雌激素对去卵巢大鼠骨丢失的骨形态计量学及组织 …

目的 了解大鼠卵巢性激素缺乏致骨丢失的组织学改变以及四种不同雌激素制剂对其的影响。方法 将５０只ＳＤ大鼠随机分为６组,去势且（９只）在去势手术后３周处死大鼠;对照组（９只）开腹后关腹;去势＋利维爱组、去势＋盖福润组、去势＋倍美力组、去势＋维尼安组（各８只）在去势手术后３周予相应的药物治疗,术后６周（药物治疗后３周）处死各组大鼠,进行骨形态计量学、骨密度（ＢＭＤ）测定,并行病理及电镜下观察。结果 （     

雌激素对去卵巢大鼠骨丢失的骨形态计量学及组织学的影响

OBJECTIVES: To demonstrate the histomorphometric and histological changes of bone 3 weeks after bilateral ovariectomy in rats and to investigate the impacts of 4 different hormone replacement therapies on the bone histomorphometric, histological appearances. METHODS: Bilateral ovariectomies were done on 41 female rats and sham operations on other 9 (sham group) respectively. After 3 weeks, 4 different treatments: i.e. Livial, Gevrine, Premarin, Weinian were initiated separately on each 8 ovariectomized rats for another 3 weeks. The remaining 9 were served as controls (OVX group). All rats were sacrificed either 3 weeks after ovariectomy/sham operation or at the end of hormone therapies. Their femoral bone mineral density (BMD) were measured by dual energy X-ray absorptiometry (DEXA). Specimens of proximal femur were embedded undecacifide for histomorphometric analysis and of distal femoral metaphysics were procured for scanning electron microscope (SEM) and pathologic examinations. RESULTS: (1) Three weeks after OVX, the femoral BMD, mean cortical thickness decreased significantly while the number of osteoclast increased significantly as compared with sham group. The trabecular became thinner and irregular which changed the bone microstructure in three dimension. (2) After treatment of 4 different preparations, the above parameters restored to various extents to the sham operation levels. Among them, there was greater increase of femoral BMD on the Livial and Gevrine group as compared with Premarin and Weinian group (P < 0.05). CONCLUSIONS: Bilateral ovariectomy induced increased osteoclast activity and bone turnover, therefore caused accelerated bone loss. Treatment with combined sex hormones preparation could inhibit bone absorption and stimulate bone formation, especially those containing androgenic activity could increase the BMD.     

结合雌激素联合方案连续应用防治绝经早期妇女骨量丢失的观察

目的　探讨两种剂量结合雌激素 (CEE)对绝经早期妇女骨丢失的影响及副作用。方法将 2 36例绝经妇女分为 3组 ,A组每日口服CEE 0 62 5mg+醋甲羟孕酮 (MPA) 2mg +钙剂 (Ca D) 1片(含元素钙 60 0mg) ;B组每日口服CEE 0 3mg +MPA 2mg +Ca D 1片 ;C组每日仅服Ca D 1片 ,连续用药 2年。于治疗前、治疗 1 2及 2 4个月测量第 2～ 4腰椎 (L2～ 4 )的骨密度 (BMD) ,记录每月阴道出血情况。结果　A组治疗前、治疗 1 2及 2 4个月 ,L2～ 4 BMD分别为 (1 0 62± 1 4 1 )、(1 0 86± 1 4 5)及 (1 1 0 1±1 34)mg/cm2 ,治疗前后比较 ,差异均有极显著性 (P <0 0 0 1 ) ;B组分别为 (1 0 81± 1 35)、(1 1 1 1± 1 68)及(1 0 90± 1 50 )mg/cm2 ,治疗 1 2个月时与治疗前比较 ,差异有显著性 (P <0 0 5) ,治疗 2 4个月时与治疗前比较 ,差异无显著性 (P >0 0 5) ;C组分别为 (1 0 70± 1 1 9)、(1 0 65± 1 34)及 (1 0 53± 1 30 )mg/cm2 ,治疗前后比较 ,差异均无显著性 (P >0 0 5)。治疗前后BMD的变化 ,A与C组、B与C组之间差异均有显著性 (P <0 0 0 1 ,<0 0 5) ;A与B组治疗 1 2个月时的BMD比较 ,差异无显著性 (P >0 0 5) ,2 4个月时比较 ,差异有极显著性 (P <0 0 1 )。各组子宫内膜均无不典型增生。A、B组出血率 ,治     

