替勃龙对卵巢切除大鼠膀胱功能及结构的影响

目的:通过比较正常、卵巢切除及卵巢切除后补充替勃龙大鼠的膀胱功能和组织形态,探讨替勃龙对膀胱的影响及其作用机制。方法:30只雌性成年SD大鼠分为3组:正常对照组、切除双侧卵巢组(OVX组)、切除双侧卵巢后补充替勃龙组(OVX+Tib组)。用药12周后测定膀胱压力容积,Masson染色膀胱石蜡切片分析胶原纤维(CF)和平滑肌(SM)的面密度及二者比值。结果:(1)OVX组膀胱最大容量(0.32±0.20m l)、顺应性(0.012±0.006m l/cmH2O)和最大收缩力(1.4±0.4cmH2O)相对于正常对照组(分别为1.11±0.09m l、0.026±0.003m l/cmH2O和4.4±0.3cmH2O)明显减少,有统计学差异(P<0.01)。OVX+Tib组膀胱顺应性(0.022±0.003m l/cmH2O)与正常对照组比较无统计学差异(P>0.05),膀胱最大容量(0.87±0.26m l)及最大收缩力(3.3±1.0cmH2O)比正常对照组减少(P<0.05),但比OVX组增加(P<0.01);(2)CF面密度、CF面密度与SM面密度比值:OVX组(0.2180±0.0407和0.5396±0.0837)比正常对照组(0.1598±0.0387、0.3199±0.0860)增加,有统计学差异(P<0.01)。OVX+Tib组此两值(0.1893±0.0251、0.4249±0.0646)介于OVX组与正常对照组之间。结论:大鼠切除双侧卵巢后膀胱功能降低,补充替勃龙在一定程度上改善了膀胱功能,这可能是与它对胶原的抑制有关。     

替勃龙对绝经妇女血浆一氧化氮含量的作用

为观察替勃龙(tebolone)对一氧化氮(NO)含量的影响进行随机对照对照试验。收集18例健康绝经后妇女,随机9例服用替勃龙(A组),平均年龄52.4岁,另9例服安慰剂(B组),平均年龄50.8岁。患者绝经时间至少1年,不超过4年。体重均在正常范围(体重指数≤25),不吸烟,未服用药物和激素,具有适合自身年龄的生活习惯和体能活动。无潮红症     

替勃龙上调卵巢切除大鼠腰椎护骨素mRNA的表达

目的:建立绝经后骨质疏松(postmenopausalosteoporosis,PMOP)的大鼠模型,研究替勃龙对卵巢切除大鼠腰椎组织中护骨素(OPG)基因mRNA表达水平的影响,探讨其预防和治疗PMOP的作用机制。方法:6月龄未交配健康雌性SD大鼠40只,随机分为SHAM组,OVX组,OVX+戊酸雌二醇(E2)组和OVX+替勃龙(tibolone,TIB)组。灌胃13周后处死动物,第四腰椎行骨组织形态计量指标测定,第二腰椎采用RT-PCR方法,对OPGmRNA表达水平进行检测。结果:OVX组大鼠较SHAM组TBV%显著下降;OSV%明显升高(P<0·05);E2和TIB均可使OVX大鼠的TBV%明显升高,OSV%明显下降;OPGmRNA表达水平在OVX大鼠组织中下调,与SHAM组相比有显著性差异(P<0.05),E2和TIB均可上调OVX大鼠骨组织OPGmRNA表达水平(P<0.05)。结论:E2和TIB均通过抑制骨转换预防和治疗PMOP;PMOP的发生与OPG有关,TIB和E2一样,其抗骨吸收效应很可能是通过OPG介导的。     

