雌激素替代抑制萘诱导去卵巢大鼠的晶状体氧化损伤

背景：抗氧化作用可能是雌激素对晶状体保护作用的机制之一,但此机制的具体途径目前仍不明确,同时临床上常用的几种雌激素替代治疗方法对晶状体氧化损伤的影响至今少见报道。目的：观察雌二醇及其联合孕酮对萘诱导去卵巢雌性大鼠晶状体氧化损伤模型中晶状体混浊情况、晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平的影响。方法：将SD大鼠随机分为假手术组、模型组、雌二醇组、雌二醇＋孕酮组,后3组均行双侧卵巢切除。术后2周,4组均用萘混悬液灌胃,定期行裂隙灯显微镜检查观察各组大鼠晶状体变化;灌胃6周后检测晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平,测定血清雌二醇和孕酮水平。结果与结论：与模型组相比,雌二醇组、雌二醇＋孕酮组及假手术组晶状体混浊程度轻,出现时间晚,而晶状体超氧化物歧化酶、谷胱甘肽、维生素C,可溶性蛋白含量,血清雌二醇与孕酮水平增高（P〈0.05或P〈0.01）,丙二醛水平降低（P〈0.05）。结果证实,雌二醇及其联合孕酮两种替代治疗方法对萘诱导去卵巢雌性大鼠晶状体的氧化损伤均有抑制作用,其机制与晶状体氧化防御系统的活性、抑制脂质过氧化产物的形成并维持可溶性蛋白的水平有关,抑制晶状体的氧化损伤是雌激素替代治疗发挥晶状体保护作用的机制之一。     

雌激素对雌鼠下尿路雌激素受体表达的影响

目的 研究雌激素对去势雌性大鼠膀胱和尿道组织中雌激素受体（ER）α和β亚型表达的影响。 方法 30只成年雌性大鼠分别假手术处理、卵巢切除、卵巢切除术后苯甲酸雌二醇替代治疗,应用实时定量逆转录聚合酶链反应（RT-PCR）和Western blot方法分析大鼠膀胱底部、膀胱颈部及尿道组织中ERα和ERβmRNA及蛋白表达。 结果 Sham组中,ERαmRNA及蛋白在尿道组织中的表达高于膀胱底部和膀胱颈部,ERβmRNA及蛋白在膀胱底部和膀胱颈部的表达则远高于尿道组织。去势使大鼠膀胱尿道ERαmRNA及蛋白表达增加,补充雌激素治疗使其减少接近假手术组。大鼠膀胱尿道ERβmRNA及蛋白表达在不同雌激素状态下无明显变化。结论 ERβ是主要分布于膀胱,ERα主要分布于尿道组织中。雌激素对雌性大鼠下尿路的调控作用主要通过ERα介导。     

雌激素对大鼠内脏痛觉感受及结肠5-羟色胺合成的影响

目的:研究雌激素对大鼠内脏痛觉感受及结肠5-羟色胺(5-hydroxytryptamine,5-HT)合成的影响。方法:Wistar雌性大鼠采用随机数字表分组,分为假手术组,卵巢切除组及卵巢切除+雌激素组。卵巢切除+雌激素组动物皮下注射苯甲酸雌二醇(30μg·kg~(-1)),连续给药2周。给药结束后次日测定大鼠内脏痛阈值、血清雌激素和孕激素水平;收集结肠组织测定5-HT含量、嗜铬细胞数量及色氨酸羟化酶的表达。结果:雌激素替代给药后显著提高卵巢切除大鼠血清雌激素水平、降低内脏痛阈值、明显提高结肠嗜铬细胞数量、5-HT含量及色氨酸羟化酶的表达。结论:雌激素对结肠5-HT合成具有正性调控作用,该机制可能参与雌激素介导的内脏痛觉感受增强。     

雌激素对去卵巢SD大鼠体重变化影响的研究

目的:探讨去卵巢后十月龄雌性SD大鼠及应用雌二醇替代治疗后对体重的影响.方法:81只十月龄雌性SD大鼠;按体重随机的方法分为去卵巢组(VOX组)、去卵巢加雌二醇注射组(EST组)和假手术组(SHAM组).在进行手术当天及手术后第2天及其后每周测量体重一次,直到14周.结果:大鼠的体重在手术后各组均先下降;然后均有增加,以VOX组为最快,增加到一定程度后,逐步变得平稳;基础体重轻的大鼠体重变化最大.结论:雌激素体内水平的改变,可以直接影响SD大鼠的体重的变化.     