对氯烯雌酚醚防治雌性大鼠去势后骨丢失的评价

目的：了解氯烯雌酚醚对去势雌性大鼠骨代谢的影响。方法：鼠龄７０天的Ｗｉｓｔａｒ雌鼠４８只，分别予假性手术与注射用油（ＳＶ组）、去势与注射用油（ＯＶ组）、假性手术与氯烯雌酚醚（ＳＥ组）及去势与氯烯雌酚醚（ＯＥ组）等处理，双侧卵巢去势或假性手术后７天，于每晚腹腔注射氯烯雌酚醚或注射用油４ｍｌ／ｋｇ，共４５天。处死大鼠时，测定子宫湿重，同时收集第１２胸椎和左胫骨制成脱钙骨切片，行骨组织形态计量学测定。结果：４组间子宫重量差异均有显著性。骨组织形态计量学显示，（１）ＯＶ与ＳＶ、ＳＥ及ＯＥ组间差异有显著性；（２）ＯＥ、ＳＥ和ＳＶ组间差异无显著性。结论：氯烯雌酚醚能抑制Ｗｉｓｔａｒ雌鼠去势后的骨丢失，减缓去势后的子宫萎缩，对骨骼有雌激素样的保护作用。     

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。     

三苯氧胺治疗绝经前后子宫内膜癌的效果观察

目的：比较绝经前、后子宫内膜癌患者经三苯氧胺治疗后血清性激素，癌组织雌、孕激素受体及子宫内膜癌组织学的改变，探讨三苯氧胺治疗的作用机理及效果。方法：４０例确诊为子宫内膜癌的患者，分为绝经前组（２８例）及绝经后组（１２例），给予三苯氧胺每次２０ｍｇ，每天３次，口服１０天，观察血清性激素等指标的改变。结果：两组患者癌组织的病理组织学有一定程度改变，表现为癌细胞向分化好的方向发展，以核浆比例下降、核分裂相减少、核形态向圆形转变为特征。用药后，绝经前患者促卵泡刺激素升高，癌组织雌激素受体（ＥＲ）含量或升高或下降，孕激素受体（ＰＲ）含量增加。绝经后患者卵泡刺激素下降，癌组织ＥＲ、ＰＲ含量以增加为主。结论：三苯氧胺对子宫内膜癌有一定治疗效果。对绝经前患者，三苯氧胺表现为抗雌激素作用；对绝经后患者，则表现为弱雌激素样作用。     

经皮用雌二醇凝胶预防绝经早期骨丢失的三年探索性观察

目的 探索经皮用雌二醇（E2）凝胶在中国妇女中预防绝经早期骨丢失的用法。方法 将60例身体健康、绝经1－5年的妇女,开放随机分为4组,每组15例,采用周期联合方法分别予含0．75或1．5mgE2的经皮17β-E2凝胶（E2凝胶）与100mg微粉化天然黄体酮（MP）或2mg醋甲羟孕酮（MPA）口服,每日睡前应用,每月连用25d,停药5d。用单光子吸收法测前臂皮质骨骨密度;定量CT法测腰椎松质骨骨密度;双能X线吸收法测腰椎与髋部骨密度。在治疗0、6、12、18、24与36个月时分别测量骨密度、骨代谢生化指标,行绝经症状评分。结果 59例（98％）完成1年;56例（93％）完成2年,51例（85％）完成3年。治疗6个月时,4个组症状缓解率平均约80％;2年时腰椎松质骨骨密度升高平均为4．3％－7．5％;3年时第2－4腰椎骨密度升高4．2％－6．2％;股骨颈骨密度升高1．6％－3．8％。与治疗前相比,差异均有显著性（P＜0．05）;4组间比较,骨密度的改善差异无显著性（P＞0．05）。阴道出血率1．5mgE2凝胶＋2mgMPA治疗者、0．75mgE2凝胶＋2mgMPA治疗者较高,其他两组较低。结论 每日0．75mg与1．5mgE2凝胶可有效缓解绝经相关症状,预防绝经早期骨丢失。雌孕激素补充治疗3年,可连续增加腰椎骨密度,增加并维持股骨上端骨密度。     