口服替勃龙或替勃龙加妊马雌酮对绝经后乳腺增生的影响

目的:观察绝经后口服替勃龙以及替勃龙加妊马雌酮两种治疗方案对乳腺增生的影响,评估替勃龙及其配伍方案作为激素补充治疗方案的安全性。方法:5 0例绝经后伴有乳腺增生病例,随机分为两组,分别接受替勃龙1.2 5mg每日1次或替勃龙1.2 5mg每日1次加妊马雌酮0 .3mg隔日1次,共服用6个月。并在用药前、用药6个月后行乳腺B超检查,根据治疗前后乳腺B超报告的乳腺导管、纹理及结节的变化情况分别比较两组用药前后的对乳腺增生的影响。结果:替勃龙组治疗后,双侧乳腺导管明显缩小,治疗前后差异有非常显著性(P <0 .0 1)。替勃龙加妊马雌酮组治疗后变化小,治疗前后差异无显著性(P >0 .0 5 )。用药前后替勃龙组左侧乳腺导管治疗变化百分比较替勃龙加妊马雌酮组改变明显(P <0 .0 5 ) ,单纯替勃龙组用药前后乳腺纹理增粗、乳腺结节对比变化有显著性(P <0 .0 5 ) ,而替勃龙加妊马雌酮组变化没有显著性(P >0 .0 5 )。结论:对于有绝经症状并患有乳腺增生的妇女应选择对乳腺影响小又能缓解症状的药物,替勃龙应该是一种较好的选择。     

孕激素对去势雌性大鼠血脂及血管病理形态学的影响

目的:研究孕激素对去势雌性大鼠血脂及血管病理形态学的影响。方法:随机将50只6月龄SD雌性大鼠分为5组:假手术组(A)、卵巢切除组(B)、卵巢切除加补佳乐(Progynova)2mg加甲羟孕酮(MPA)2mg组(C)、卵巢切除加MPA10mg组(D)、卵巢切除加MPA20mg组(E)。手术7天后开始喂药,用药后3个月处死。测定各组大鼠血脂及血管病理形态学的变化。结果:总胆固醇(TC):卵巢切除后各组TC降低,与A组的差异有统计学意义(P<0.05),B组、C组、D组、E组的差异无统计学意义(P>0.05);甘油三脂(TG):A组与C组无差异,B组、D组、E组TG降低,与A组、C组的差异有统计学意义(P<0.05);高密度脂蛋白胆固醇(HDL-C):卵巢切除后各组HDL-C降低与A组的差异有统计学意义(P<0.05),B组、C组、D组、E组的差异无统计学意义(P>0.05);低密度脂蛋白胆固醇(LDL-C):D组与E组无差异,D组、E组LDL-C降低,与A组、B组、C组的差异有统计学意义(P<0.05),B组、C组、D组LDL-C降低,与A组的差异有统计学意义(P<0.05)。脂蛋白(a)[Lp(a)]:A组、B组、C组、D组、E组之间差异有统计学意义(P<0.05);载脂蛋白-A(apo-A)及载脂蛋白-B(apo-B)各组之间差异无统计学意义(P>0.05)。结论:大鼠去势后MPA及雌激素替代治疗(ERT)对血脂影响与激素类型、激素剂量有关,但对血管病理形态学无影响。     

不同剂量替勃龙联合牡蛎碳酸钙片对绝经后妇女骨质疏松症影响的临床研究

目的：对绝经后妇女应用小剂量替勃龙联合牡蛎碳酸钙片为期3年的前瞻性研究。方法：服药剂量每日1.25mg（1/2量组）加牡蛎碳酸钙片3片50例和每日0.625mg（1/4量组）加牡蛎碳酸钙片3片50例。用于药前及药后每6个月随诊,分别观察骨密度、尿Ca/Cr比值、子宫大小、子宫内膜厚度,乳腺腺体密度变化、血生化检查等。结果：两组经SPA测量骨密度均有上升。其中1/2量组治疗后上升6.8%,与治疗前相比有显著差异（P〈0.001）,1/4量组治疗后上升2.3%,与治疗前相比无显著差异（P〉0.05）;两组尿Ca/Cr比值相应的下降率分别为10.2%与7.5%;两组子宫内膜厚度虽有所增加,但平均厚度均未超过0.5cm;两组乳腺腺体密度无明显变化;两组血生化值无明显差异。结论：绝经后妇女应用1/2量替勃龙联合牡蛎碳酸钙片3片可提高骨密度,1/4量替勃龙联合牡蛎碳酸钙片3片可维持骨量;对子宫内膜无明显刺激作用;对乳腺腺体密度无明显改变。结果显示替勃龙联合牡蛎碳酸钙片能有效地用于防治绝经后妇女骨质疏松症,副作用小,值得推广。     

