不同剂量来曲唑联合醋酸甲羟孕酮对大鼠子宫内膜异位症模型作用的研究

目的:探讨不同剂量来曲唑(LE)及醋酸甲羟孕酮(MPA)联合应用对大鼠子宫内膜异位症(EMT)模型的治疗效果及对肝、肾、骨以及生殖系统的影响,为LE临床治疗绝经前EMT提供实验基础。方法:应用自体子宫内膜移植方法建立大鼠EMT模型,将70只建模成功大鼠随机分为7组,每组10只:A~C组为LE 1 mg/(kg·d~(-1))+MPA[分别为8、4、2 mg/(kg·d~(-1))],D~F组为LE 0.5mg/(kg·d~(-1))+MPA[分别为8、4、2 mg/(kg·d~(-1))];G组为0.9%氯化钠液(对照组)。比较治疗前后大鼠EMT异位病灶体积的变化,检测异位病灶中细胞色素P450芳香化酶(P450arom)、Ki-67蛋白的表达及细胞凋亡情况,测定大鼠血清FSH、LH、E_2水平及肝、肾功能,取右侧股骨测量骨密度。结果:(1)除F组外,LE联合MPA各剂量组治疗后的异位病灶体积与G组比较均缩小(P0.05),以A组和B组体积缩小最为显著(P0.01)。(2)与G组相比,A~C组异位内膜中P450arom、Ki-67蛋白表达均低于G组(P0.05或P0.01),而异位内膜细胞凋亡率均高于G组(P0.01),且以A、B两组最为明显(P0.01)。(3)与G组相比,A、B、D组大鼠血清FSH、LH、E_2水平均降低(P0.05或P0.01),而且A组、B组的E_2水平更低。(4)与G组比较,C组大鼠卵巢质量明显增加(P0.01),卵巢呈多囊改变;除F组外各治疗组子宫质量与G组比较均减轻(P0.01),内膜均呈增生抑制或萎缩改变。(5)各剂量组的大鼠骨密度均无明显变化(P0.05)。(6)仅A组治疗后出现肝功能异常,各组肾功能均未出现异常(P0.05)。结论:LE 1 mg/(kg·d~(-1))联合MPA 4 mg/(kg·d~(-1))治疗效果最佳,且对肝肾功能无影响。其作用可能与通过协同降低大鼠血清E_2水平并减少异位内膜局部雌激素的分泌,抑制异位内膜增殖并促进凋亡有关。     

雷洛昔芬对绝经后妇女骨密度、骨代谢生化指标和血脂影响的随机对照研究

目的　确定盐酸雷洛昔芬 (RLX)对中国绝经后妇女骨密度、骨代谢生化指标及血脂的影响。方法　将来自 3所医院的 2 0 4例绝经后妇女 [平均年龄 (6 0± 5 )岁 ,平均体重 (6 3± 9)kg]随机分组 ,进行双盲安慰剂对照的临床研究 ,受试者每天接受RLX 6 0mg(n =10 2 ,RLX组 )或安慰剂 (n =10 2 ,安慰剂组 )治疗 12个月 ,并于服药前及服药 12个月后各进行一次骨密度、骨代谢生化指标及血脂的测定。结果　与安慰剂相比 ,RLX使腰椎和髋部骨密度显著升高 ,RLX组腰椎的骨密度增加2 30 % ,而安慰剂组降低 0 0 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1) ;RLX组髋部骨密度增加2 4 6 % ,安慰剂组增加 1 0 7% ,两组比较 ,差异有显著性 (P <0 0 5 )。RLX组骨代谢生化指标血清骨钙素和血清C端交联肽分别降低 2 7 6 %和 2 4 0 % ,而安慰剂组则分别降低 10 6 %和升高 15 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。RLX组总胆固醇和低密度脂蛋白胆固醇分别降低 6 4 %和34 6 % ,而安慰剂组则分别升高 1 4 %和降低 19 1% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。两组间高密度脂蛋白胆固醇和甘油三酯水平未见差异。仅有 5例因不良事件而提前退出研究 (RLX组 3例 ,安慰剂组 2例 )。结论　RLX能增加绝经后中国妇女     

