TGF-β_1在PCOS卵巢间质纤维化形成中的作用

目的:探讨TGF-β1在PCOS大鼠卵巢间质纤维化、包膜硬化形成中的作用。方法:利用脱氢表雄酮(DHEA)皮下注射的方法建立PCOS病理模型大鼠20只,用微粒子酶免分析法测定血清性激素E2、T、LH、FSH、LH/FSH、空腹胰岛素(FINS)水平,及光镜下观察PCOS大鼠卵巢的病理结构,透射电镜观察细胞超微结构来验证模型。采用免疫组化法检测PCOS组(n=20)卵巢细胞因子TGF-β1的表达,并与20只正常大鼠相比照。结果:TGF-β1在PCOS组各阶段卵泡卵母细胞、颗粒细胞的表达强度与对照组相比,差异无统计学意义(P>0.05)。而在窦状卵泡膜细胞和卵巢间质细胞中的表达,PCOS组显著高于对照组(P<0.01,P<0.05)。结论:多囊卵巢中TGF-β1表达异常,可能是导致多囊卵巢间质纤维化、包膜增厚的原因之一,TGF-β1也参与PCOS卵泡发育、闭锁的调控。     

碱性成纤维细胞生长因子对新生大鼠缺血脑组织转化生长因子β1及其受体mRNA表达的影响

目的 研究碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)对3日龄新生大鼠脑缺血后星形胶质细胞数目以及转化生长因子-β1(transforming growth factor-β1,TGF-β1)及其受体--Smad2mRNA表达的影响,探讨bFGF对未成熟脑缺血性损伤的保护作用机制. 方法 结扎3日龄新生SD大鼠双侧颈总动脉制备脑缺血模型,随机分为对照组(33只)、治疗组(33只).另取3日龄新生SD大鼠33只为假手术组.免疫荧光染色方法检测三组大鼠术后4 d、7 d和14 d脑室下区胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)阳性细胞数目;实时荧光定量PCR(real-time PCR)技术检测三组大鼠术后4 d、7 d和14 d脑室下区TGF-β1及Srnad2 mRNA表达变化. 结果 (1)假手术组GFAP阳性细胞术后7 d达高峰[(325.4±52.5)个/视野],对照组、治疗组GFAP阳性细胞数术后14 d达高峰[分别为(533.5±75.7)、(727.2±104.5)个/视野)],三组同时点比较差异有统计学意义(P＜0.01).(2)对照组TGF-β1和Smad2 mRNA表达在术后7 d达高峰(分别为7.67±1.22和6.22±1.92),治疗组TGF-β1和Smad2 mRNA表达在术后14 d达高峰(分别为8.65±1.02和7.67±1.41),三组同时点比较差异有统计学意义(P＜0.01). 结论 未成熟脑缺血后,外源性bFGF可通过诱导TGF-β1的表达,引起星形胶质细胞反应性增生,而发挥其神经营养作用.     

IFN-γ对溴隐亭诱导的流产大鼠下丘脑-垂体-卵巢中TGF-β1表达的影响

目的:探讨γ-干扰素(IFN-γ)对流产大鼠下丘脑-垂体-卵巢中转化生长因子β1(TGF-β1)表达的影响。方法:将40只孕1 d SD大鼠随机分为4组,分别为正常组(A组)、流产模型组(B组)、流产模型+IFN-γ组(C组)和流产模型+IFN-γ抗体组(D组),每组10只。B～D组于孕6～8 d每日皮下注射溴隐亭0.3 mg/kg,建立流产模型;C组于孕9～11 d每日肌注IFN-γ(100 IU/kg);D组于于孕9～11 d每日肌注IFN-γ抗体(100μg/kg)。妊娠12 d灌注多聚甲醛固定后取材,采用免疫组织化学SP法对每组下丘脑、垂体和卵巢中TGF-β1的表达进行检测。结果:B、C组下丘脑、垂体和卵巢中TGF-β1阳性细胞数和OD值均较A组低,D组下丘脑和垂体中TGF-β1阳性细胞数和OD值较A组低;C组下丘脑、垂体和卵巢中TGF-β1阳性细胞数、下丘脑和卵巢中OD值均低于B组;D组下丘脑、垂体和卵巢中TGF-β1阳性细胞数和OD值均较B、C组低。结论:IFN-γ对流产大鼠下丘脑-垂体-卵巢中TGF-β1的表达具有下调作用。     