去卵巢大鼠线粒体氧化系统的改变及雌激素对其影响

目的探讨去卵巢大鼠线粒体氧化系统的改变及COX活性以及雌激素对其影响。方法用荧光分光光度计及紫外分光光度计技术检测了去卵巢模型大鼠海马及额叶皮层的SOD、COX活性、MDA含量及线粒体膜流动性的变化。结果去卵巢大鼠海马、额叶皮层SOD活性降低,导致MDA含量明显增加,线粒体膜流动性明显降低,COX活性下降,雌激素替代能增强去卵巢大鼠海马、额叶皮层SOD活性,减少脂质过氧化产物MDA的产生。提高线粒体膜流动性。结论雌激素作为自由基清除剂能增强大鼠脑组织的抗氧化能力,减轻活性氧增多造成的线粒体氧化损伤,减少或延缓神经细胞的衰老、退化,从而对中枢神经系统起保护作用。     

戊酸雌二醇对去势大鼠血液流变学的影响

目的 为探求卵巢切除大鼠在行戊酸雌二醇（一种雌激素）替代治疗后其血液流变学指标的变化。方法 实验动物采用12周正常雌性Wistar大鼠，随机分成假手术组（6只），卵巢切除组（oophorectomized,OOX,10只）和卵巢切除雌激素替代治疗组（estrogen replacement therapy,ERT,10只）。ERT组大鼠在手术4周后，行戊酸雌二醇800mg/Kg/qd替代4周，左心室取血，行血细胞压积，红细胞压积，各切变率下的全血粘度，红细胞变形指数等血液流变学指标的检测，结果 OOX组大鼠的子宫明显出现萎缩，假手术组和ERT组各血液流变学指标间的差异不明显；OOX组低切变率（5s^-1)下的全血粘度值，血浆粘度值，以及红细胞总变形指数和各切变率下的红细胞变形指数均高于假手术组和ERT组；而血细胞压积，高切变率下的全血粘度值和红细胞取向指数三组间的差异不明显。结论 大鼠卵巢切除后行适量的戊酸雌二醇替代治疗，其血液流变学性质可接近于正常鼠水平，而与未行ERT的大鼠存在明显的差异。     

金雀异黄酮对去卵巢大鼠基底前脑一氧化氮合酶神经元的影响

目的:研究去卵巢及金雀异黄酮(genistein,GS)治疗后基底前脑一氧化氮合酶(nitricoxidesynthase,NOS)阳性神经元数目变化,探讨GS改善去卵巢大鼠学习记忆能力的可能机制,为使用GS防治绝经后老年性痴呆提供理论依据。方法:实验于2003-03/2004-01在中山大学人体解剖学教研室脑研究室进行。将36只3月龄雌性SD大鼠分为假手术组、去卵巢对照组、苯甲酸雌二醇组及金雀异黄酮组,每组9只,分别进行干预。术后8周取脑切片,进行NADPH-d组化方法染色,计数分析基底前脑各区NOS阳性神经元数目。结果:各组大鼠基底前脑内侧隔核NOS阳性神经元数目差异无显著性意义(P>0.05);去卵巢对照组斜角带核垂直支及水平支的NOS阳性神经元数目分别为(33.13±9.80)个和(48.55±6.60)个,均高于假手术组、苯甲酸雌二醇组及金雀异黄酮组(P<0.01),金雀异黄酮组斜角带核垂直支及水平支的NOS阳性神经元数目与假手术组、苯甲酸雌二醇组相比差异均无显著性意义(P>0.05)。结论:去卵巢之后大鼠基底前脑一氧化氮增加,产生神经元的毒性作用,使中枢神经系统退行性变导致大鼠学习记能力下降;GS能减少基底前脑一氧化氮水平,有望替代雌激素用于防治疗女性绝经期后中枢神经系统退行性疾病。     