三苯氧胺的雌激素样作用

三苯氧胺的雌激素样作用２５００１２山东医科大学附属医院张师前６１００４１四川省肿瘤医院张国楠综述李家福审校三苯氧胺（ｔａｍｏｘｉｆｅｎ；ＴＡＭ）作为一种非甾体类抗雌激素药自１９７１年开始应用于治疗乳腺癌以来已有３０余年的历史，现已成为乳腺癌患者特别是...     

三苯氧胺对子宫内膜的影响

目的：观察乳腺癌患者服用三苯氧胺（TAM）后对子宫内膜的影响。方法：26例乳腺癌患者服用TAM（TAM组）后出现阴道异常出血或B超检查发现子宫内膜增厚而行宫腔镜检查及子宫内膜病理检查。另外以同时期无TAM服药史的非乳腺癌患者因绝经后阴道出血而行宫腔镜检查的78例作为对照组。结果：TAM组发生子宫内膜息肉和宫颈息肉共13例（50.0%）,而对照组为14例（17.9%),两组比较,差异有显著性（P＜0.05)。TAM组发生子宫内膜增生9例（34.6%),明显高于对照组的12例（15.4%,P＜0.05)。结论：乳腺癌患者长期服用TAM后子宫内膜病变增多,故对这些患者应进行B超监测子宫腔镜检查。     

三苯氧胺对人乳腺癌的雌激素受体的上调作用

东莞氧胺(TMX)为一非固醇类雌激素拮抗剂,广泛用于晚期和复发乳腺癌。TMX使约60％雌激素受体(ER)阳性和10％ER阴性的乳腺癌肿缩小。一些临床试验表明,对ER阳性的绝经后乳腺癌患者TMX可作为一有效辅助治疗。目前尚未阐明在体内TMX治疗对人乳腺癌ER和孕激素受体(PR)水平的影响。在本研究中,作者试图从同一乳腺癌中获得系列细针穿刺吸引(FNA)标本,用酶联免疫法(EIA)检测TMX对人乳腺癌ER水平的影响及对PR的影响。     

尼尔雌醇对去卵巢大鼠胫骨作用的研究

目的 了解卵巢切除（ＯＶＸ）大鼠胫骨对雌激素治疗的反应。方法 将３３只雌性大鼠随机分成３组,每组１１只：ＯＶＸ组、对照组和治疗组。对ＯＶＸ组与治疗组大鼠行ＯＶＸ手术,建立骨质疏松动物模型,治疗组于ＯＶＸ术后１个月予尼尔柴醇喂养,药物喂养３个月后处死,用骨形态计量学方法检测ＯＶＸ大鼠左后肢胫骨干骺端对纪尔雌醇治疗的反应。结果 ＯＶＸ组大鼠骨小梁体积小、平均骨小梁宽度、平均骨小梁密度和皮质骨平均厚度（     

四种补肾中药对去卵巢大鼠骨质疏松骨形态的作用

目的 比较骨碎补、锁阳、淫羊藿和狗脊４种补肾中药对去卵巢（ＯＶＸ）大鼠骨质疏松的作用。方法 将５４只３月龄雌性Ｗｉｓｔａｒ大鼠随机分成模型组和中药治疗组。模型组包括非手术组、假手术组和去卵巢组,每组１０只;中药组包括骨碎补组、锁阳组、淫羊藿组和狗脊组,每组６只。去卵巢手术后１周,中药组分别用上述４种中药喂养,８周后放血外死全部小鼠,用骨形态主坦学方法比较４种中药对ＯＶＸ大鼠骨质疏松的防治作用。结果     

