尼尔雌醇影响OVX大鼠骨细胞IL—6 mRNA表达水平的研究

目的：研究尼尔雌醇对OVX大鼠IL－6 mRNA表达水平的影响,探讨绝经后骨质疏松的分子细胞学机制。方法：将30只3月龄雌性Wistar大鼠随机分成3组,每组10只,即OVX组、假手术组和尼尔雌醇组（雌醇组）。对OVX组和雌醇组行双侧卵巢切除制备绝经后骨质疏松模型,雌醇组于术后1周予尼尔雌醇治疗。3个月后处死全部实验动物,直接从骨组织中提取总RNA,采用相对半定量逆转录－聚合酶链反应（RT－PCR）技术检测IL－6 mRNA表达情况。结果：雌醇组IL－6mRNA水平显著低于OVX组（P＜0．01）,与假手术组相比无显著性差异（P＞0．05）。结论：IL－6参与调节雌激素撤退所致的骨吸收,尼尔雌醇可以抑制IL－6的基因表达,减少骨丢失,维持骨量。     

异普黄酮抗卵巢切除大鼠的骨质疏松与上调腰椎护骨素mRNA的表达

目的：制造绝经后骨质疏松（postamenopausal osteopomsis，PMOP）的大鼠动物模型，研究异普黄酮（Ipriflavone，Ip）对卵巢切除大鼠腰椎护骨素（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Sprague-Dawley大鼠4JD只，随机分为假手术组（Sham），卵巢切除组（OVX），OVX＋戊酸雌二醇组（E2）和OVX＋Ip组（Ip）。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组大鼠较假手术组骨小梁体积百分比（TBV％）显著下降；类骨质体积百分比（OSV％）明显升高（P〈0．05）；E2和Ip均可使OVX大鼠的TBV％明显升高，OSV％明显下降；OPG mRNA表达水平在OVX大鼠骨组织中下调，与假手术组相比有显著性差异（P〈0．05），E2和IP均可上调OVX大鼠骨组织OPG mRNA表达水平（P〈0．05）。结论：实验成功制造了大鼠PMOP模型；E2和Ip均通过抑制骨转换发挥预防和治疗PMOP的作用；PMOP的发生与OPG有关，Ip和E2一样，其预防和治疗骨吸收效应很可能是通过OPG介导的。     

骨质疏松性骨损伤愈合过程中细胞生长因子的动态表达

目的:从分子水平上探讨细胞生长因子转化生长因子-β1(TGF-β1)、碱性成纤维细胞生长因子(bFGF)在骨质疏松大鼠骨损伤愈合过程中的表达水平及其相互作用.方法:3月龄雌性大鼠64只,以去卵巢方法建立骨质疏松大鼠模型,分为骨质疏松组(OVX组)32只和假手术组(SX组)32只.运用实时荧光定量PCR检测TGF-β1、bFGF在OVX和SX组大鼠骨组织中的表达水平.结果:(1)OVX组和SX组组内骨损伤后不同时间点TGF-β1、bFGF表达水平的差别具有统计学意义(P<0.01).5d开始逐渐升高,15 d时达到高峰,30d时同落到低水平.(2)OVX组TGF-β1、bFGF mRNA的表达水平均低于同时期SX组的水平.结论:TGF-β1、bFGF在骨损伤后存在约4周的周期性表达,并且于骨质疏松性骨损伤处表达减少,这是其愈合质量下降的重要因素.TGF-β1、bFGF的表达趋势类似,提示它们之间可能存在某种协同作用.     