替勃龙片联合甲硝唑栓治疗萎缩性阴道炎的疗效研究

目的 探讨替勃龙片联合甲硝唑栓治疗萎缩性阴道炎的临床疗效。方法 选取104例萎缩性阴道炎患者,根据随机数字表法分为单一组与联合组,每组52例。单一组采用替勃龙片治疗,联合组采用替勃龙片联合甲硝唑栓治疗,比较两组临床疗效。结果 单一组患者阴道灼热感治疗时间（17.52±0.79）d、阴道瘙痒治疗时间（12.72±0.05）d、白带异常治疗时间（18.30±2.59）d,联合组分别为（9.74±1.20）、（8.13±0.39）、（10.34±1.42）d,联合组各症状治疗时间均明显短于对照组,差异具有统计学意义（P<0.05）。治疗前,两组阴道pH值比较,差异无统计学意义（P>0.05）;治疗后,两组阴道pH值低于治疗前,且联合组低于单一组,差异具有统计学意义（P<0.05）。联合组治疗总有效率为96.2%,明显高于单一组的84.6%,差异有统计学意义（P<0.05）。联合组不良反应发生率低于对照组,差异有统计学意义（P<0.05）。结论 替勃龙片联合甲硝唑栓治疗萎缩性阴道炎疗效显著,不仅可缩短患者治疗时间,调整患者阴道pH值,还可降低不良反应发生率,值得临...     

替勃龙对上皮性卵巢癌患者术后生存质量的影响

目的探讨替勃龙对上皮性卵巢癌患者术后生存质量的影响。方法选取自2009年1月至2010年8月在盛京医院手术且病理诊断为上皮性卵巢癌的患者,在术后规范化疗过程中,进行Kupperman量表调查,将评分大于15分的患者根据是否愿意使用替勃龙药物治疗分为两组,实验组术后给予替勃龙2.5mg,每日1次口服,持续6个月。不愿意用药者为对照组。将30例完成6个月服药的卵巢癌患者按照临床期别及年龄与未服药的患者非随机配对进行分析。结果①Kupperman量表：患者服药6个月实验组评分为（4.97±1.88）分,明显低于对照组评分（20.53±5.16）分,差异有统计学意义（P〈0.001）;②EORTC-C30量表：功能子量表：实验组在身体功能、情绪功能、社会功能、角色功能等方面较对照评分高,与对照组比较差异有统计学意义（P〈0.05）;症状子量表：实验组在失眠、恶心、呕吐、疲劳、食欲等症状方面评分低,与对照组比较差异有统计学意义（P〈0.05）;总体健康情况评分：实验组显著高于对照组;③在化疗副反应方面：周围神经症状,实验组与对照组相比,实验组周围神经症状较轻,差异有统计学意义（P〈0.05）;白细胞计数：实验组较之对照组差异无统计学意义（P〉0.05）。结论替勃龙可明显改善上皮性卵巢癌术后患者雌激素缺乏症状,减轻化疗副反应,提高患者的生存质量。     