胚胎停育绒毛组织中TGF-β1、MMP-9及TIMP-1的表达及意义

目的:探讨TGF-β1、MMP-9及TIMP-1 mRNA的表达在胚胎停育发病机制中的作用。方法:用半定量逆转录聚合酶链反应(RT-PCR)技术检测正常人工流产(20例)和胚胎停育(25例)患者绒毛组织中TGF-β1、MMP-9与TIMP-1 mRNA的表达量。结果:(1)与对照组相比,实验组绒毛中TGF-β1 mRNA和TIMP-1 mRNA的表达量降低(P<0.05),而MMP-9 mRNA表达量升高(P<0.05);(2)绒毛组织中TGF-β1 mRNA与MMP-9 mRNA的表达呈负相关(r=-0.82,P<0.05)。结论:胚胎停育患者绒毛组织TGF-β1、MMP-9以及TIMP-1 mRNA表达有明显改变;TGF-β1表达的降低可能上调MMP-9表达,通过破坏MMPs/TIMPs动态平衡,最终导致胚胎停育发生。     

Foxp3以及TGF-β1对胚胎反复种植失败的影响

目的:研究黄体中期和取卵后第6天外周血Foxp3、TGF-β1 mRNA的表达情况,探究二者表达对胚胎反复种植失败的影响。方法:以反复种植失败16例为实验组,以同期接受IVF-ET第1周期并妊娠的25例为对照组。分别抽取黄体中期(LH)和取卵后(OPU)第6天的空腹静脉血各2ml(要求P≥5ng/ml),采用RT-PCR法检测Foxp3和TGF-β1 mRNA水平。结果:反复移植失败组外周血d(LH+6)、d(OPU+6)Foxp3 mRNA表达和对照组相比,差异有统计学意义(分别为0.561±0.029 vs 0.718±0.0291,0.594±0.034 vs 0.727±0.030,P均<0.05)。反复种植失败组外周血d(LH+6)、d(OPU+6)TGF-β1 mRNA水平与对照组相比,差异均有统计学意义(分别为0.638±0.056 vs 0.849±0.056、0.731±0.035 vs 0.837±0.052,P均<0.05)。结论:反复种植失败患者外周血Foxp3及免疫抑制因子TGF-β1的表达降低,可能是反复种植失败免疫性不孕的原因。     

TGF-β1在早孕妇女外周血和蜕膜组织中诱导生成T调节性(Treg)细胞

目的:研究TGF-β1是否能在人母-胎界面诱导生成T调节性(Treg)细胞。方法:早孕妇女外周血和蜕膜CD4+CD25-T细胞中加入不同浓度的TGF-β1(0 ng/ml、2 ng/ml、5 ng/ml、10 ng/ml)分别于培养后第2日、第4日和第6日用流式细胞仪检测培养Foxp3的表达情况,随后将诱导生成的CD4+Foxp3+T细胞与CD8+T细胞混合培养,观察后者凋亡因子CD95配体(CD95L)的表达情况。结果:体外培养中,TGF-β1可诱导早孕妇女的外周血和蜕膜CD4+CD25-T细胞生成诱导性Treg细胞,随着培养时间增加而增强诱导效应,且在TGF-β1浓度为5 ng/ml时诱导功能最强;诱导生成的CD4+Foxp3+T细胞具有促进效应细胞CD8+T细胞凋亡的功能。结论:体外培养中,TGF-β1能将人外周血和蜕膜诱导生成Treg细胞,且具有免疫抑制功能,有良好的免疫治疗前景。     