青春期大鼠受己烯雌酚持续作用对成年后睾丸结构与功能的影响

目的：探讨青春期大鼠受己烯雌酚(DES)持继作用后的睾丸损伤,损伤后在成年期的睾丸结构及生精功能能否恢复。方法：青春期雄性SD大鼠48只,随机均分成：A_1、B_1、C_1和D_1组；A_2、B_2、C_2和D_2组。分别隔日腹腔注射含DES0μg·kg~(-1)·d~(-1)(A_1,A_2,为对照组)、2μg·kg~(-1)·d~(-1)(B_1,B_2)、10μg·kg~(-1)·d~(-1)(C_1,C_2)和50μg·kg~(-1)·d~(-1)(D_1,D_2)的玉米油0.3 ml,28 d后处死A_1-D_1组动物采集标本。A_2-D_2组则继续正常饲养60 d(恢复期),然后处死动物取材。检测大鼠体重(BW)、睾丸重量(TW)、附睾重量(EW)、睾丸每日精子生成量(DSP)以及附睾尾精子数(ESC)等5项参数的变化,应用光镜观察睾丸生精上皮的组织学变化。结果：B_1组的TW、DSP和ESC显著低于A_1组(P＜0．01),C_1组和 D_1组的5项参数均显著低于A_1组(P＜0．05)。与A_2组相比较,B_2组的5项参数均没有显著性差异(P＞0．05),C_2组DSP和ESC显著减少(P＜0．05),D_2组则TW、EW、DSP和ESC显著降低(P＜0．01)。DES染毒各组的睾丸曲细精管出现了不同程度的萎缩,且随剂量增加病理改变程度加重。恢复期后,睾丸曲细精管组织结构B_2组显示正常,C_2组有明显恢复,D_2组未得到恢复。结论：青春期大鼠受DES持续作用可导致睾丸生精上皮损伤,生精能力下降。损伤较轻组在成年后,睾丸组织结构和生精功能得到不同程度的恢复,但损伤程度重者未见恢复。     

莉芙敏对去卵巢大鼠下丘脑视前区5-HT1AR和5-HT2AR表达的影响

目的:观察去卵巢大鼠应用黑升麻异丙醇提取物--莉芙敏(ICR)治疗1-4周后,免疫组化方法检测5-羟色胺1A受体(5-HT1AR)和5-HT2AR在大鼠下丘脑视前区表达的变化情况,为莉芙敏缓解围绝经期潮热症状的机制研究提供形态学依据.方法:雌性大鼠分为假手术组(Sham组)、去卵巢组(OVX组)、OVX后戊酸雌二醇治疗(OVX+E2)组和OVX后ICR治疗(OVX+ICR)组,每组40只.所有大鼠术后恢复2周后,再用相应的药物分别治疗1,2,3,4周,麻醉,心脏灌注,取脑,制作冰冻切片.免疫组化法观察各组大鼠下丘脑视前区5-HT1AR和5-HT2AR的表达.结果:①OVX组1-4周时大鼠下丘脑视前区5-HT1AR阳性细胞数量和吸光度均较同期Sham组增加;ICR和戊酸E2治疗1-4周后,OVX+E2组和OVX+ICR组大鼠下丘脑视前区室周带表达5-HT1AR的阳性细胞数量和吸光度均较同期OVX组减少.②下丘脑视前区中间带和外侧区5-HT2AR阳性细胞数量和吸光度的变化:OVX组大鼠,1-4周均较同期Sham组增加;ICR和戊酸E2治疗1周和2周后,OVX+E组和OVX+ICR组较同期OVX组增加;治疗3周和4周后,OVX+E2组和OVX+ICR组均较同期OVX组减少.结论:5-HT1AR和5-HT2AR在去卵巢大鼠下丘脑视前区的表达量均增加;ICR和戊酸E2治疗后,5-HT1AR在大鼠下丘脑视前区的表达量减少,而5-HT2AR在下丘脑视前区的表达先增多后减少.ICR可能通过调节下丘脑视前区体温调节中枢的5-HT1AR和5-HT2AR的表达,以缓解围绝经期的潮热症状.     

