH responses to TRH stimulation after a year of treatment with EE and CA. Conclusion: Treatment with EE (35 μg) and CA (2 mg) induces an increase in PRL levels that persist 6 months after cessation of treatment. Our results rule out the possibility that this increase in PRL is due to a decrease in dopaminergic tone or an increase in TRH sensitivity. Received: January 1999 / Accepted: 4 May 1999     

40例输精管道梗阻性无精子症诊疗策略分析

目的:探讨输精管道梗阻性无精子症(OA)的诊疗策略。方法:40例输精管道OA患者为研究对象。首先行输精管道探查,根据术中探查情况行输精管-输精管显微吻合术(VV)、输精管-附睾显微吻合术(VE)、交叉输精管-输精管吻合术、交叉输精管-附睾管显微吻合术或睾丸取精冻存术。结果:精道探查后,共行吻合手术26例,取精+冻精手术14例。40例患者中,共有3例患者失访(2例吻合患者,1例冻精患者)。随访到的24例吻合术患者术后复通率为58.3%(14/24),自然受孕率为29.1%(7/24)。随访到的13例取精+冻精患者中已有11例行ICSI/冻精助孕。结论:输精管道OA,可根据术前严格评估和术中探查行显微复通手术或取精术;复通术后可获得自然妊娠的机会,交叉显微吻合为输精管道复通的有效途径之一。     

牡蛎提取物拮抗维甲酸致小鼠神经管畸形的实验研究

目的:探讨维甲酸(RA)致神经管缺陷畸形(NTDs)的分子机理及牡蛎提取物的拮抗作用。方法:用RA建立小鼠胚胎NTDs模型,分析比较RA组、不同剂量的牡蛎保护组与各自对照组鼠胚神经管发育情况;用免疫组织化学方法和图像分析技术,对各组鼠胚的神经上皮细胞缝隙链接蛋白43(Cx43蛋白)的表达进行定性、定位和半定量观察。结果:①空白对照组和牡蛎对照组鼠胚中未见吸收胎、死胎及畸胎,神经管发育良好,Cx43蛋白定位于神经上皮细胞的细胞膜和细胞质,组间阳性表达情况比较无显著性差异(P>0.05);②RA组鼠胚吸收胎(27.2%)、死胎(5.8%)和畸胎(47.6%)发生率最高,其神经管发育不良、闭合不全,Cx43蛋白呈强阳性表达;③牡蛎高剂量组鼠胚中的吸收胎(11.6%)、死胎(3.9%)及畸胎(16.5%)均明显低于RA组(P<0.05),鼠胚神经管发育良好,与RA组比较,神经上皮中Cx43蛋白的表达显著降低(P<0.05)。结论:①Cx43蛋白的过度表达可能是RA诱导NTDs的机理之一;②牡蛎可以通过改善Cx43基因的表达而拮抗RA对胎鼠的致畸作用。     

多囊卵巢综合征患者脂联素、C反应蛋白水平的变化及其意义

目的:探讨脂联素(APN)、C反应蛋白(CRP)的变化对多囊卵巢综合征(PCOS)发病的意义。方法:按体重指数(BMI≥25kg/m2或<25kg/m2)分别将PCOS患者52例、对照组47例分为PCOS肥胖组(25例)、非肥胖组(27例)和对照肥胖组(23例)、对照非肥胖组(24例)4组。用ELISA法测定4组的APN水平、散射比浊法测CRP水平,葡萄糖氧化酶法测定空腹血糖(FPG)、化学发光法测空腹胰岛素(FIN)水平,并计算胰岛素抵抗指数(HOMA-IR)。结果:①PCOS组APN水平低于对照组(P<0.05),且同组肥胖者低于非肥胖者。②PCOS组CRP水平高于对照组(P<0.05),且肥胖者高于非肥胖者。③APN水平与BMI、HOMA-IR水平呈明显负相关(P<0.05)。结论:PCOS组APN水平降低,CRP水平升高,且以肥胖者明显。APN水平降低、CRP水平升高与PCOS患者胰岛素抵抗密切相关。     

细菌脂多糖对小鼠生长发育和骨骼发育的影响

目的:研究细菌脂多糖(LPS)对小鼠宫内胎儿死亡(IUFD)、生长发育迟缓(IUGR)和骨骼发育迟缓的影响。方法:LPS低中高组小鼠于妊娠d15-17分别腹腔注射不同剂量LPS(25μg/kg、50μg/kg、75μg/kg),LPS+2-苯叔丁基硝酮(PBN,活性氧ROS拮抗剂)组在LPS(75μg/kg)处理前30min和后3h经腹腔各给予100mg/kg的PBN,对照组给予等容量生理盐水。孕鼠于妊娠d18处死。另给药1d时取LPS高剂量组LPS+PBN组和对照组于LPS处理后6h处死孕鼠。结果:①小鼠妊娠d15-17给予LPS后,中高剂量组平均每窝死胎数明显高于对照组,活胎体重、身长和尾长下降,并呈明显的剂量-效应关系;LPS高剂量导致IUGR和骨骼发育迟缓;PBN处理明显抑制LPS对胎儿的作用。②LPS使母肝、胎肝和胎盘组织脂质过氧化,GSH含量显著降低。PBN显著抑制LPS的这些作用。结论:母鼠妊娠晚期接触LPS引起IUFD、IUGR和骨骼发育迟缓,ROS至少部分参与了LPS的引起IUFD、IUGR和骨骼发育迟缓。     

hMG对分泌晚期子宫内膜雌、孕激素受体基因表达的影响

目的:研究人绝经期促性腺激素(hMG)促排卵治疗对分泌晚期子宫内膜雌激素受体(ER)、孕激素受体(PR)基因表达的影响。方法:采用原位杂交技术,对9例hMG促排卵周期(实验组)分泌晚期子宫内膜ER、PRmRNA进行测定,并与11例自然周期(对照组)进行对照研究。结果:实验组分泌晚期子宫内膜腺体细胞内ER、PRmRNA水平明显低于对照组(P<0.05和P<0.005)。结论:hMG在转录水平降低分泌晚期子宫内膜腺体细胞ER、PRmRNA的表达。