葛根异黄酮对去卵巢大鼠的抗骨质疏松作用及其机制

目的研究葛根异黄酮对去卵巢大鼠抗骨质疏松的作用机制。方法选择3月龄健康雌性Wister大鼠60只,随机分为假手术组、模型组、尼尔雌醇组、葛根异黄酮低、中和高剂量组等6组,每组10只。假手术和模型组灌胃给予0.5%CMC-Na溶液;尼尔雌醇组灌胃给予尼尔雌醇0.5 mg/kg,每周2次(周一和周四);葛根异黄酮低、中和高剂量组分别灌胃给予葛根异黄酮25,50,和100 mg/kg,时间均为70 d。采用ELISA法测定血清细胞因子IL-6、IGF-1水平;免疫组化法测定颅骨成骨细胞骨形态发生蛋白-2(BMP-2)的表达;双能X线骨密度仪测量股骨中点及远心端骨密度。结果葛根异黄酮能明显的增加股骨中点及远心端骨密度(P<0.05),升高血清IGF-1的水平(P<0.05),降低血清IL-6的水平(P<0.01),并且能较好的增加成骨细胞BMP-2表达水平(P<0.01)。结论葛根异黄酮能够改善骨质疏松,作用机制可能通过下调IL-6表达水平和提高成骨细胞BMP-2的表达实现的。     

雌激素类药物对去卵巢大鼠认知功能的影响

目的 研究雌激素类药物对去卵巢大鼠认知功能的影响.方法 48只3～5个月龄雌性SD大鼠(清洁级)随机分为8组:假手术组、去卵巢(OVX)组、去卵巢后7-甲基异炔诺酮治疗组、去卵巢后雷洛昔芬治疗组、去卵巢后戊酸雌二醇治疗组、去卵巢后大豆异黄酮治疗组、去卵巢后半量戊酸雌二醇+半量大豆异黄酮治疗组、去卵巢后半量戊酸雌二醇+全量大豆异黄酮治疗组,每组6只,用药3个月.做Morris水迷宫实验测定大鼠逃避潜伏期及运动策略以判断认知功能的变化,同时用RT-PCR方法检测大鼠脑部海马淀粉样蛋白前体(APP)mRNA水平.结果 OVX组逃避潜伏期明显长于假手术组.所有用药组逃避潜伏期时间明显短于OVX组;且用药组高级运动策略次数明显多于OVX组.大鼠去卵巢后.海马APP mRNA表达量明显增高,用药组及假手术组APPmRNA表达低于OVX组.结论 雌激素类药物能抵抗去卵巢大鼠认知功能的损害,且可能是通过下调去卵巢大鼠海马APP mRNA表达水平发挥作用的.     

绿原酸通过降低骨髓间充质干细胞凋亡抗绝经后骨质疏松的机制研究

目的 探讨绿原酸对绝经后骨质疏松（PMOP）大鼠的影响及其机制。方法 采用卵巢切除术构建PMOP大鼠模型,将建模成功大鼠分为去卵巢（OVX）组、绿原酸组、绿原酸+SB203580组,各10只;同时设置10只假手术组。比较各组大鼠骨密度,股骨骨微结构,血清雌二醇、碱性磷酸酶（ALP）水平,骨髓间充质干细胞（BMSCs）凋亡率,BMSCs中Runt相关转录因子2(Runx2)、锌指转录因子（Osterix）、ALP mRNA水平,BMSCs中p-p38MAPK/p38MAPK、Caspase3蛋白水平。结果 OVX组大鼠股骨内骨小梁大量缺失,骨密度、骨小梁数量、血清雌二醇、ALP水平、BMSCs中Runx2、Osterix、ALP mRNA水平、BMSCs中p-p38MAPK/p38MAPK蛋白水平低于假手术组,差异有统计学意义（P<0.05）;OVX组股骨骨小梁分离度、BMSCs凋亡率、Caspase3蛋白水平高于假手术组,差异有统计学意义（P<0.05）。绿原酸组大鼠股骨骨小梁基本恢复,骨密度、骨小梁数量、血清雌二醇、ALP水平、BMSCs中Runx2、Osterix、AL...     

