雌激素替代治疗对去势大鼠阴道组织雌激素受体表达的影响

目的 研究雌激素对去势大鼠阴道组织ERα与ERβ表达的影响，探讨雌激素治疗老年性阴道炎的分子机制。方法将40只雌性SD大鼠随机分成对照组、假手术组、去势组和雌激素替代治疗组各10只。对照组为空白对照；假手术组去除卵巢周围与卵巢相同大小脂肪组织；去势组行双侧卵巢切除术；雌激素替代治疗组在去卵巢手术3周后行戊酸雌二醇800 μg•kg 1•d 1替代治疗8周。免疫组织化学染色检测大鼠阴道组织ERα与ERβ表达情况。结果去势组大鼠ERα、ERβ表达显著低于对照组（均P＜0.01），雌激素替代组ERα、ERβ表达上升，较去势组显著增强（均P＜0.01）。结论雌激素替代治疗可导致雌激素受体表达上升，可能导致雌激素受体效应增强，从而提高阴道局部抵抗力。     

鹿瓜多肽注射液对去卵巢大鼠骨密度及松质骨中骨形态发生蛋白表达的影响

目的探讨鹿瓜多肽（松梅乐）注射液肌肉注射对去卵巢大鼠骨密度及松质骨中骨形态发生蛋白（BMP2）表达的影响。方法将8月龄未经产雌性二级SD大鼠30只，随机分为假手术（SHAM）组、去势（VOX）组、去势＋鹿瓜多肽（VOX＋SML）组。VOX＋SML组大鼠术后第2天开始给药。术后20周处死各组大鼠，对各组大鼠骨密度进行检测。利用免疫组织化学染色及图像分析方法对各组大鼠松质骨切片图像进行灰度分析，观察鹿瓜多肽注射对去势大鼠腰椎松质骨中BMP2表达的影响。结果①去势组与SHAM组相比较，灰度值降低。而（VOX＋SML）治疗组较VOX组灰度值降低，表明VOX大鼠松质骨中骨小梁周围厦髓腔内BMP：表迭阳性细胞数明显多于SHAM组；而（VOX＋SML）治疗组骨小梁周围及髓腔内BMP2表达阳性细胞数多于VOX组，且染色加深。②与SHAM组相比，VOX组股骨近端、股骨干、腰椎的骨密度明显降低（P〈0．01）；（VOX＋SML）治疗组各部位的骨密度高于VOX组（P〈0．05），但未达到SHAM组水平（P〉0．05）。结论鹿瓜多肽注射液可抑制和延缓骨质疏松形成，对雌激素缺乏引起的骨质疏松具有预防作用。     

骨金散对去卵巢大鼠骨密度、雌激素水平的影响

目的:复制去卵巢大鼠骨质疏松的动物模型,探讨中药骨金散对去卵巢雌性大鼠雌激素和骨密度的影响.方法:6月龄雌性SD大鼠40只,随机分为去势组和假手术组.去势组切除双侧卵巢,假手术组切除部分脂肪.大鼠去势后1个月,将去势组随机分为3组:模型组、雌激素组和骨金散组,雌激素组每日灌服己烯雌酚0.05mg/kg,骨金散组按1.8...     