氧化修饰高密度脂蛋白对大鼠颗粒细胞激素分泌的影响及相关机制

目的研究氧化修饰高密度脂蛋白(Ox-HDL)对大鼠颗粒细胞激素分泌的影响及相关机制。方法 30只6周龄SPF级SD雌性大鼠经适应性饲养5 d后,采用孕激素拮抗剂米非司酮进行多囊卵巢综合征(PCOS)大鼠造模。随机选择25只雌鼠,每天对大鼠进行1次皮下注射,每次剂量0.2 mL米非司酮(20 mg/mL),连续14 d。其余5只雌鼠作为对照组。选择造模成功的15只雌鼠,分为模型组,低剂量组及高剂量组,每组5只。对照组及模型组大鼠尾静脉注射0.05 mL生理盐水,连续14 d。低剂量组和高剂量组每天尾静脉注射0.05 m L Ox-HDL溶液(浓度分别为200、400μmol/L),连续14 d。并收集大鼠卵巢颗粒细胞。采用ELISA试验检测大鼠血清雌激素及孕酮水平;采用HE染色检测Ox-HDL对PCOS卵巢病理形态的影响观察;采用Hoechest33258凋亡染色检测大鼠颗粒细胞凋亡水平的影响;采用RT-PCR法检测Ox-HDL对大鼠颗粒细胞Bcl-2、FSHR、StAR及Bax基因表达的作用;采用Western blot法检测Ox-HDL对大鼠颗粒细胞Bcl-2、FSHR、StAR及Bax蛋白表达的作用。结果 PCOS大鼠在Ox-HDL作用后,雌激素及孕酮水平均下降差异有统计学意义(P<0.05),高剂量组的雌激素及孕酮均显著低于其它各组差异有统计学意义(P<0.05)。HE染色发现PCOS大鼠给予高剂量Ox-HDL后,囊肿卵泡进一步增多,颗粒细胞排列较为疏松,大鼠卵巢病理症状有一定加剧。Hoechest33258凋亡染色检测发现高剂量组细胞凋亡水平显著高于其它各组(P<0.05)。RT-PCR实验发现发现Ox-HDL可抑制颗粒细胞Bcl-2、FSHR、StAR基因的mRNA表达水平差异有统计学意义;Ox-HDL可促进颗粒细胞Bax基因的mRNA表达水平差异有统计学意义(P<0.05)。Western blotting实验发现发现Ox-HDL可抑制颗粒细胞Bcl-2、FSHR、StAR蛋白表达水平;Ox-HDL可促进颗粒细胞Bax蛋白表达水平差异有统计学意义(P<0.05)。结论 Ox-HDL可促使PCOS大鼠卵巢病理症状加剧,诱导颗粒细胞发生凋亡,并导致颗粒细胞激素分泌能力紊乱。     

雌激素与葛根素组合治疗去卵巢大鼠骨症的最佳剂量

背景:小剂量的葛根素联合雌二醇对去卵巢大鼠骨质疏松症的治疗效果与单独使用较大剂量的葛根素或较大剂量的雌二醇效果相近。目的:寻找治疗Ⅰ型骨质疏松症最佳的雌二醇和葛根素的剂量搭配。方法:64只健康雌性大白鼠等分为假手术组、去卵巢模型组、葛根素-50组、雌二醇-200组、葛根素+雌二醇-5,50,100,150组。除假手术组外,其余大鼠均建立去卵巢动物模型。葛根素-50组大鼠皮下注射葛根素50mg/kg,1次/d;雌二醇-200组大鼠皮下注射雌二醇200μg/kg,2次/周;葛根素+雌二醇-5,50,100,150组大鼠皮下注射葛根素25mg/kg,1次/d同时分别注射雌二醇5,50,100,150μg/kg,2次/周。结果与结论:去卵巢模型组大鼠骨密度和骨钙、骨磷水平明显低于假手术组(P<0.05),骨组织呈骨质疏松的病理改变;葛根素和/或雌二醇治疗10,20周后骨密度和骨钙、骨磷水平明显升高(P<0.05),其中葛根素+雌二醇-100组治疗去卵巢大鼠骨质疏松的效果最为明显,提示葛根素25mg/kg,1次/d+雌二醇100μg/kg,2次/周是治疗去卵巢大鼠骨质疏松的最佳搭配剂量。     