蛇床子总黄酮对去卵巢骨质疏松大鼠股骨骨密度及生物力学的影响

目的探讨蛇床子总黄酮对去卵巢（OVX）骨质疏松大鼠股骨骨密度及股骨生物力学的影响。方法40只6、7月龄雌性SD大鼠随机分为4组：假手术（SHAM）组,去卵巢（OVX）组,OVX＋已烯雌酚（E）组和OVX＋蛇床子总黄酮组,每组10只。实行手术后,于术后第三天开始灌胃用药。90天后处死大鼠,取左测股骨进行股骨骨密度和股骨生物力学的测量。结果去卵巢后股骨骨密度及股骨生物力学指标明显下降;用蛇床子总黄酮后,股骨骨密度及股骨生物力学指标均增高。结论蛇床子总黄酮对去卵巢（OVX）造成的骨质疏松有一定的防治作用,能防止骨生物力学性能的受损,效果略逊色于已烯雌酚。     

大豆异黄酮对去卵巢大鼠骨密度和雌激素活性的影响(英文)

目的 :研究大豆异黄酮对去卵巢大鼠骨密度以及雌激素活性的影响。方法 :将 10～ 12月龄的雌性Wistar大鼠随机分为 6组 :假手术组 (SHAM )、切卵巢模型组 (OVX)、尼尔雌醇组 (OVX E)、小剂量异黄酮组 (L ISO)、中剂量异黄酮组 (M ISO)、大剂量异黄酮组 (H ISO) ,每组 8只。后 5组大鼠被切除双侧卵巢 ,SHAM组只被切除卵巢附近脂肪组织。L ISO ,M ISO ,H ISO分别灌胃给予 30 ,6 0 ,12 0mg·kg- 1的大豆异黄酮 ,OVX E组大鼠灌胃给予0 .2mg·kg- 1·wk- 1的尼尔雌醇 ,SHAM与OVX组以等剂量的溶剂灌胃 ,15wk后股动脉放血处死动物 ,收集血液用于血清碱性磷酸酶活性、血清雌二醇水平、血钙、血磷测定 ,分离出右侧股骨、第 2腰椎用于骨密度测量 ,测定双侧子宫重量。结果 :与SHAM组相比 ,OVX组股骨骨密度和椎骨骨密度均可见不同程度降低 (P <0 .0 5和P >0 .0 5 ) ,尼尔雌醇与异黄酮 12 0mg·kg- 1能明显升高去卵巢大鼠的股骨和椎骨骨密度 (P <0 .0 5 )。OVX组的血清碱性磷酸酶水平高于SHAM组 (P <0 .0 5 ) ,异黄酮6 0mg·kg- 1可降低去卵巢大鼠的血清碱性磷酸酶水平 (P <0 .0 5 )。OVX组的血清雌二醇水平与子宫系数明显低于SHAM组 (P <0 .0 1) ,异黄酮的不同剂量组与OVX E组的血清雌二醇水平、子宫系数都明显高于OV     

利维爱和尼尔雌醇对去卵巢大鼠骨质疏松症的实验研究

目的:比较利维爱和尼尔雌醇对去卵巢大鼠骨质疏松的作用并探讨其作用机制。方法:建立去卵巢大鼠骨质疏松模型,40只雌性大鼠随机分成4组:对照组、去卵巢组、尼尔雌醇组和利维爱组。于去卵巢术后1周分别予以利维爱和尼尔雌醇灌胃,10周后观察各组大鼠体重、骨密度及骨形态学的改变,并通过RIA法检测各组大鼠骨组织微环境中细胞因子IL-6和TNF-α的含量。结果:去卵巢组较对照组体重明显增加(P<0.01),骨密度显著下降(P<0.01),骨组织中IL-6、TNF-α含量均显著增高(P<0.01)。尼尔雌醇组体重明显低于去卵巢组(P<0.01)。两组骨密度均显著高于去卵巢组(P<0.01)。骨组织中IL-6、TNF-α含量均显著低于去卵巢组(P<0.01)。但尼尔雌醇组骨密度仍显著低于对照组(P<0.05)。结论:尼尔雌醇较利维爱能更好地抑制去卵巢大鼠的体重增加,二者均能有效预防去卵巢所致大鼠的骨质疏松,其作用机制可能是二药均能有效地抑制去卵巢大鼠骨组织微环境中细胞因子IL-6和TNF-α的含量而减少骨丢失。     