骨金散对去卵巢大鼠Ⅰ型胶原交联N-端肽、Ⅰ型胶原mRNA表达的影响

目的：复制去卵巢大鼠骨质疏松动物模型,探讨中药骨金散对去卵巢雌性大鼠血清Ⅰ型胶原交联N-端肽（NTX）和骨组织Ⅰ型胶原mRNA表达的影响。方法：6月龄雌性SD大鼠40只,随机分为去势组和假手术组。去势组切除双侧卵巢,假手术组切除部分脂肪。大鼠去势后1个月,将去势组随机分为3组：模型组、雌激素组和骨金散组,雌激素组每日灌服己烯雌酚0.05m g/kg,骨金散组按1.8g/kg剂量灌服骨金散,其余各组灌服等量生理盐水。2个月后,酶联免疫吸附法测量血清碱性磷酸酶（ALP）、NTX水平,RT-PCR方法检测右侧股骨骨组织Ⅰ型胶原mRNA表达水平。结果：与假手术组比较,模型组血清ALP、NTX含量明显升高（P〈0.01）,Ⅰ型胶原mRNA水平显著下降（P〈0.01）。雌激素组和骨金散组大鼠体内的ALP、NTX水平显著低于模型组（P〈0.01）,骨金散组大鼠体内的ALP水平高于雌激素组（P〈0.05）。雌激素组和骨金散组实验大鼠骨组织中Ⅰ型胶原蛋白mRNA表达含量明显高于模型组（P〈0.01）。结论：骨金散可减轻去卵巢大鼠ALP、NTX水平的提高,上调骨组织Ⅰ型胶原mRNA的表达水平,这可能与其治疗骨质疏松的机制有关。     

大豆黄酮对去势大鼠心血管保护作用的研究

目的：动物实验观察大豆黄,酮对去势大鼠心血管的保护作用，并初探讨其机制。方法：将60只雌性大鼠随机分为3组：（1）去势组，（P组，n=20)；（2）去势＋大豆黄酮治疗组（D组，n=20)，（3）假手术组，（C组，n=20)，分别于术前，术后或治疗后采血测定血脂水平，雌二醇（E2），一氧化氮NO，内皮素（ET－1）。结果：去势后，血脂水平升高，E2降低，NO降低，ET－升高（P＜0．05），大豆黄酮治疗后，E2，血脂水平，NO恢复（P＞0．05），ET－1降低。结论：大豆黄酮通过恢复去势大鼠雌激素水平而使血脂水平恢复正常，并可升高NO，降低ET－1，改善内皮功能，从而达到防治冠心病发生发展的目的。     

雌激素水平对肾血管性高血压大鼠肾功能及氧化应激的影响

目的研究雌激素水平对肾血管性高血压大鼠肾功能及氧化应激的影响。方法取10周龄雌性Sprague-Dawley (SD)大鼠,狭窄一侧肾动脉建立肾血管性高血压模型,雌性高血压大鼠切除双侧卵巢建立雌激素低下模型,去势高血压大鼠补充雌二醇建立雌激素治疗组。将其随机分为雌性假手术组、雌性手术组、雌性手术去势组和雌激素治疗组。手术32周后进行颈动脉插管测定收缩压,全自动生化仪测定血清中的尿素氮(BUN)和血肌酐(Scr)水平;WST-1法测定肾脏组织中的超氧化物歧化酶(SOD)水平;TBA法测定肾脏组织中的丙二醛(MDA)水平。结果雌激素治疗组Scr水平明显高于假手术组、雌性手术组和雌性手术去势组(P<0.05);与假手术组和雌性手术去势组比较,雌激素治疗组BUN水平显著升高(P<0.01)。雌激素治疗组SOD水平明显低于假手术组和雌性手术去势组(P<0.05,P<0.01),MDA水平明显升高(P<0.05)。结论雌性肾血管性高血压大鼠切除双侧卵巢致雌激素水平低下后,补充雌激素治疗可加重肾血管性高血压大鼠肾功能损伤程度和氧化应激水平。     

细胞因子与骨质疏松的实验研究

目的 探讨细胞因子白细胞介素－6（IL－6）和肿瘤坏死因子（TNF）与骨质疏松发生的关系。方法 以去势后雌性SD大鼠为模型,分去势组、假手术组和去热加利维爱组,共三组,对照研究骨密度（BMD）和骨髓微环境中IL－6和TNF的含量变化。结果 骨髓单核细胞具有分泌TNF和IL－6作用;卵巢分不必性激素水平下降可导致骨髓单核细胞TNF和IL－6基因表达调节失控;去势后大鼠体内TNF和IL－6水平与BMD呈负相关。结论 提示TNF和IL－6的水平升高是引起骨丢失的机理之一,卵巢分泌性激素对TNF和IL－6具有下调作用。     