卵巢切除和雌激素补充治疗对大鼠膀胱功能及结构的影响

目的通过对不同雌激素水平大鼠进行膀胱功能、组织形态和超微结构的比较,探讨雌激素对膀胱功能的影响及其作用机制。方法30只雌性成年SD大鼠均分为3组:OVX+E组(切除双侧卵巢后补充戊酸雌二醇0·8mg·kg-1·d-1,溶于0·5%羧甲基纤维素钠,每日灌胃1次)、OVX组(切除双侧卵巢)、正常对照组(未切除卵巢),后两组大鼠每日给予0·5%羧甲基纤维素钠灌胃1次。3组大鼠用药12周后行膀胱压力容积测定,并用切除膀胱的石蜡切片分析胶原纤维和平滑肌的面密度及两者比值,透射电镜下观察逼尿肌的超微结构。结果(1)OVX组膀胱最大容量(0·32±0·20)ml、顺应性(0·012±0·006)ml/cmH2O(1cmH2O=0·098kPa)和最大收缩力(1·4±0·4)cmH2O,相对于正常对照组[分别为(1·11±0·09)ml、(0·026±0·003)ml/cmH2O和(4·4±0·3)cmH2O]明显减少,差异均有统计学意义(P<0·05)。OVX+E组膀胱最大容量为(0·83±0·10)ml,相对于正常对照组减少(P<0·05),而膀胱顺应性(0·029±0·003)ml/cmH2O、最大收缩力(4·8±1·4)cmH2O与正常对照组比较,差异无统计学意义(P>0·05)。(2)胶原纤维面密度、胶原纤维面密度/平滑肌面密度比值,OVX组分别为0·218±0·041和0·54±0·08,相对于正常对照组(0·160±0·039、0·32±0·09)明显增加,差异有统计学意义(P<0·05);而OVX+E组(0·178±0·027、0·38±0·06)与正常对照组比较,差异无统计学意义(P>0·05)。(3)电镜观察OVX组逼尿肌超微结构出现退行性改变,其他两组无类似变化。结论大鼠切除双侧卵巢后膀胱功能明显降低,补充雌激素有利于改善膀胱功能,这一作用可能是通过抑制胶原增生,保护细胞器来实现的。     

吗啡对雌性大鼠性腺轴和骨组织的影响

目的:研究吗啡对雌性大鼠性腺轴和骨组织的影响。方法:选取3月龄雌性大鼠45只,随机分为吗啡组30只和对照组15只。吗啡组采用剂量递增法皮下注射盐酸吗啡12周,对照组注射同等体积的生理盐水12周。放射免疫法测定血清FSH、LH、E2、P;免疫组织化学检测下丘脑、垂体、卵巢雌激素受体(ER)和β-内啡肽(β-EP)的表达;原位杂交方法测定下丘脑、垂体和卵巢的μ-阿片受体mRNA的表达;双能X线骨密度测量仪测量不同部位的骨密度值;测量骨代谢生化指标;对骨组织切片进行形态计量分析;并用RT-PCR方法检测骨组织中雌激素受体(ER)mRNA的变化。结果:(1)吗啡组FSH、LH、E2、P基础分泌较对照组降低(P<0·01,P<0·05,P<0·01,P<0·05);(2)吗啡组大鼠性腺轴各组织中ER平均光密度值均显著降低(P均<0·01);(3)吗啡组大鼠下丘脑、垂体β-内啡肽的含量下降,而μ-阿片受体mRNA表达增强;(4)吗啡组大鼠股骨远侧干骺端和胫骨近侧干骺端骨密度以及骨组织中ERmRNA表达均较对照组显著下降(P<0·05),组织切片观察显示,吗啡组大鼠骨小梁纤细、断裂、形态结构完整性差,骨髓腔大小不一,对照组大鼠骨小梁粗壮、饱满、形态结构完整,骨髓腔相对较小,计量分析显示,吗啡组骨小梁面积明显低于对照组(P<0·05);骨代谢生化指标结果显示,吗啡组大鼠血清钙和尿钙以及TRAP、HOP较对照组增加显著(P<0·05)。结论:长期使用吗啡对下丘脑-垂体-卵巢轴及骨组织会有不同程度的损伤。     

绝经后妇女雌激素受体基因多态性与骨和脂代谢的相关性研究

目的 :研究绝经后妇女雌激素受体 (ER)基因PvuII、XbaI限制性片段长度多态性与骨和脂代谢的关系。方法 :随机选取 5 7名已排除影响骨代谢、脂代谢疾病的绝经后妇女 ,采空腹血和晨尿 ,用PCR RFLP法对ER基因多态性进行分析 ;DEXA测定腰椎正侧位及股骨骨密度 ,同时检测血骨钙素、尿I型胶原N末端肽和血脂指标。结果 :xx组股骨干(SHAFT)骨密度明显低于Xx组 (P <0 .0 5 )。XbaI限制性片段长度多态性与股骨SHAFT骨密度相关 (r =0 .36 7,P =0 .0 39) ;XX组骨钙素高于xx(P =0 .0 4 1)和Xx(P =0 .0 11)组。apoA1含量和A1/B比值在xx、Xx、XX三组递增 ,各组间差异有显著性 (P <0 .0 5 )。Lp(a)与股骨骨密度 (除SHAFT外 )呈负相关。结论 :ER基因XbaI RFLP是影响绝经后妇女骨和脂代谢的重要因素 ;X基因型可维持股骨骨量 ,xx基因型与低apoA1含量和A1/B比值相关 ,Lp(a)也影响股骨骨密度     