坤泰胶囊联合地屈孕酮和替勃龙治疗更年期综合征的临床疗效及对激素水平的影响

目的探讨分析坤泰胶囊联合地屈孕酮和替勃龙治疗更年期综合征的临床疗效及对激素水平的影响。方法从2018年1月~2019年3月于我院收治的更年期综合征患者病例中,选取100例作为研究对象,随机分为屈孕酮组和替勃龙组,各为50例,对两组患者治疗效果和激素水平变化等进行对比和观察。结果地屈孕酮组的临床总有效率与替勃龙组对比差异并不显著,无统计学意义(P>0.05);在治疗后,两组患者各项激素水平均出现明显的变化,且替勃龙组明显优于对照组,对比差异显著(P<0.05)。结论在治疗更年期综合征中,坤泰胶囊联合地屈孕酮和替勃龙,具有显著的治疗效果,替勃龙组可以将患者体内雌激素水平提升上来,确保患者生活质量的稳步提升,其临床推广和应用价值显著。     

RU486对OHSS模型大鼠血管内皮生长因子产生的作用

目的:探讨RU486对卵巢过度刺激综合征(OHSS)模型大鼠血管内皮生长因子(VEGF)产生的作用。方法:30只22日龄雌性大鼠,从22日龄起每天皮下注射10IUPMSG连续4d,26日龄时皮下注射100IUhCG,建立OHSS模型。在27日龄将上述大鼠随机分成5组,每组6只。其中4组(A-D组)为实验组,分别皮下注射不同剂量(1mg/kg、5mg/kg、10mg/kg、20mg/kg)的RU486;另一组为对照组不给药。RU486注射48h后,采用酶联免疫吸附试验方法测定血清和腹腔冲洗液中VEGF水平;采用免疫组织化学法和逆转录聚合酶链反应技术检测卵巢组织VEGF蛋白质和mRNA的表达。结果:B组和C组的血清VEGF水平分别为55.00±14.13pg/ml和49.67±17.44pg/ml,均显著低于对照组(76.17±18.19pg/ml)(P<0.05)。同样,B组和C组的腹腔VEGF水平分别为10.43±6.80pg/ml、10.30±5.82pg/ml,也均显著低于对照组(17.12±1.71pg/ml)(P<0.05)。B组和C组的卵巢组织VEGF蛋白质和mRNA的表达显著低于对照组(P<0.05)。结论:适当剂量的RU486能够降低OHSS模型大鼠VEGF的产生。     

去卵巢大鼠心脏结构和心肌细胞的改变

目的：研究去卵巢大鼠心脏结构、功能以及心肌纤维化情况。方法：将20只Sprague-Dawley （SD）雌性大鼠随机分为假手术组（Sham组）和去卵巢组（OVX组）,行超声心动图（UCG）检查,取心脏组织石蜡包埋,行HE及Masson染色。结果：与Sham组相比,OVX组左心室室间隔厚度明显增厚（P＜0.05）,心肌细胞面积与心肌细胞核面积显著增大（P＜0.01）,心脏胶原容积分数以及心脏血管周围胶原面积明显增多（P＜0.05）。结论：去卵巢大鼠左心室室壁显著增厚,心肌细胞和间质胶原均出现重构改变。     

抗子宫内膜抗体对大鼠不孕及自然流产的影响

目的:了解抗子宫内膜抗体(EMAb)对大鼠妊娠的影响。方法:按高、低2种剂量将纯化入子宫内膜抗原(EMAg)1ml注入大鼠腹腔;以同期腹腔注射1ml生理盐水为对照组,利用间接ELISA检测血液中EMAb阳性水平,电化学发光法检测血液中的CA-125水平,并观察其对妊娠及其结局的影响。结果:EMAb阳性率、不孕率、胎盘重量、胎盘直径实验组高于对照组(P＜0．05或P＜0．01),孕鼠所产仔鼠数、仔鼠体重实验组低于对照组(P＜0．05或P＜0．01),CA-125水平、仔鼠身长各组间无差异(P＞0．05),各组流产率、畸形率均为0。组织病理学显示,实验组EMAb阳性的未孕子宫内膜腺细胞排列欠规则,其内呈空泡改变,明显不同于对照组未孕子宫。结论:①腹腔注射纯化入EMAg能诱导大鼠体内产生EMAb。②EMAb能够导致大鼠不孕,并使其产仔数及仔鼠体重下降。③EMAb能够导致大鼠胎盘的重量和直径增加,且高剂量组(180μg/kg)明显高于低剂量组(90μg/kg)。     