阿仑膦酸钠联合辛伐他汀对骨质疏松骨折的影响

目的通过实验观察阿仑膦酸钠联合辛伐他汀对骨质疏松大鼠骨折愈合的影响。方法成年雌性SD大鼠50只,随机分为5组：（A）假手术对照组;（B）去势对照组;（C）去势阿仑膦酸钠组;（D）去势辛伐他汀组;（E）去势联合用药组。B、C、D、E组行双侧卵巢切除术,A组仅切除部分脂肪组织。8周后每组随机选取2只大鼠确认骨质疏松造模成功后,各组均行左侧股骨中段骨折,并使用克氏针髓内固定。骨折内固定术后予以下药物干预：A、B两组：生理盐水5mL／（kg·d）灌胃8周;C组：阿仑膦酸钠0．5mg／（kg·d）灌胃8周;D组：辛伐他汀20mg／（kg·d）灌胃8周;E组阿仑膦酸钠0．5mg/（kg·d）＋辛伐他汀20mg／（kg·d）灌胃8周。所有大鼠处死后收集血样和左侧股骨,进行血钙、磷、碱性磷酸酶含量、股骨X线骨密度及生物力学强度检测。结果卵巢去势组对比假手术对照组骨密度有明显减少,血清碱性磷酸酶水平升高,血钙、磷变化无统计学意义;使用阿仑膦酸钠及联合辛伐他汀治疗8周后,血钙、磷变化无统计学意义,碱性磷酸酶降低,股骨骨密度、生物力学功能获得改善,其中联合用药组更为明显,差异有统计学意义。结论阿仑膦酸钠有助于骨质疏松骨折愈合后生物力学功能的恢复,其中辛伐他汀可起到协同作用。     

雌激素对卵巢切除后雌性大鼠心肌组织中雌激素受体表达的影响

目的：探讨雌激素对卵巢切除后雌性大鼠心肌组织中雌激素受体表达的影响。方法：雌性SD大鼠卵巢切除术（OVX）后1周,随机分成3组：OVX＋雌激素（0.15mg/kg,s.c.）、OVX＋生理盐水、对照组。4周后,Westernblotting检测α和β两种雌激素受体在心肌组织中的表达。结果：卵巢切除后,血清雌激素水平与对照组[（88±22vs403±59）pmol/L,P〈0.05]相比明显下降,左心室肌中两种雌激素受体表达均下降（P〈0.05）。给予雌激素后,血清雌激素水平上升为（3864±105）pmol/L,雌激素β受体表达增多（P〈0.05）,α受体表达下降（P〈0.05）。结论：雌激素改变卵巢切除后雌性大鼠心肌组织中雌激素受体的表达。     

刺芒柄花素对去势大鼠主动脉弓雌激素受体β表达的影响

目的:研究植物雌激素刺芒柄花素对去卵巢+高脂血症大鼠主动脉弓雌激素受体β(ERβ)表达的影响以了解刺芒柄花素对去势大鼠心血管的保护作用。方法:实验选取SD大鼠制作去势高脂模型,以Western blot和real-timePCR方法检测主动脉弓中ERβ的含量。结果:Western blot结果表明模型组大鼠主动脉弓ERβ的含量较假手术组明显减少,尼尔雌醇组和高剂量刺芒柄花素组较模型组明显升高(P<0.05),低剂量刺芒柄花素组较模型组也升高,但两者差异无统计学意义。real-time结果显示尼尔雌醇组ERβ含量最高,高剂量刺芒柄花素组次之,低剂量略低,模型组大鼠ERβ含量最低。结论:雌激素水平降低可使大鼠主动脉血管雌激素受体β表达减少,合适剂量的刺芒柄花素能上调去势大鼠主动脉血管ERβ的表达     