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。     

莉芙敏对去卵巢大鼠下丘脑视前区5-HT1AR和5-HT2AR表达的影响

目的:观察去卵巢大鼠应用黑升麻异丙醇提取物--莉芙敏(ICR)治疗1-4周后,免疫组化方法检测5-羟色胺1A受体(5-HT1AR)和5-HT2AR在大鼠下丘脑视前区表达的变化情况,为莉芙敏缓解围绝经期潮热症状的机制研究提供形态学依据.方法:雌性大鼠分为假手术组(Sham组)、去卵巢组(OVX组)、OVX后戊酸雌二醇治疗...     

橄榄油治疗SD大鼠去势后骨质疏松的效果研究

目的:探讨橄榄油对SD大鼠去势后骨质疏松骨代谢血清生化及骨组织学指标的改善作用。方法:将36只12~14个月龄清洁型成年SD大鼠进行随机平均分为3组:假手术组(Sham组)、去卵巢组(OVX组)、去卵巢+橄榄油组(OVX+橄榄油组)。以1 ml/100 g体重橄榄油1次/天灌胃,连续12周。各组12周后分别左心室取血,检测血清钙、磷、碱性磷酸酶(ALP)、丙二醛(MDA)和硝酸盐含量;取出大鼠左侧股骨测胫骨皮质骨厚度(CBT)、骨小梁厚度(TBT)和破骨细胞数量(OCL)。结果:OVX+橄榄油组与OVX组比较,血清中磷水平差异无统计学意义(P0.05),血清中ALP、MDA、硝酸盐水平降低(155.84±0.18 U/L vs 202.62±0.16 U/L,P0.05;1.76±0.04μmol/L vs 2.58±0.06μmol/L,P0.05;9.16±0.38μmol/L vs 21.23±0.36μmol/L,P0.05)。3组血清中钙水平两两比较,差异均无统计学意义(P0.05)。OVX+橄榄油组与OVX组比较,CBT和TBT增高(243.35±0.17μm vs 203.82±0.14μm,P0.05;88.29±0.18μm vs 53.57±0.16μm,P0.05);OCL显著减少(7.64±0.37/10 HPF vs 15.08±0.37/10 HPF,P0.05)。结论:橄榄油能改善去势大鼠骨质疏松ALP、MDA、硝酸盐骨代谢血清生化指标及骨组织学指标,在治疗绝经后骨质疏松症方面可能有较好的前景。     

Effects of strontium ranelate,raloxifene and misoprostol on bone mineral density in ovariectomized rats

Objectives

To investigate the effects of strontium ranelate, raloxifene and misoprostol on bone mineral density (BMD) in ovariectomized rats to contribute to the individualization of the treatment of postmenopausal osteoporosis.

Study design

Sixty sexually mature female Sprague–Dawley rats weighing 250 g were used. The 60 rats were divided into six groups of 10 rats each: SR, MISO, RAL, SHAM, DW and OVX. All except the SHAM rats were subjected to bilateral ovariectomy. Three days after surgery, rats were administered strontium ranelate (Protelos^®, 2 g, Servier, Istanbul), 1800 mg/kg/day; misoprostol (Cytotec^®, 200 mcg, Ali Raif, Istanbul), 200 mcg/kg/day; raloxifene (Evista^®, 60 mg, Lily and Company, Istanbul), 3 mg/kg/day and 1 cc of distilled water by gavage for 8 weeks. Bone mineral density measurements were then performed.

Results

The strontium ranelate (SR) group had significantly higher vertebral BMD than all other groups. Femoral density in the SR group was also significantly higher than in other groups and there was no difference between femoral density in the strontium ranelate and sham groups.

Conclusions

Strontium ranelate, raloxifene and misoprostol can prevent bone loss in the vertebrae, whereas strontium ranelate can also prevent bone loss in the femur of ovariectomized rats. Strontium ranelate increases greater than raloxifene and misoprostol BMD in the vertebrae.

Condensation

Strontium ranelate may increase both vertebral and femur BMD in ovariectomized rats while raloxifene and misoprostol may only increase lumbar spine BMD.     