Effects of Serum from Preeclamptic Women on Prostacyclin Production by Human Endothelial Cells

There is growing evidence that proteinuric hypertension of pregnancy (preeclampsia) is associated with endothelial dysfunction. The aim of this study was to evaluate the effects of serum from preeclamptic patients on basal and agonist-stimulated prostacyclin production by human umbilical vein endothelial cells (HUVEC) in culture and to compare these to the effects of serum from normal pregnant and nonpregnant women. During a 24 h incubation of HUVEC with 20% preeclampsia serum, baseline prostacyclin output was significantly (P < 0.01) increased over the control groups. However, this response was attenuated by extending the exposure to 72 h. Histamine, thrombin and the calcium ionophore, A23187, all acutely increased prostacyclin production, but the increase relative to baseline levels was greatest in HUVEC preincubated for 24 h in normal serum and was smallest when cells were preincubated in preeclampsia serum. We conclude that 1) preeclampsia serum transiently promotes prostacyclin production in HUVEC derived from normal pregnancies, and 2) the relative increase in response to agonists is reduced by preeclampsia serum, compared to normal pregnancy sera.     

Effects of tibolone on the breast

Objective: to evaluate the effect of hormone replacement therapy and tibolone on the breast. Study design: prospective, controlled, randomized study. Setting: Outpatient Menopause Clinic of the Second University of Naples. Participants: forty four women in spontaneous menopause without any risk factor for breast cancer were randomly allocated to three groups: 15 patients (group A) were treated with transdermal oestrogens 50 μg, 2 patches/week for 3 weeks per month, plus acetate nomegestrolo per os 5 mg/die for 12 days per cycle, 17 patients (group B) were treated with tibolone 2.5 mg/die. Twelve patients not given any medication represented the control group (group C). Methods: at the time of recruitment and after at least 12 months of therapy the patients were subjected to a questionnaire aimed at quantifying the slight, moderate or severe presence of the tension/mastodynia symptoms and to a mammographic test to assess the parenchymal pattern according to a quantitative method: type 1 (less than 25% of mammary gland covered by dense tissue), type 2 (from 25% to 75% of total glandular area covered by dense tissue), type 3 (more than 75% of mammary parenchyma covered by dense tissue). Statistical analysis was carried out by means of Fisher's exact test. Results: after at least 12 months of treatment in Group A 5 out of 15 patients (33%) showed a trend of increase in mammographic density not statistically significant (P=0.22) when compared with group B in which one patient showed a swift from type 1 to type 2 and another from type 2 to type 3. The analysis of tension/mastodynia symptoms revealed a significantly difference between the two groups (P=0.02): in group A mastodynia appeared in three previously asymptomatic women and increased in five women, with a total increase in the symptomatology in 8 out of 15 patients (53.3%), in group B only in one case (5%) mastodynia turned from slight to moderate. Conclusion: in postmenopausal women oestroprogestogenic replacement therapy may be associated with an increase in mammographic density and with the onset or increase in mastodynia. On the contrary tibolone does not seem to affect normostructured mammas and may be considered a first-rate replacement therapy in case of mammas showing particular density or benign mastopathies.     