转化生长因子β1β3及其受体βRⅠβRⅡmRNA在子宫肌瘤组织中的表达

目的　探讨转化生长因子 β1、β3 (TGF β1、β3 )及其受体 βRⅠ、βRⅡmRNA与子宫肌瘤发生发展的关系。方法　 2 0 0 0年 12月至 2 0 0 1年 11月采用免疫组化及原位杂交染色方法 ,对 30例子宫肌瘤及正常子宫肌组织标本检测TGF β1、β3 及其受体 βRⅠ、βRⅡmRNA的表达。 结果　 (1)子宫肌瘤组织中TGF β1、β3 蛋白表达强于邻近正常肌层 (P <0 0 1) ,且黄体期较卵泡期增高 (P <0 0 1)。TGF βRⅠ水平较邻近正常肌层亦增高 (P <0 0 1) ,TGF βRⅡ则下降 (P <0 0 5 )。 (2 )原位杂交TGF β1、β3 mRNA杂交信号的检测结果与免疫组化检测结果一致。结论　TGF β1、β3 与子宫肌瘤的发生发展密切相关 ,TGF βRⅡ降表达或表达异常可能是TGF βs促进子宫肌瘤发生发展的始动环节     

早期自然流产患者TNF-α及TGF-β1的异常表达

目的:探讨自然流产患者外周血单个核细胞和胎盘组织肿瘤坏死因子-α(TNF-α)以及转化生长因子-β(TGF-β1)的异常表达。方法:采用RT-PCR技术,检测30例早期自然流产患者(自1然流产组)、25例正常妊娠妇女(正常妊娠组)、25例正常未妊娠妇女(未孕对照组)外周血单个核细胞内TNF-αmRNA和TGF-β1mRNA表达水平;采用免疫组织化学技术检测绒毛和蜕膜组织内TNF-α及TGF-β1表达强度。结果:三组研究对象外周血单个核细胞表达TNF-αmRNA相对含量分别为21.1±9.4%、68.6±14.1%、97.0±11.6%,组间比较有显著性差异(P<0.05);TGF-β1mRNA相对含量分别为21.5±9.4%、95.7±12.9%、87.0±13.8%,组间比较也均有显著性差异(P<0.05)。自然流产组细胞滋养层细胞及合体滋养层细胞表达TNF-a均显著强于人工流产组(P<0.01);自然流产组合体滋养层细胞表达TGF-β1显著低于人工流产组(P<0.01)。结论:①早期自然流产患者外周血单个核细胞TNF-αmRNA表达水平显著下降,而细胞滋养层细胞及合体滋养层细胞表达TNF-α均显著强于人工流产组,提示TNF-α可能在母胎界面局部发挥作用并导致流产。②正常早期妊娠妇女外周血单个核细胞TGF-β1mRNA表达水平较正常未妊娠妇女显著升高,提示TGF-β1对妊娠维护起重要作用。早期自然流产患者外周血单个?     

溴隐亭致流产大鼠TGF-β1、IL-2、IL-4的表达变化及意义

目的:研究转化生长因子-B1(TG9F-β1)、白细胞介素-2(IL-2)、白细胞介素-4(IL-4)在溴隐亭致流产大鼠黄体及血清的表达水平,探讨流产的发生机制.方法:将孕雌性wistar大鼠随机分为3组,正常孕组、注射溴隐亭组、注射溴隐亭+γ-干扰素(IFN-γ)抗体组,3组均于孕12天时,腹主动脉采血后心内灌注固定,酶联免疫吸附试验(ELISA)测定各组血清TGF-β1、IL-2、IL-4水平,免疫组化SP法检测TGF-β1、IL-2、IL-4在各组大鼠卵巢黄体的表达并进行图像分析,分别对上述结果进行单因素方差分析及t检验.结果:血清与卵巢黄体阳性细胞OD值的变化趋势基本一致,注射溴隐亭组,IL-2水平较正常孕组升高(P<0.05)、TGF-β1、IL-4水平较正常孕组降低(P<0.05);注射溴隐亭+IFN-γ抗体组,血清IL-2水平较注射溴隐亭组有所降低(P<0.05),但仍高于正常孕组(P<0.05),而TGF-β1、IL-4水平有所升高(P<0.05),基本达正常水平.结论:给孕鼠注射溴隐亭及IFN-γ抗体后,TGF-β1、IL-2、IL-4在血清及卵巢黄体的表达有一定改变,此改变可能与流产的发生有一定的关系.     