葛根素联合雌二醇对去卵巢大鼠骨质疏松症的治疗作用

背景:雌激素治疗绝经后骨质疏松症产生的不良反应较大.目的:观察小剂量葛根素联合雌二醇对去卵巢大鼠骨组织的影响.方法:120 只健康雌性大白鼠等分成只切除卵巢旁的一小块脂肪垫的假手术组和切除双侧卵巢的去卵巢模型组、葛根素组、雌二醇组及葛根素+雌二醇组.1 周后葛根素组、雌二醇组和雌二醇+葛根素组分别皮下注射葛根素(50 mg/kg,1 次/d)、雌二醇(200 μg/kg,2 次/周)和雌二醇(100 μg/kg,2 次/周)+葛根素(25 mg/kg,1 次/d).结果与结论:去卵巢模型组大鼠骨组织稀疏,骨钙、磷水平和骨密度明显低于假手术组(P < 0.01),而经雌二醇和/或葛根素治疗后大鼠骨组织形态明显改善、骨钙、磷水平和骨密度明显升高.其中小剂量的葛根素联合雌二醇治疗与较大剂量的葛根素或雌二醇治疗效果接近.提示较小剂量的雌二醇与葛根素联合治疗也可对去卵巢大鼠骨质疏松症产生良好的治疗效果.     

Sex differences in severity of inflammation-induced anorexia and weight loss

Food intake and body weight changes in response to induction of acute inflammation were examined in intact cycling females, ovariectomized females, and sham-operated male rats. In intact females, body weight and feeding responses were compared between rats in which inflammation was induced on day of estrus with rats in which inflammation was induced on day of diestrus. Anorexia and weight loss were more severe in the female rats with inflammation induced on estrus day, which coincides with peak serum estrogen levels. In ovariectomized females, inflammation was induced the day after rats received injections of estrogen, progesterone, or sesame oil (vehicle). Males received vehicle injections. Among female rats, the group that received estradiol injections the previous day displayed the most severe anorexia. The least severe anorexia was observed in female rats that received progesterone the previous day. Food intake of female rats that received vehicle injections prior to induction of inflammation was greater than the rats receiving estrogen but less than the rats receiving progesterone. Male rats displayed the most severe anorexia and greatest weight loss. These data suggest that, although females exposed to estradiol prior to induction of acute inflammation display more severe anorexia than those exposed to progesterone, it may be that progesterone attenuates severity of anorexia rather than estrogen solely potentiating severity. Male rats, however, appear to experience the most severe anorexia in response to this form of inflammation.     

Modulatory effects of estrogen and progesterone on colorectal hyperalgesia in the rat

The contribution of estrogen and progesterone to colorectal hyperalgesia was examined in female rats. The electromyogram recorded from the abdominal wall (visceromotor response, vmr) and the discharge of lumbosacral dorsal horn neurons to colorectal distention (CRD) were measured in intact female, ovariectomized (OVx) and estradiol replaced OVx (E2; 50mug, 48h) rats with and without colonic inflammation. Colorectal hyperalgesia was transient in intact rats, but persisted at least 4h in E2 and OVx rats. The magnitude of hyperalgesia in E2 rats was greater than OVx which was greater than intact rats. Dorsal horn neurons that responded to CRD with an Abrupt (on and off with stimulus) excitatory discharge showed similar sensitivity to estradiol as the vmr following colonic inflammation. In contrast, inflammation did not increase the magnitude of response of excitatory neurons with sustained afterdischarges in any of the treatment groups. Intact female rats have a comparable plasma estrogen concentration to E2 rats, suggesting the difference in responses may have been due to antinociceptive effects of progesterone. This was tested by administering E2+/- progesterone (1mg) and measuring the vmr. Progesterone reduced the facilitation of the vmr produced by E2 before and following colonic inflammation. The present study suggests that estrogen replacement enhances visceral signal processing following colonic inflammation. Furthermore, progesterone may counteract the effects of estrogen on colorectal sensitivity.     

Gender differences in ethanol preference and ingestion in rats. The role of the gonadal steroid environment.