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。     

A combination of subtherapeutic doses of chemically modified doxycycline (CMT-8) and a bisphosphonate (clodronate) inhibits bone loss in the ovariectomized rat: a dynamic histomorphometric and gene expression study

Recent studies have demonstrated that tetracyclines can reduce bone loss in the ovariectomized (OVX) rat model of osteoporosis. In the current study, a non-antimicrobial, chemically modified doxycycline (CMT-8), alone or in combination with a bisphosphonate (Clodronate), was evaluated in this model. Forty-two, 6month old, female rats were randomly assigned to the following groups, (6/ group): a) sham/vehicle, b) OVX/vehicle; c) OVX/1 mg/day CMT-8; d) OVX/2 mg/day CMT-8, e) OVX/1 mg/week Clodronate; and f) OVX/1 mg/day CMT-8 + 1 mg/week Clodronate, CMT-8 was administered by oral gavage, Clodronate injected S/C. Following sham surgery or OVX, the rats were treated for 90 days with CMT-8 or vehicle alone, injected at three different times with fluorochrome labels, the rats were sacrificed, and the tibiae excised for analysis by dynamic bone histomorphometry. Femurs were aseptically removed and analyzed for collagen, collagenase and osteopontin mRNAs by Northern and dot blot analysis. As expected, OVX decreased trabecular bone volume (BV/TV by 73.8% vs. sham p<.01), and also reduced trabecular thickness, numbers, and increased spacing. Bone loss in the OVX animals was partially prevented with either 2 mg/day CMT-8 or 1 mg/wk Clodronate (p<.01), while the 1 mg/day CMT-8 had no effect. Interestingly, the efficacy of the combination therapy of CMT-8 and Clodronate was significantly better than either treatment by itself, maintaining bone mass and structural indices at levels identical to sham values. OVX rats mRNA for collagen, collagenase and osteopontin were elevated indicating high-turnover bone loss. Only COMBO therapy significantly reduced the collagenase and osteopontin mRNA. In summary, CMT-8 mono-therapy (2 mg) alone partially inhibited bone loss in this animal model of osteoporosis. However, 1 mg/day (CMT-8) monotherapy had no effect on bone loss or bone mRNA levels and when combined with Clodronate, interacted to increase efficacy. Thus, a combination of a suboptimal dose of CMT-8 and a bisphosphonate appears to increase the amount of bone by suppressing resorption in a model of osteoporosis.     

Estrogen supplementation modulates effects of the endocrine disrupting pollutant PCB126 in rat bone and uterus: diverging effects in ovariectomized and intact animals

The aims of the present study are to compare effects of estrogen depletion (OVX) and estradiol (E2) supplementation on the tissue effects of exposure to the endocrine disrupting organochlorine 3,3',4,4',5-pentachlorobiphenyl (PCB126). For this purpose two highly estrogen-dependent tissues, bone and uterus, were studied. Forty rats exposed to PCB126 (ip) for 3 months (total dose 384 microg/kg body weight (bw)) were randomized in to OVX/sham operation or E2 supplementation (ip, 23 microg/kg, 3 days weekly) per vehicle (corn oil) groups in a 2 x 2 factorial design. Sham operated rats were treated with vehicle, PCB or PCB plus E2 (sham, sham + PCB and sham + PCB + E2, n=10 per group) whereas ovariectomized were treated with vehicle, PCB or PCB plus E2(OVX, OVX + PCB and OVX + PCB + E2, n=10 per group). As control groups served OVX or sham, and OVX + E2 (n=10 in each group). In OVX rats PCB126 + E2 treatment increased trabecular bone volume (TBV) (P<0.01), whilst the opposite was found in sham-operated rats (P<0.01). In OVX animals exposed to PCB126, E2 supplementation decreased the uterine weight and increased the uterine ERbeta mRNA level, whilst no difference was found between the PCB126 and PCB126 + E2 exposed groups in the sham-operated animals. In conclusion, estrogen modulates PCB126 induced effects on trabecular bone, as well as several uterine parameters. These results further support an important role of estrogen on the toxic effects of PCB126 on bone and uterus.     