TGF-β1联合Wnt3a促进子宫内膜纤维化的机制研究

目的:探讨转化生长因子-β1(TGF-β1)与Wnt3a联合对子宫内膜基质细胞纤维化的促进作用。方法:原代分离培养人子宫内膜基质细胞(hESCs),将hESCs分为正常对照组和实验组(不同浓度TGF-β1),RT-PCR和Western blot法检测纤维化标记物(CollageⅠ、α-SMA、Fibronectin)及Wnt/β-catenin信号通路配体和核心分子的表达。筛选10ng/mL TGF-β1与100ng/mL Wnt3a联合作用hESCs,同法检测上述分子和Wnt/β-catenin核心分子的表达。结果:与正常对照组相比,TGF-β1诱导纤维化标记物(CollageⅠ、α-SMA、Fibronectin)、Wnt/β-catenin信号通路配体(Wnt3a)及核心分子(β-catenin、GSK-3β)和下游靶基因(CyclinD1、MMP-9)表达均升高;Wnt3a和TGF-β1联合诱导组纤维化标记物和Wnt/β-catenin信号通路核心分子表达显著高于对照组、Wnt3a组、TGF-β1组,差异均有统计学意义(P<0.05)。结论:Wnt3a联合TGF-β1激活Wnt/β-catenin信号通路促进子宫内膜基质细胞纤维化。     

邻苯二甲酸(2-乙基己基)酯对妊娠大鼠的影响及锌保护作用的研究

目的 探讨邻苯二甲酸(2-乙基己基)酯(DEHP)对大鼠妊娠结局的影响及锌对其影响的保护作用.方法 将50只雌鼠随机分为DEHP组(50mg·kg-1 ·d-1)、DEHP+锌组(含1.2 mg锌的葡萄糖酸锌+ 50 mg·kg-·d-1 DEHP)、空白组(灌注1ml生理盐水)、玉米油组(灌注1ml玉米油)、锌组(含1.2 mg锌的葡萄糖酸锌1ml)5组,每组10只,孕前7d开始每日给予相应药物灌胃,直至孕19 d处死孕鼠,取出胎鼠.测量孕鼠体质量、各脏器质量、活胎鼠数、活胎鼠体质量及胎盘质量.结果 孕鼠体质量及肾、脾、脑、心脏等脏器质量指数各组间两两比较,差异均无统计学意义(P＞0.05).孕鼠肝、子宫及卵巢质量指数,空白组分别为(4.4±0.7)％、(1.26±0.09)％、(0.083±0.009)％,玉米油组分别为(4.5±0.6)％、(1.29±0.10)％、(0.084±0.008)％,锌组分别为(4.4±0.4)％、(1.26±0.08)％、(0.084±0.009)％,DEHP组分别为(5.4±1.0)％、(1.11±0.08)％、(0.074±0.012)％,DEHP+锌组分别为(4.4±1.0)％、(1.28±0.10)％、(0.082±0.007)％,DEHP组与其他4组两两比较,差异均有统计学意义(P＜0.05),其他4组间两两比较,差异均无统计学意义(P＞0.05).活胎鼠数、活胎鼠体质量及胎盘质量,空白组分别为(12.8±2.7)只、(6.03±0.16)g、(1.00±0.03)g,玉米油组分别为(13.6±3.1)只、(6.07±0.20)g、(1.00±0.04)g,锌组分别为(13.3±3.1)只、(6.16 ±0.18)g、(1.00±0.05)g,DEHP组分别为(9.2±4.1)只、(4.03±0.09)g、(0.95±0.03)g,DEHP+锌组分别为(12.1±2.9)只、(6.09±0.17)g、(0.99±0.03)g,DEHP组与其他4组两两比较,差异均有统计学意义(P＜0.05),其他4组间两两比较,差异均无统计学意义(P＞0.05).结论 妊娠期DEHP的暴露可对孕鼠及胎鼠造成损伤,预先给予锌干预可减轻DEHP暴露对妊娠的影响,保护妊娠过程.     