Effects of tibolone and its metabolites on prolactin and insulin-like growth factor binding protein-1 expression in human endometrial stromal cells

Abstract

The effects of the postmenopausal replacement steroid tibolone and its 3α-, 3β-OH and Δ-4 tibolone metabolites were evaluated on progesterone receptor-mediated classic decidualization markers insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin expression in human endometrial stromal cells (HESCs). Supernatants of conditioned medium or erxtracted RNA from experimental cell incubations of confluent HESCs were subjected to ELISAs, Western blot analysis and RT/PCR, and results were statisically assesed. Over 21 days, specific ELISAs observed linear increases in secreted IGFBP-1 and prolactin levels elicited by tibolone and its metabolites. Cultured HESCs were refractory to E2 and dexamethasone, whereas tibolone and each metabolite exceeded medroxyprogesterone acetate in significantly elevating IGFBP-1 and prolactin output. Anti-progestins eliminated IGFBP-1 and prolactin induction by tibolone and its metabolites. Immunoblotting and RT/PCR confirmed ELISA results. These observations of IGFBP-1 and prolactin expression: (a) indicate the relevance of cultured HESCs in evaluating the chronic effects of tibolone administration to women; (b) are consistent with PR-mediated endometrial atrophy and protection against endometrial bleeding despite the persistence of circulating ER-binding, but not PR-binding metabolites following tibolone administration to women.     

雌激素对去势大鼠端粒酶活性的影响

目的:探讨雌激素对去势雌性SD大鼠端粒酶活性的影响,从而研究其抗衰老作用机制。方法:将33只3个月龄雌性大鼠随机分为3组,去势实验组(11只)开始用戊酸雌二醇(E2)+0.9%氯化钠溶液按0.21 mg/kg灌胃,去势对照组(11只)、假手术组(11只)给予等量0.9%氯化钠溶液灌胃,1次/d。12周后腹主动脉采血,酶联免疫吸附测定(ELISA)法测定血清E2、卵泡刺激素(FSH),处死大鼠后快速摘取心脏、肝脏、脑组织,通过逆转录聚合酶链反应(RTPCR)和ELISA法分别检测各组织端粒酶活性及端粒酶逆转录酶(TERT)m RNA水平。结果:去势实验组和假手术组血清E2水平高于去势对照组,血清FSH水平低于去势对照组(均P0.05);去势实验组端粒酶活性的ΔA值高于去势对照组和假手术组(均P0.05),去势对照组和假手术组端粒酶的活性均为阴性,ΔA值较低,差异无统计学意义(P0.05);去势实验组大鼠心脏、肝脏和脑组织TERT m RNAΔCt值低于去势对照组及假手术组(均P0.05),而去势对照组和假手术组TERT m RNAΔCt值差异无统计学意义(均P0.05)。结论:雌激素可以显著提高去势雌性大鼠端粒酶活性及TERT m RNA水平,进而发挥其抗衰老作用。     

Effect of tibolone on markers of cardiovascular disease risk in postmenopausal women undergoing hemodialysis: a pilot study

OBJECTIVE: To assess the effect of tibolone on markers of vascular risk in postmenopausal women who were receiving hemodialysis. DESIGN: One-year open-label study. SETTING: "Zvezdara" University Medical Center, Belgrade, Serbia. PATIENT(S): Twenty-eight postmenopausal women undergoing chronic hemodialysis. INTERVENTION(S): Fifteen women received tibolone 2.5 mg three times per week; 13 other women served as controls. MAIN OUTCOME MEASURE(S): Mean arterial pressure and weight were measured at baseline and at 6 and 12 months, and blood was collected for insulin, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, lipoprotein(a), high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and markers of renal function. RESULT(S): Mean arterial pressure fell in the tibolone but not in the control group at 6 and 12 months versus baseline (mean [SD]: 93 [15] vs. 105 [11] mmHg and 94 [10] vs. 105 [11] mmHg, respectively). Weight, insulin, lipids, lipoprotein(a), hs-CRP, ET-1, VEGF, and renal function remained unchanged within each group, but high-density lipoprotein concentrations fell in the tibolone group after 12 months (1.2 [0.3] vs. 1.6 [0.6] mmol/L). CONCLUSION(S): The effects of tibolone on markers of vascular risk in postmenopausal women who are receiving hemodialysis and healthy women appear to differ. This should be taken into account when tailoring menopausal therapies to the specific requirements of each individual.