雌激素、三苯氧胺与氟化物配伍预防去势大鼠骨丢失的研究

目的　比较三苯氧胺与雌激素对骨代谢的影响 ,及两者与氟化物配伍后是否产生协同效果。方法　将 142只 6月龄雌性SD大鼠行去势手术或假手术后随机分为 7组 (每组 19～ 2 1只 ) :(1)假手术组 ;(2 )去势组 ;(3)雌激素组 ;(4 )氟化物组 ;(5 )雌激素 +氟化物组 ;(6 )三苯氧胺组 ;(7)三苯氧胺 +氟化物组。治疗 12个月 ,行骨密度、腰椎骨组织形态计量学参数 (不脱钙骨切片 )、右股骨中段三点弯曲试验观察 ,并行子宫病理及血脂检查。结果　 (1)术后 12个月时 ,全身骨密度去势组为2 79mg/cm2 、治疗组为 2 86～ 2 98mg/cm2 ,腰椎骨密度分别为 2 32mg/cm2 、2 5 1～ 2 6 6mg/cm2 (P均<0 0 5 ) ;股骨中段骨密度 ,雌激素组 2 16mg/cm2 ,明显高于三苯氧胺组 195mg/cm2 (P <0 0 5 ) ;配伍治疗组与单药治疗组无明显差异 (P >0 0 5 )。 (2 )术后 4个月 ,两个配伍治疗组最大载荷 (均为 145牛顿 )与去势组 [(118± 2 4)牛顿 ]有显著差异 (P <0 0 5 ) ;术后 12个月各治疗组最大载荷为 132～ 15 5牛顿 ,均明显高于去势组 (10 8± 13)牛顿 (P <0 0 5 ) ,雌激素组最大载荷、弹性载荷均明显高于三苯氧胺组 (P <0 0 5 )。 (3)各组骨组织形态计量学检查未发现骨矿化不良现象。结论　雌激素在维持骨量、骨强度方面优于三苯     

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。     

雷洛昔芬对去卵巢大鼠骨密度及血E2、IL-6水平影响的研究

目的观察雷洛昔芬对去势大鼠骨密度、血清E2、IL-6及子宫内膜的影响，探讨雷洛昔芬抗骨质疏松的作用机制。方法48只3个月龄雌性SD大鼠，随机分为SHAM组（假手术），0VX组（单纯去势），0VX＋E2组（去势＋雌激素），0VX＋R组（去势＋雷洛昔芬），每组12只。3个月后处死采集血，用放射免疫分析法检测并比较各组E2及IL-6的表达，取子宫内膜用HE染色法观察各组子宫内膜的形态变化并对子宫内膜腺体数目进行统计学分析。结果雷洛昔芬组大鼠骨密度显著高于去卵巢组（P＜0．05），血清IL-6浓度值显著降低，雌激素浓度的改变差异无统计学意义（与去卵巢组比较P＞0．05），对子宫内膜无明显影响（P＞0．05）。结论雷洛昔芬治疗骨质疏松的作用与血清中IL-6水平降低相关，与雌激素无显著相关，对子宫内膜无显著影响。     

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.     

淫羊藿对去卵巢大鼠骨组织白细胞介素6 mRNA表达的影响

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The effect of prolactin itself and in combination with estrogen on bone mineral density in female rats

Abstract

Estrogen deficiency induced by hyperprolactinemia can reduce bone mineral density. Hyperprolactinemia through other mechanisms other than estrogen deficiency, with direct effect on the bone might cause bone loss in women. The present study evaluated the effect of prolactin itself and in combination with estrogen on bone mineral density of female rats. This study was performed on 50 adult female rats divided into five groups; included (a) Sham, (b) Ovariectomized rats; and (c–e) included ovariectomized rats were given prolactin alone, prolactin?+?estradiol and estradiol, respectively. Bone mineral density (BMD) and vitamin D metabolism parameters were checked in all groups before and after the study. There was no significant difference in baseline values of these parameters. Estradiol could increase 1,25(OH)2D3 and PTH levels and decrease serum ALP level. In addition, Prolactin could increase serum 1,25(OH)2D3 and ALP levels and decrease tibia BMD significantly without any change in PTH level. Combination of estradiol and prolactin could increase serum 1,25(OH)2D3 and PTH and tibia BMD compared with OVX group. Combination of estradiol and prolactin could significantly increase tibia BMD, in ovariectomized rats. We hypothesized that this combination could improve bone loss secondary to hyperprolactinemia by elevated PTH.     