An ethanol oral self administration paradigm showed the existence of gender differences in alcohol preference in rats: whereas males and females initiated alcohol drinking at similar rates, females maintained their preference for ethanol over a longer duration. Neonatal estrogenization of females, which effectively confers a male phenotype on a genetically female brain, resulted in patterns of drinking that were similar to those displayed by intact male rats, indicating that gender differences in alcohol drinking patterns may be, at least partially, accounted for by sexual differentiation of the brain. To test whether gonadal steroids also exert activational effects on ethanol-seeking behavior, we also examined the effects of gonadectomy alone, or in combination with gonadal steroid replacement therapy. Castration did not significantly alter ethanol consumption in males, although treatment of castrated rats with dihydrotestosterone resulted in a significant inhibition of this parameter. As compared with the situation in intact female rats, ethanol ingestion was significantly reduced in ovariectomized female rats receiving estradiol (E2) and in ovariectomized female rats receiving combined E2 and progesterone replacement therapy. However, neither ovariectomy nor progesterone replacement in ovariectomized rats resulted in ethanol drinking patterns that were different compared to those observed in intact female controls. Thus, dihydrotestosterone and E2, respectively, appear to exert modulatory influences on the male and female rats' preference for ethanol, but further investigations are necessary to determine to what extent these effects result from activational actions on the brain.     

Female gonadal hormones differentially modulate cocaine-induced behavioral sensitization in Fischer, Lewis, and Sprague-Dawley rats

Evidence suggests the existence of genetic differences in cocaine sensitization in male rats. The present study was undertaken to investigate cocaine sensitization in female rats of genetically distinct inbred (Fischer 344 and Lewis) and outbred (Sprague-Dawley) strains. All female rats were bilaterally ovariectomized and randomly assigned to one of four experimental groups: 1) estradiol benzoate group, 2) progesterone group, 3) estradiol benzoate-plus-progesterone group, and 4) ovariectomized group. Additional controls included sham-operated female rats, female rats that received a single oil injection, and female rats that received repeated oil injections. To determine gender-related differences in the acute and chronic effects of cocaine, data obtained from female rats were compared with those from strain- and weight-matched male rats. Estradiol benzoate-plus-progesterone female rats showed greater locomotor effect in response to an acute dose of cocaine and had more robust sensitization in response to repeated cocaine than did male rats. The bilateral removal of ovaries abolished cocaine sensitization. In all strains of rats studied, progesterone alone did not alter the ovariectomy-induced attenuation of cocaine behavior, but estrogen alone restored cocaine-induced behavioral sensitization. There were significant strain effects on the degree of gonadal hormonal-induced modulation of cocaine sensitization in female rats. Female Lewis rats were extremely sensitive to repeated-cocaine effects, whereas the Fischer 344 female rats showed only marginal effects. The Sprague-Dawley rats ranked intermediate in their behavioral sensitivity. The present study strongly supports the hypothesis that female rats are more sensitive to both acute and chronic behavioral effects of cocaine than are male rats and that the effects are strain dependent. It also shows that estrogen plays an important role in the increased sensitivity of female rats to cocaine sensitization. Together, these data indicate significant interactions between ovarian steroid hormones and genetic factors in cocaine-induced behavioral effects.     