妊娠中晚期大鼠耐热性碱性磷酸酶及胎盘超微结构在不同二氧化碳气腹作用时间下的变化

目的:探讨不同二氧化碳(CO2)气腹作用时间对妊娠中、晚期大鼠血浆耐热性碱性磷酸酶(HSAP)含量及胎盘超微结构的影响。方法:建立妊娠中期大鼠的CO2气腹模型,以气腹作用时间随机分为气腹0 h组(对照)、1 h组和2 h组,然后每组再随机分为2个亚组,即中孕组和晚孕组。用酶联免疫吸附测定法检测大鼠血浆HSAP含量,并用透射电子显微镜观察大鼠胎盘超微结构。结果:气腹1 h组孕中、晚期血浆HSAP值与同期对照组比较,差异无统计学意义(P>0.05);气腹2 h组孕晚期血浆HSAP值低于同期对照组,差异有统计学意义(P<0.05)。对照组及气腹1 h组孕中、晚期大鼠胎盘超微结构均为正常表现,气腹2 h组孕中期大鼠胎盘内质网扩张,线粒体肿胀、嵴断裂、空泡化,核内染色质异常分布;孕晚期大鼠胎盘游离缘表面微绒毛受损、排列紊乱,局部性脱失,胞质内细胞器减少,线粒体固缩变小。结论:气腹2 h组可导致妊娠中、晚期大鼠血浆HSAP下降及胎盘超微结构有缺氧表现,可能影响胎盘功能。     

邻苯二甲酸二(2-乙基已基)酯致隐睾大鼠表皮生长因子受体表达的实验研究

目的:探讨表皮生长因子受体(EGFR)在隐睾组织中是否存在改变及可能发挥的作用。方法:妊娠SD大鼠随机分为3组,即正常对照组、玉米油对照组和邻苯二甲酸二乙基已基酯(DEHP)实验组,每组10只。玉米油溶剂对照组和DEHP实验组自妊娠第12.5日到妊娠第19.5日分别持续每日经口给予玉米油或DEHP(500 mg/kg)1 ml灌胃,正常对照组不作任何处理。收集出生后20 d的雄性仔鼠睾丸,采用免疫组织化学及Western blotting方法检测EGFR在睾丸组织中的表达。结果:正常对照组和玉米油对照组EGFR的表达无统计学差异(P>0.05);DEHP诱导隐睾组隐睾睾丸组织中EGFR表达与2个对照组相比明显增加,差异有统计学意义(P<0.05)。结论:孕期暴露环境内分泌干扰物DEHP可引起雄性子代发生隐睾,雄性隐睾子代睾丸组织中EGFR表达增加,可能与隐睾引起的远期不育有关。     

Effects of blockade of the endothelin receptor A and inhibition of nitric oxide synthesis on uteroplacental and renal blood flow in awake pregnant rats

OBJECTIVE: The aim of this study was to evaluate the role of the ETA receptor and nitric oxide (NO) in the regulation of uteroplacental and renal blood flow in pregnant rats. STUDY DESIGN: Regional blood flows were measured by the microsphere technique in pregnant Sprague-Dawley rats (term 23 days). Blood flow was measured before and after ETA receptor blockade (BQ-123, 1 mg/kg) at gestational day (GD) 19 or 21 (n=8 and n=9, respectively). In 2 additional groups blood flow was measured before and after NO synthase inhibition (L-NAME 2 microg/min) at GD 19 or 21 (n=10 in each group). RESULTS: BQ-123 significantly increased placental and myometrial blood flows by almost 80% and 35%, respectively, at both gestational ages. BQ-123 did not alter renal blood flow. No effect on placental or myometrial blood flow was observed after L-NAME infusion, neither at GD 19 nor GD 21. Renal blood flow decreased by nearly 35% in both groups after L-NAME. CONCLUSION: There is an important role for endogenous ET in the regulation of uteroplacental blood flow in the rat. NO contributes to a significant vasodilatation in the renal vasculature; however, NO appears not to be involved in the maintenance of uteroplacental blood flow in the awake pregnant rat.     