Estrogen regulates responses of dopamine neurons in the ventral tegmental area to cocaine

RATIONALE: Sex differences in cocaine abuse have been well documented. However, the underlying mechanism remains unclear. OBJECTIVES: To explore the potential role of ovarian hormones in the regulation of dopamine (DA) neuron firing activity in ventral tegmental area (VTA) induced by acute cocaine in intact female or ovariectomized (OVX) rats. RESULTS: The basal firing activity of VTA DA neurons was changed in a manner phase-locked to the estrous cycle: being highest in estrus and lowest in proestrus. Acute cocaine produced greater inhibition (P < 0.05) on the firing of VTA DA neurons during proestrus than during estrus. The inhibitory effect was completely blocked by OVX and restored by replacement of 17-beta-estradiol or, to a less extent, by replacement of progesterone. In addition, we also detected female hormone-associated changes in slow oscillation in VTA DA neurons. The results indicate that ovarian hormones, particularly estrogen, not only synergize with the inhibitory effect of cocaine on VTA DA neuron activity but also play an essential role in maintaining the sensitivity of DA neurons to cocaine-mediated inhibition on firing. Moreover, pretreatment of estrogen receptor (ER) antagonist raloxifene or a selective ERalpha antagonist Y134 largely attenuated the cocaine-inhibited DA neuron firing. We also found that cocaine-induced locomotor activity was estrous cycle dependent; 17-beta-estradiol but not progesterone replacement restored the cocaine-induced locomotor activity in OVX rats. CONCLUSION: The present results demonstrated that ovarian hormones, particularly estrogen, produce profound effect on VTA DA neuron activity, which, in turn, may contribute to the sex differences in response to psychostimulants.     

Estrogen attenuates cardiac ischemia-reperfusion injury via inhibition of calpain-mediated bid cleavage

Although several studies have shown that the administration of 17beta-estradiol (estrogen) is cardioprotective to ischemia-reperfusion (I/R), the molecular mechanisms are largely unknown. Therefore, we investigated the effects of estrogen on myocardial I/R injury in rat that were sham operated (Sham), ovariectomized (OVX), or ovariectomized and then given estrogen supplementation (OE). Langendorff-perfused rat hearts were subjected to I/R stimuli and the effects of estrogen were examined on cardiac performance. Additionally, we examined the mechanism of estrogen-mediated inhibition of apoptosis. Depression in cardiac contractile function and an increment of calpain activity were observed during I/R in the OVX rats. Estrogen replacement recovered cardiac contractile function and attenuated calpain activity, Bid cleavage, and caspases activities. Through in vitro assay using cardiomyocytes, we demonstrated that addition of H2O2 (100 microM) significantly increased calpain activity, which was attenuated by estrogen. Moreover, calpain activity was inhibited by calpain inhibitors such as ALLN or leupeptin, but not by caspase-8 inhibitor peptide. These results suggest that estrogen protects the heart against I/R injury through the decrease of calpain activity, Bid cleavage and caspase-8 activity. These apoptotic mechanisms may play a critical role on I/R-associated cardiac damage.     

雌激素孕激素及受体在肝门部胆管癌中的表达

目的探讨雌、孕激素(ER、PR)及其受体在肝门部胆管癌的发生中的作用。方法应用放射免疫法测定42例肝门部胆管癌患者血中的雌、孕激素水平；应用免疫组织化学法，检测其组织中ER及PR表达水平。结果42例肝门部胆管癌患者中，雌、孕激素高于正常者分别占73．8％和69．0％，ER及PR阳性表达率分别为66．7％、和64．3％。与对照组相比，雌、孕激素水平及受体表达具有明显差异。结论肝门部胆管癌患者中，多数雌、孕激素水平高，ER及PR表达率高。雌、孕激素及受体可能在肝门部胆管癌发生和发展过程中起重要作用。     