Glycosaminoglycan profiles in the uterus of adult ovariectomized rats treated with estrogen and progestagen

Objectives

To evaluate the effects of conjugated equine estrogens (CE) alone or in combination with medroxyprogesterone acetate (MPA) on glycosaminoglycans (GAGs) in the cervix and horns of the rat uterus.

Study design

Thirty days after ovariectomy, adult rats were randomly divided into four groups: GI, control (treated with drug vehicle); GII, CE (50 μg/kg per day); GIII, MPA (0.2 mg/kg per day), and GIV, CE + MPA (doses as in GII and GIII). Drugs and vehicle were given by gavage during 28 days. Afterwards the animals were anesthetized, the cervix and uterine horns were dissected out and the middle portion fixed in 10% formaldehyde solution; other portions were fixed in acetone for histological examination and glycosaminoglycan quantification, respectively. Agarose gel electrophoresis was used for sulfated GAG analyses, and hyaluronic acid was assayed with an ELISA-like method. Statistical analysis was done by the Student's t test and the Tukey–Kramer test (P < 0.05).

Results

The cervix and uterine horn structures presented signs of atrophy in the control group (GI). The other groups, mainly groups III and IV, had histological aspects of proliferation. In all groups the concentration of sulfated GAGs (especially dermatan sulfate) was higher than that of non-sulfated GAGs, both in cervix and in uterine horns. Estrogens increased sulfated GAG concentration at the cervix and the horn, whereas in uterine horns the amounts of sulfated GAGs were decreased after estrogens plus MPA treatment. The concentration of hyaluronic acid in uterine horns was higher than in cervices.

Conclusions

The profiling and amounts of glycosaminoglycans in the two portions of the rat uterus are uneven. Dermatan sulfate occurs in higher concentrations in both cervix and uterine horns. Sulfated GAGs in rat cervix were increased by estrogens plus MPA, but were decreased by MPA alone in uterine horns.     

四环素-雌酮和雌酮作用去势大鼠的骨形态计量学对照研究

目的比较四环素－雌酮和雌酮对卵巢切除（ＯＶＸ）大鼠股骨远端骨干骨形态参数的影响。方法２０只雌性大鼠随机分成４组,每组５只：四环素－雌酮治疗组、雌酮治疗组、ＯＶＸ组和假手术组,建立ＯＶＸ大鼠骨质疏松动物模型,药物喂养１３周后处死,用骨形态计量学方法研究四环素－雌酮和雌酮对骨形态和动力学参数的影响。结果与假手术组相比,四环素－雌酮组和雌酮组骨小梁的连接性均明显地高于假手术组（Ｐ＜０．０５）。与ＯＶＸ组相比,四环素－雌酮和雌酮组四环素标记表面和类骨质表面均明显增加,四环素－雌酮组的结果又明显高于雌酮组,更明显高于其它两组（Ｐ＜０．０５）。结论四环素－雌酮和雌酮可以明显地加强骨小梁的连接性,四环素－雌酮提高骨激活频率的作用优于雌酮。     

Effect of long-term hormone replacement therapy on the bone in ovariectomized women with cancer