Erythropoietin attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain

Periventricular leukomalacia (PVL), a common neonatal brain white matter (WM) lesion, is frequently associated with cerebral palsy. Growing evidence has indicated that in addition to ischemia/reperfusion injury, cytokine-induced brain injury associated with maternal or fetal infection may also play an important role in the pathogenesis of PVL. Recent studies have shown that administration of lipopolysaccharide (LPS) to pregnant rats causes enhanced expression of the cytokines, i.e., IL-1 beta, TNF-alpha, and IL-6, in fetal brains. In recent years, it has been shown that erythropoietin (EPO) has a critical role in the development, maintenance, protection and repair of the nervous system. In the present study we investigated the effect of EPO on LPS-induced WM injury in Sprague-Dawley rats. LPS (500 microg/kg) suspension in pyrogen-free saline was administered intraperitoneally to pregnant rats at 18 and 19 days of gestation. The control group was treated with pyrogen-free saline. They were given 5,000 U/kg recombinant human EPO. Seven-day-old Sprague-Dawley rat pups were divided into four groups: control group, LPS-treated group, prenatal maternal EPO-treated group (5,000 U/kg, intraperitoneally given to pregnant rats at 18 and 19 days of gestation), and postnatal EPO-treated group (5,000 U/kg, intraperitoneally given to 1-day-old rat pups). Cytokine induction in the postnatal 7-day-old (P7) rat brain after maternal administration of LPS was determined by the ELISA method. The proinflammatory cytokine levels (IL-1 beta, TNF-alpha, and IL-6) in P7 rat pup brains were significantly increased in the LPS-treated group as compared with the control group. Prenatal maternal EPO treatment significantly reduced the concentration of TNF-alpha and IL-6 in the newborn rat brain following LPS injection. The concentration of IL-1 beta was decreased in the intrauterine EPO treatment group. Postnatal EPO treatment significantly decreased only the IL-6 concentration in the newborn rat brain following LPS injection. The concentration of cytokines, IL-1 beta and TNF-alpha, was reduced in the postnatal EPO treatment group. We demonstrated here that LPS administration in pregnant rats at gestational day 18 and 19 induced WM injury in P7 progeny characterized by apoptosis. Prenatal maternal and postnatal EPO treatment significantly reduced the number of apoptotic cells in the periventricular WM. Using immunohistochemistry techniques, we investigated the effects of maternal administration of LPS on myelin basic protein (MBP) staining, as a marker of myelination in the periventricular area in the neonatal rat brain. MBP staining was significantly less and weaker in the brains of the LPS-treated group as compared with the prenatal maternal EPO-treated group. However, the postnatal EPO treatment did not prevent LPS-stimulated loss of MBP-positive staining. In conclusion, especially prenatal maternal EPO treatment attenuates LPS-induced injury by reducing the expression of inflammatory cytokines and sparing MBP in the neonatal rat brain. While the postnatal EPO treatment prevented LPS-induced brain injury this effect was partial. To our knowledge, this is the first study that demonstrates a protective effect of EPO on LPS-induced WM injury in the developing brain. Regarding the wide use of EPO in premature newborns, this agent maybe potentially beneficial in treating LPS-induced brain injury in the perinatal period.     

静脉注射免疫球蛋白对宫内感染胎鼠脑组织Toll样受体4表达影响的实验研究

目的观察静脉注射免疫球蛋白（IVIG）对围产期炎症暴露的胎鼠及子鼠脑组织Toll样受体4（TLR4）的影响。方法将40只SD大鼠孕鼠随机分成干预组、实验组、对照组3组。干预组16只于受孕第17天给予脂多糖（LPS）腹腔注射,剂量为350μg／kg,制备官内感染模型,取雌鼠后尾静脉,于造模成功后3h按2g／kg注射IVIG1次。实验组16只以相同的方法制备孕鼠宫内感染模型。对照组8只,在大鼠孕第17天给予等量生理盐水腹腔注射。取腹腔注射后的第24小时（孕第18天）、孕第19天、孕第21天以及生后1d。用苏木精-伊红染色法观察各组胎盘及各时间点脑组织的病理改变,比较各组胎鼠的体质量,用PCR法测得各组子鼠脑中TLR4-mRNA的含量,用免疫组织化学法观察各组各时间点脑组织TLR4的表达情况。结果实验组孕鼠胎盘及子宫壁充血水肿,白细胞浸润,子鼠脑白质水肿,并出现形态幼稚的细胞,甚至可见局灶性出血。实验组及干预组子鼠体质量出现不同程度减轻,与对照组比较,差异有统计学意义（P〈0．01）。实验组与干预组子鼠脑内TLR4-mRNA及TLR4的表达量在不同时间点出现不同程度的增高。结论宫内LPS感染可导致胎儿脑组织炎性反应,及时使用IVIG可以减少小胶质细胞的持续活化从而抑制胎儿脑组织的炎症反应,降低脑损伤的程度,达到脑保护的作用。     