哌嗪雌酚酮对去卵巢大鼠骨代谢的作用

目的研究哌嗪雌酚酮(一种新合成雌激素哌嗪类衍生物)对去卵巢大鼠骨代谢及子宫的作用。方法 雌酚酮(E) 0.75 mg·kg^-1·d^-1,哌嗪雌酚酮(P-E) 1和10 mg·kg^-1·d^-1,ig共90 d,骨形态计量学测量。结果去卵巢大鼠子宫萎缩,血清胆固醇升高,骨量减少伴骨高转化的改变。E组与去卵巢组比,子宫重量增加,血清胆固醇降低,骨高转化降低。P-E(1 mg)组与去卵巢组比,子宫重量轻微增加,骨量增加,骨形成和骨吸收均维持在去卵巢组的高水平。P-E(10 mg)组比低剂量组增加更多的骨量,但其作用机理与雌酚酮相同,明显地降低骨转化。结论哌嗪雌酚酮可预防去卵巢大鼠所致的骨丢失。低剂量(1 mg)组对子宫未见明显副作用。     

Alleviation of ovariectomy-induced osteoporosis in rats by <Emphasis Type="Italic">Panax notoginseng</Emphasis> saponins

To examine the effects of Panax notoginseng saponins (PNS), the main active components of Panax notoginseng, on ovariectomy-induced osteoporosis in rats. A total of 72 six-month-old female rats were randomly assigned to sham-operated group and five ovariectomized (OVX) groups: OVX with distilled water (5 ml/kg/day, p.o.), OVX with graded doses of PNS (75, 150, 300 mg/kg/day, p.o.), and OVX with nilestriol (1 mg/kg/week, p.o.). Animals were sacrificed after a 13-week treatment course. Compared with the OVX group, PNS administration prevented OVX-induced decrease in bone mineral density (BMD) of lumbar vertebrae and total femur, and significantly increased bone structural biomechanical properties. Improvements of BMD and biomechanical properties were accompanied by the beneficial changes of PNS on trabecular microarchitecture in the tibial metaphysis. PNS at the highest dose significantly prevent decrease in trabecular bone volume over bone total volume, trabecular number, trabecular thickness, connectivity density, and increase in trabecular separation and structure model index in OVX rats. The bone-modulating effects of PNS may be due to the increased bone formation and decreased bone resorption, as was evidenced by the elevated level of serum alkaline phosphatase and decreased level of urinary deoxypyridinoline. PNS treatment is able to enhance BMD, bone strength, and prevent the deterioration of trabecular microarchitecture without hyperplastic effect on uterus. Therefore, PNS might be a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.     

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats

Objective:

To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol.

Materials and Methods:

Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay.

Results:

At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group.

Conclusions:

Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.KEY WORDS: Lepidium meyenii, maca, ovariectomized rats, serum hormone     

卵巢激素对大鼠结肠组织5-羟色胺受体3的影响

目的　研究不同卵巢激素水平对去卵巢大鼠动物模型结肠组织 5 羟色胺受体 3 (5 HT3 receptors ,5 HT3R )的影响。方法　 2 4只成年♀SD大鼠 ,随机分为 3组 :假手术(Sham)组、去卵巢 (OVX )组、去卵巢加雌激素和孕激素(OVX +E2 +P)组 ,每组 8只。 4wk后观察 1h大鼠排便和玻璃小球排出情况 ;并采用RT PCR方法 ,检测 3组大鼠结肠组织 5 HT3RmRNA的表达。结果　OVX组大鼠较Sham组及OVX +E2 +P组排便量增加 ,玻璃小球排出时间缩短 (P <0 0 1) ;OVX组与Sham组及OVX +E2 +P组比较 ,5 HT3RmRNA的表达明显增加 (P <0 0 1) ;OVX +E2 +P组与Sham组比较 ,5 HT3RmRNA的表达减少 (P <0 0 1)。结论　卵巢激素对胃肠道 5 HT3R的调节方面有重要作用