Objective: To evaluate longitudinally the effectiveness of long-term hormone replacement therapy (HRT) in preserving the bone mineral density (BMD) over a 5-year period in ovariectomized patients treated for gynecologic malignancies. Methods: A total of 70 pre-menopausal women ovariectomized for gynecologic malignancies at our hospital were divided non-randomly into two groups: HRT (+) group (n=59) and HRT (−) group (n=11). HRT was administered in a sequential regimen of 0.625–1.25 mg conjugated estrogen for 24 days and 5–10 mg medroxyprogesterone acetate for 10 days. Results: The BMD of the lumbar vertebrae decreased significantly in the HRT (−) group (pre-operative BMD was 91.8%, 91.0% and 91.3% at 1, 2 and 3 years post-ovariectomy), but no decrease in the BMD was observed in the HRT (+) group (pre-operative BMD was 98.4%, 99.0%, 99.4%, 98.8% and 98.7% at 1, 2, 3, 4 and 5 years post-ovariectomy); the difference in BMD between the two groups was statistically significant (P<0.01). Serum alkaline phosphatase levels were significantly lower in the HRT (+) group than in the HRT (−) group (P<0.01). There were four recurrences of cancer in the HRT (+) group. Conclusion: HRT appeared to have beneficial effects on bone metabolism by maintaining BMD for 5 years in ovariectomized patients for gynecologic malignancies.     

绝经后不同时期骨丢失的初步探讨

目的探讨妇女绝经后早期与晚期的骨丢失特点及骨转换规律,评价生化指标对预测骨丢失的意义。方法对３２例绝经１～３年（绝经早期组）妇女及３３例绝经１５～３０年（绝经晚期组）妇女,在试验初始（０个月）、６、１２个月分别测定骨密度、血总碱性磷酸酶、骨钙素、骨碱性磷酸酶、尿钙／尿肌酐、尿吡啶啉。结果绝经早期组妇女６、１２个月脊柱平均骨丢失率为１．３％、２．６％;股骨部位骨丢失不明显;腰椎骨丢失率＞３％（快速丢失）的１５例,＜３％（慢速丢失）的１７例。绝经晚期组６、１２个月股骨颈,Ｗａｒｄ＇ｓ三角骨丢失率分别为１．３％、１．９％,５．３％、４．６％,腰椎骨丢失不明显。两组尿吡啶啉随时间呈上升趋势,血骨钙素、骨碱性磷酸酶水平随时间变化趋势相似。生化指标与腰椎骨丢失率之间无相关性。结论绝经早期妇女骨丢失以腰椎部位敏感,快速与慢速骨丢失者约各占一半。绝经晚期妇女骨丢失以股骨颈、Ｗａｒｄ＇ｓ三角区显著,以慢速骨丢失者为主。两组妇女骨转换均增强     

The effects of transdermal estrogen therapy on bone mass and turnover in early postmenopausal smokers: a prospective, controlled study

OBJECTIVE: The purpose of this study was to investigate whether smoking reduces the effects of transdermal estrogen replacement therapy on bone. STUDY DESIGN: One hundred forty-eight women (0.5-5 years after menopause, aged 46-58 years) completed the study. Smokers were assigned randomly to receive either 1.0 mg (n=32 women) or 1.5 mg (n=31 women) of transdermal estradiol in gel daily, and nonsmokers (n=46 women) were assigned to receive 1.0 mg of transdermal estradiol for 2 years. The control group consisted of 17 smokers and 22 nonsmokers. Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover was assessed by measurements of urinary aminoterminal telopeptide of type I collagen and serum aminoterminal propeptide of type I procollagen. RESULTS: Lumbar spine bone mineral density increased similarly in smoking (+3.6%) and nonsmoking (+2.6%) estrogen users (P<.0001 to a decrease of 2.5% in the control group). Femoral neck bone mineral density increased 2.2% to 2.4% in smoking and nonsmoking estrogen users but decreased 0.2% in control subjects (P<.05). Urinary aminoterminal telopeptide of type I collagen decreased similarly in all estrogen-using groups (P<.05 to control group), but serum aminoterminal propeptide of type I procollagen decreased more in smoking than in nonsmoking estrogen users (P=.006). Serum 25-hydroxyvitamin D was 20% lower (P=.004) in smokers than in nonsmokers. CONCLUSION: Transdermal estrogen treatment protects smoking women as effectively as nonsmokers from osteoporosis. Smoking worsens the vitamin D state of postmenopausal women.