戊酸雌二醇对去卵巢大鼠骨质疏松的治疗作用

目的评价国产戊酸雌二醇对去卵巢大鼠骨质疏松的治疗作用.方法雌性健康未交配Wistar大鼠42只,于6月龄时分别行去卵巢和假手术,分组并行如下处理(1)治疗前对照组(8只)于去卵巢后6周处死;(2)治疗末对照组(8只);(3)假手术组(8只);(4)去卵巢17β雌二醇治疗(O+E)组(9只)去卵巢后6周予17β雌二醇20μg@kg-1@d-1皮下注射;(5)去卵巢戊酸雌二醇治疗(O+EV)组(9只)去卵巢后6周予戊酸雌二醇800μg/kg@d-1经胃肠道给药,后4组于去卵巢后14周处死,留取右侧胫骨、股骨及血标本,处死前收集24h尿标本,分别进行骨组织计量学、外周骨定量CT检查、股骨远端凹入实验,以及骨吸收指标脱氧吡啶啉等测定.结果去卵巢后,骨矿盐含量(骨量)减少,骨小梁结构稀疏,骨吸收和骨形成指标均增加.股骨远端松质骨骨量和骨矿盐密度(骨密度)显著降低,松质骨最大载荷和刚度均明显下降.与治疗末对照组相比,O+E和O+EV组骨吸收指标尿脱氧吡啶啉分别下降54.6%和77.4%(P均＜0.01),骨转换受抑制,胫骨近端次级骨小梁的体积比率分别增加122.3%和119.7%[(12.9±0.8)%和(12.8±0.9)%与(5.8±1.3)%比较,P＜0.01],骨小梁的结构得到改善.O+E和O+EV组股骨远端松质骨骨矿盐密度较治疗末对照组分别增加99.5%和128.4%,分别为(258.9±16.9)和(269.2土24.3)mg/cm2比(117.8±30.4)mg/cm3(P＜0.01).O+E组的股骨远端松质骨最大载荷和刚度均较治疗末对照组有显著增加(P均＜0.05),以上各指标在0+E和0+EV组之间差异无显著性.结论戊酸雌二醇能有效地抑制去卵巢大鼠过高的骨转换,使小梁骨骨量增加,结构改善,松质骨的力学特征得到改善.     

Effects of resveratrol, raloxifene, tibolone and conjugated equine estrogen on vaginal squamous cell maturation of ovariectomized rats

OBJECTIVE: The effects of estrogen replacement therapy, selective estrogen receptor modulators, or tibolone on vaginal squamous cell maturation in postmenopausal women are not well established. Resveratrol (3,5,4'-trans-trihydroxystilbene) has been shown to bind the estrogen receptor in rat uteri. The aim of this study was to cytologically evaluate vaginal smears from ovariectomized rats treated with resveratrol, raloxifene, tibolone and conjugated equine estrogen, and to compare each drug with regard to vaginal epithelial maturation. MATERIAL AND METHODS: Forty-two bilaterally ovariectomized Wistar albino rats were equally randomized into 6 groups: (1) control sham-operated rats; (2) ovariectomized rats administered 0.1% ethanol; (3) ovariectomized rats administered resveratrol at a dose of 5 mg/kg/day p.o.; (4) ovariectomized rats administered conjugated equine estrogen (CEE) at a dose of 0.1 mg/kg/day p.o.; (5) ovariectomized rats administered tibolone at a dose of 0.25 mg/kg/day p.o., and (6) ovariectomized rats administered raloxifen at a dose of 1 mg/kg/day p.o. Administration of drugs started 5 days after bilateral ovariectomy and continued for 35 days. After 35 days of treatment a vaginal smear was obtained from each rat. Smears were stained with the usual Papanicolaou method, and observed with a light microscope by an experienced cytopathologist. Cytological grading was made according to the extent of parabasal, intermediate, superficial and anuclear squamous cells. RESULTS: Ovariectomized rats had lower scores for superficial and anuclear cells when compared to sham-operated rats (p < 0.05). The CEE group had higher scores for superficial and anuclear cells than those of the ovariectomized, raloxifene and tibolone groups (p < 0.05). The resveratrol-treated rats had higher scores for superficial cells but lower scores for parabasal cells than ovariectomized rats (p < 0.05). The raloxifene and tibolone groups had the same scores for intermediate, superficial and anuclear cells but lower scores for parabasal cells compared to ovariectomized rats. CONCLUSION: The results of our study suggest that resveratrol offsets the reduction in vaginal stratification generally observed after oophorectomy.