麻黄对去卵巢肥胖大鼠体质量、血脂、血糖及激素水平的影响

背景近年来,中药麻黄用于肥胖症的治疗并有一定的效果,但麻黄对围绝经期妇女的肥胖是否有效有待研究.目的观察口服麻黄水煎剂对去卵巢肥胖大鼠体质量、血脂、血糖及激素水平的影响.设计完全随机分组设计,对照实验.单位兰州大学基础医学院生理学和心理学研究所.材料实验于2006-02/06在甘肃省新药临床前研究重点实验室和兰州大学基础医学院生理学和心理学研究所实验室完成.选用健康雌性SD大鼠44只,随机分为4组,每组11只,分别为假手术组,去卵巢组,雌激素替代治疗组和麻黄组.方法①大鼠用氯胺酮(110 mg/kg)麻醉,除假手术组外全部行双侧去卵巢术.假手术组进行同样的手术过程,但不切除卵巢.②假手术组和去卵巢组大鼠术后每天皮下注射芝麻油(0.2 mL/只),持续到实验结束.③雌激素替代治疗组大鼠术后每天皮下注射雌激素(1 mg/kg),持续到实验结束.④麻黄组大鼠术后自然口服1%浓度的麻黄水煎剂,到第6天浓度逐渐增至8%,持续到实验结束.⑤每天测定大鼠的摄食量,每隔10天测定大鼠的体质量.⑥实验结束时,所有实验动物禁食12 h后,颈动脉取血测定血清指标.同时测定体质量和体长计算李氏指数[(g)×103/体长(cm)].主要观察指标①不同时间点各组大鼠体质量及李氏指数.②不同时间点各组大鼠摄食量结果.③大鼠血脂和血糖水平.④不同组别大鼠血清雌激素、孕激素和胰岛素水平. 结果大鼠44只全部进入结果分析.①不同时间点各组大鼠体质量及李氏指数结果去卵巢组大鼠实验开始第20,30,40,50天体质量分别为(256.4±14.3),(271.3±16.1),(276.4±12.7),(285.7±24.2)g,均大于假手术组大鼠相应时间点[(226.5±11.5),(241.8±12.6),(243.1±13.5),(251.1±22.4)g,P＜0.05～0.01],李氏指数大于假手术组(317.2±13.5,280.4±11.2,P＜0.01).雌激素替代治疗组实验开始第40,50天体质量分别为(243.7±14.8),(246.2±11.9)g,低于去卵巢组相应时间点(P＜0.05～0.01),李氏指数为289.9±13.5,小于去卵巢组(P＜0.01).麻黄组大鼠实验开始第40,50天体质量分别为(245.4±14.1),(252.4±14.9)g,李氏指数为294.4±11.0,小于去卵巢组(P＜0.05).②不同时间点各组大鼠摄食量结果麻黄组大鼠实验开始第30,40,50天摄食量分别为(17.8±2.4),(22.3±3.9),(26.1±3.5)g/d,与去卵巢组比减少[(25.9±4.7),(28.5±5.3),(32.8±5.5)g/d,P＜0.05].③大鼠血脂和血糖水平去卵巢组大鼠血清三酰甘油、胆固醇、低密度脂蛋白胆固醇含量分别为(1.73±0.32),(1.45±0.50),(0.78±0.19)mmol/L,高于假手术组[(0.94±0.29),(1.05±0.30),(0.08±0.11)mmol/L,P＜0.01].雌激素替代治疗后三酰甘油、胆固醇、低密度脂蛋白胆固醇含量及血糖浓度分别为(1.10±0.34),(1.14±0.30),(0.17±0.05),(5.88±1.21)mmol/L,低于去卵巢组(P＜0.05～0.01),高密度脂蛋白胆固醇含量高于去卵巢组[(1.11±0.31),(0.88±0.21)mmol/L,P＜0.05].麻黄组三酰甘油、胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇含量分别为(0.97±0.16),(1.11±0.20),(0.59±0.07),(0.45±0.061)mmol/L,低与去卵巢组(P＜0.05～0.01).④不同组别大鼠血清雌激素、孕激素和胰岛素水平去卵巢组大鼠雌激素、孕激素水平分别为(17.09±9.00)ng/L,(28.51±7.99)μg/L,低于假手术组[(58.69±12.11)ng/L,(62.73±10.93)μg/L,P＜0.01],胰岛素含量高于假手术组[(31.74±6.69),(23.75±6.66)mU/L,P＜0.01].雌激素替代治疗组及和麻黄组雌激素水平为(36.03±8.83),(30.18±8.61)ng/L,高于去卵巢组(P＜0.05～0.01),胰岛素水平分别为(21.34±4.57),(24.86±6.20)mU/L,低于去卵巢组(P＜0.05～0.01),麻黄组孕激素水平为(17.68±6.19)μg/L,低于去卵巢组(P＜0.01).结论麻黄能明显降低去卵巢肥胖大鼠的体质量,降低血脂和胰岛素水平,增加血中雌激素水平.     

Ovarian steroid hormone modulation of the acute effects of cocaine on luteinizing hormone and prolactin levels in ovariectomized rhesus monkeys

Cocaine stimulates significant increases in luteinizing hormone (LH) and decreases prolactin levels in gonadally intact rhesus monkeys, but cocaine did not alter plasma levels of these anterior pituitary hormones in ovariectomized females. These findings suggested that ovarian steroid hormones may contribute to the endocrine effects of acute cocaine administration. To test this hypothesis, the acute effects of cocaine and placebo-cocaine on plasma LH and prolactin levels were examined in five ovariectomized rhesus females during three chronic hormone replacement conditions: 1) estradiol (E2beta) treatment (0.0015-0.006 mg/kg/day i.m.), 2) progesterone treatment (0.32 mg/kg/day i.m.), and 3) combinations of progesterone (0.32 mg/kg/day i.m.) and E2beta (0.002 and 0.004 mg/kg/day i.m.). Cocaine (0.8 mg/kg i.v.) did not alter prolactin or LH in ovariectomized monkeys without ovarian steroid replacement. During chronic estradiol treatment, cocaine produced an estradiol dose-dependent decrease in prolactin. Cocaine also decreased prolactin during treatment with progesterone alone and progesterone + E2beta (0.004 mg/kg/day i.m.). Cocaine stimulated a significant increase in LH during treatment with progesterone alone, but not during treatment with progesterone + E2beta, or three of four estradiol treatment doses. Cocaine pharmacokinetics did not differ as a function of hormone replacement conditions. Together, these data suggest that both E2beta and progesterone modulate cocaine's effects on prolactin, whereas E2beta alone and in combination with progesterone, do not facilitate LH release in response to cocaine in ovariectomized rhesus females.     