双酚A对大鼠雌性子代卵巢发育和血管内皮生长因子蛋白表达的影响

目的:探讨大鼠妊娠期接触双酚A(BPA)对雌性子代卵巢发育和血管内皮生长因子(VEGF)蛋白表达的影响。方法:实验组于SD母鼠妊娠第7~20日分别灌胃给予0.005 mg/kg、0.05 mg/kg、0.5 mg/kg、2.5 mg/kg BPA,阴性对照组给予0.5 mg/kg溶剂,阳性对照组给予0.05 mg/kg己烯雌酚,每组8~10只。观察雌性仔鼠的阴道开口时间,分别于出生后30 d、60 d(分别相当于人青春期前和成年期)处死仔鼠,称重卵巢,光学显微镜观察卵巢组织学变化,ELISA检测血清雌、孕激素水平,Western blotting检测卵巢VEGF蛋白的表达。结果:BPA 0.05 mg/kg、0.5 mg/kg、2.5 mg/kg组仔鼠阴道开口时间明显缩短,2.5 mg/kg组青春期前仔鼠卵巢脏器系数明显升高,BPA 0.05 mg/kg、0.5 mg/kg、2.5 mg/kg组卵巢出现多囊样病变,BPA 0.5 mg/kg、2.5 mg/kg组青春期前仔鼠血清雌、孕激素水平明显升高,BPA 2.5 mg/kg可导致青春期前仔鼠卵巢VEGF蛋白表达明显升高。结论:母体妊娠期接触BPA可导致青春期前雌性仔鼠卵巢出现多囊样病变,但对成年雌性仔鼠卵巢无明显影响。     

On the mechanism of action of oral contraceptives. I. Effect of lynestrenol on ovum implantation and oviductal morphology in the rat

2 experiments on virgin female rats (average weight 200 gm) were performed to study the effects of small doses of lynestrenol on the early pregnancy of the rat. In both experiments, the rats were caged with a mate overnight and if, on the following morning, spermatozoa were found on the vaginal smear, that day became Day 1 of pregnancy. In Experiment 1, the test group (15) received .1 mg lynestrenol sc and the control group (14) 1 ml propyleneglycol on Days 2, 3, 4, and 5 of pregnancy. Experiment 2 differed in that the rats received 1 mg dosages of lynestrenol. On Day 7 of pregnancy, Experiment 1 rats were killed and their ovaries and genital tracts were examined. In Experiment 2, the rats were permitted to live until Day 23 to see if they would achieve full-term pregnancy. If delivery did not occur, they were killed (Day 25) and examined for fetuses. In Experiment 1, the dose did not significantly increase the number of lost ova (20% in controls), as indicated by the implanted embryos/recent corpora lutea ratio counted on Day 7. There was an increase in the number of ciliated cells in the epithelium and a diminution of the deciduoid tissue of the stroma. No histological changes were seen in the ovaries, embyros, or uteri. The 1 mg dosage of lynestrenol prevented pregnancy in all of the rats. Doses were smaller than those needed to inhibit ovulation, and the time of administration of the doses excluded any action on sperm transport, capacitation, or penetration. Lynestrenol would appear to act on the pregnant rat's genital tract, as oviducts displayed evidence of estrogen stimulation.     

邻苯二甲酸二(2-乙基己基)酯致胎鼠隐睾发生过程中胰岛素样因子3的表达分析

目的:探讨环境内分泌干扰物邻苯二甲酸二(2-乙基已基)酯[Di-(2-ethylhexyl)phthalate,DEHP]诱发胎鼠隐睾的分子机制。方法:妊娠昆明小鼠随机分为3组,每组15只:DEHP实验组(A组)、玉米油(溶剂)对照组(B组)和正常对照组(C组)。A组和B组自妊娠12.5￣18.5d分别持续经口每天给予DEHP(500mg/kg)或玉米油,C组不予灌药。结果:B组和C组睾丸组织中胰岛素样因子3(INSL3)mRNA和蛋白质的表达均无差异(P>0.05);A组INSL3mRNA的表达量约为B或C组的1/3,INSL3蛋白质的表达量约为B或C组的1/4,与B或C组比其差异显著(P<0.05)。A组睾丸引带发育不良,睾丸位置异常。结论:环境内分泌干扰物DEHP下调睾丸间质细胞INSL3基因的表达,影响睾丸引带发育,可能是DEHP诱发隐睾的分子机制之一。