Effects of ginkgo biloba on <Emphasis Type="Italic">in vitro</Emphasis> osteoblast cells and ovariectomized rat osteoclast cells

Ginkgo biloba extract (GBE) has a selective estrogen receptor modulator (SERM)-like biphasic effect on estrogen, and could be a potential alternative to hormone replacement therapy (HRT). Here, we investigated whether GBE can ameliorate estrogen-depleted osteoporosis in in vitro osteoblast cells and in estrogen-deprived ovariectomized (OVX) rats, a classical animal model for postmenopausal osteoporosis. GBE (50–150 μg/mL) significantly increased ALP (Alkaline phosphatase) activity of osteoblast cells, indicating that GBE promotes osteoblast mineralization. OVX rats exposed to GBE (100 and 200 mg/kg/day, oral treatment), raloxifene (3 mg/kg/day, oral treatment) or estradiol (E₂, 10 μg/kg/day, subcutaneous injection) decreased osteoclast resorptive activity compared with OVX rats. GBE and raloxifene did not increase uterine weight compared with OVX rats, while E₂ and Sham control did, suggesting that GBE has no uterotrophic activity, which is a disadvantage of estrogen therapy. In OVX rats, GBE did not restore severe bone density loss induced by OVX, indicating that GBE may be insufficient as therapeutic material for severe osteoporosis. However, despite its no effects on bone density loss in OVX rats, GBE did stimulate osteoblast differentiation and antiosteoclastic activity in vitro. Therefore, GBE may have preventive potential on osteoporosis as do other phytoestrogens.     

Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1-16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE₂) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS_PE and BRS_SNP). Nicotine (100 μg/kg i.v.) reduced BRS_SNP in OVX rats but not in proestrus or OVXE₂ rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS_PE was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine-BRS_SNP interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS_SNP attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E₂ against nicotine-induced baroreceptor dysfunction in female rats.     

选择性雌激素受体调节剂的研究与开发

分类综述近年来非甾体类选择性雌激素受体调节剂(SERMs)的研究与开发,其中包括三苯乙烯类、苯并噻吩类、吲哚类、萘类、苯并吡喃类、呋喃类、吡唑类、四环类等。SERMs是在某些组织中具有激动作用、而在另一些组织中具有拮抗作用的一类化合物,它们可避免或减少雌激素替代疗法所产生的副作用。     

血腑逐瘀汤对子宫肌瘤雌激素受体和BCL-2 表达的影响

目的探讨血腑逐瘀汤对子宫肌瘤雌激素受体、BCL-2表达的影响及其作用机制。方法采用肌注雌激素法造模,把SD大鼠随机分成对照组、模型对照组、低剂量组、中剂量组和高剂量组,用免疫组化法测定大鼠子宫内膜中ER含量以及凋亡基因Bcl-2蛋白的表达。结果随着血腑逐瘀汤剂量的增大,大鼠子宫重量和大鼠子宫内膜ER含量明显降低;平滑肌Bcl-2蛋白表达明显增多(P<0.01)。结论血腑逐瘀汤可显著抑制子宫肌瘤雌激素受体的表达,同时可降低子宫肌瘤模型大鼠细胞凋亡蛋白Bcl-2阳性表达。     

子宫内膜癌雌孕激素受体检测的临床意义

目的:检测子宫内膜癌组织中雌激素受体(ER)、孕激素受体(PR)表达的阳性率并探讨其与预后的关系。方法:用免疫组化法对32例子宫内膜癌标本进行ER、PR的检测。结果:子宫内膜癌组织中ER、PR的阳性率分别为53.1%、50.0%。ER、PR的阳性表达率与癌组织的细胞分化程度有关,随着子宫内膜癌组织学分级的增高,ER、PR阳性率表达率逐渐降低,ER的表达还与肌层浸润深度有关。结论:ER、PR均反应了子宫内膜癌的生物学行为,其测定对预测临床预后、指导临床选择内分泌治疗具有重要意义。