三种子宫内膜增生大鼠模型的建立和评价

目的探讨子宫内膜增生大鼠模型的建立方法和评价体系。方法SD雌性大鼠60只,随机平均分为假手术组(A组)、去势组(B组)、雌激素负荷组(C组)、去势联合雌激素负荷组(D组)。B组和D组大鼠摘除双侧卵巢后第3天起分别以0.15 mL/100 g肌内注射高压灭菌麻油和1 mg/mL以高压灭菌麻油稀释的苯甲酸雌二醇注射液;C组仅以同剂量肌肉注射1 mg/mL以高压灭菌麻油稀释的苯甲酸雌二醇注射液;A组仅行开关大鼠腹部手术,同法同剂量注射高压灭菌麻油;均隔1天1次,共14次。采用吉姆萨阴道涂片染色法剔除B、D组有角化现象的大鼠。在末次注射24 h后,处死各组大鼠采集血清、子宫,采用ELISA检测血清中雌激素(E2)、泌乳素(prol)、孕激素(P)、黄体生成素(LH)和卵泡刺激素(FSH)水平,HE染色法观察子宫形态、内膜厚度和面积。结果与A组比较:B组大鼠prol、LH和FSH明显升高,而E2、P明显降低;C组大鼠E2、LH和FSH明显升高(P<0.05),而P明显降低(P<0.05);D组大鼠prol、LH和FSH明显升高(P<0.05),而E2、P明显降低(P<0.05)。B、C、D 3组大鼠均出现了明显的子宫内膜萎缩,腺体增多,肌层变薄,肌纤维排列紊乱的现象,C组和D组子宫内膜可见嗜酸性粒细胞浸润。结论采用去势法、雌激素负荷法及两者联合的方法均可较好地诱导子宫内膜腺体增生大鼠模型;采用雌激素负荷法和去势联合雌激素负荷所建立的模型具有子宫内膜炎性增厚的特征。     

葛根异黄酮联合维生素D防治骨质疏松的协同效应

背景:葛根异黄酮具有类雌二醇结构特征,对去卵巢大鼠的骨质丢失和骨量的减少有一定的抑制作用.但也有报道其对去卵巢大鼠骨质疏松的防治效果较弱且单独使用效果不明显.目的:观察葛根异黄酮与维生素D联合对去卵巢大鼠骨质疏松的作用.方法:将81只3月龄雌性SD大鼠随机分为9组:除假手术组外其他各组均行双侧卵巢摘除造模.低、中、高剂量TIP组,VitD组,低、中、高剂量联合组在去卵巢基础上分别灌胃给予相应剂量的葛根异黄酮和(或)维生素D;模型组和假手术组不给予药物治疗.给药3个月,计算大鼠子宫系数;测定大鼠血清碱性磷酸酶、血钙、血磷、骨钙素及血清雌二醇水平;检测大鼠股骨骨密度.结果与结论:与模型组比较,中、高剂量TIP组,低、中、高剂量联合组大鼠子宫系数、雌二醇水平明显增高(P < 0.05),血清碱性磷酸酶、骨钙素水平明显降低(P < 0.05),股骨中心及远心骨密度均明显增加(P < 0.05),均以高剂量联合组作用效果最明显.且在子宫系数,雌二醇、血清碱性磷酸酶、骨钙素水平及股骨远心端骨密度方面,葛根异黄酮和维生素D均表现为协同作用.在血钙、血磷方面,葛根异黄酮和(或)维生素D的作用不明显.说明葛根异黄酮和维生素D联合使用对去卵巢大鼠骨质疏松的防治有协同效应.