促红细胞生成素及受体在妊娠维持中的作用

促红细胞生成素(EPO)是一类新发现的促血管生成因子,通过与其受体(EPOR)结合引发信号转导,具有促进血管生成、抗凋亡、抗缺氧作用,参与胎盘血管发生、肿瘤血管形成及转移等过程。EPO及EPOR在母-胎界面均有表达,对妊娠全过程起重要作用。妊娠过程中EPO/EPOR表达异常,可能与流产、子痫前期、胎儿生长受限等的发病有关。深入研究EPO在妊娠疾病中的作用,为妊娠疾病的诊断和治疗提供重要理论依据。     

促红细胞生成素及受体在妊娠维持中的作用

促红细胞生成素（EPO）是一类新发现的促血管生成因子,通过与其受体（EPOR）结合引发信号转导,具有促进血管生成、抗凋亡、抗缺氧作用,参与胎盘血．管发生、肿瘤血管形成及转移等过程。EPO及EPOR在母一胎界面均有表达,对妊娠全过程起重要作用。妊娠过程中EPO／EPOR表达异常,可能与流产、子痫前期、胎儿生长受限等的发病有关。深入研究EPO在妊娠疾病中的作用,为妊娠疾病的诊断和治疗提供重要理论依据。     

雄激素致不孕大鼠胰腺、下丘脑及卵巢雄激素受体mRNA表达

目的:研究雄激素致不孕大鼠(ASR)胰腺、下丘脑及卵巢组织中雄激素受体(AR)mRNA的含量变化。方法:9日龄SD雌性大鼠皮下注射丙酸睾丸酮制备ASR模型,于106日龄左右(动情前期)处死,取血放免法测定△4-雄烯二酮(△4-A)、总睾酮(TT)、游离睾酮(FT)、胰岛素(Ins)和C-肽(C-P),提取胰腺、下丘脑及卵巢总RNA,以单碱基突变模板为内对照的RT-PCR方法对ARmRNA进行定量分析。结果:ASR模型血△4-A、TT、FT、Ins、C-P均显著高于对照组(P<0.05,P<0.01),胰腺、下丘脑及卵巢的AR mRNA表达水平明显升高,与对照组相比差异有统计学意义(P<0.05,P<0.01)。结论:ASR模型血雄激素水平升高,上调胰腺、下丘脑及卵巢AR mRNA的表达,引起该模型的高胰岛素血症和无排卵。     

人β防御素3在胎膜早破妊娠妇女中的表达及其意义

目的:探讨人β防御素3(h BD3)在胎膜早破妊娠妇女中的表达及其临床意义。方法:随机选择2013年1—12月于湖北省孝感市中心医院妇产科住院分娩的初产胎膜早破患者45例作为胎膜早破组,取同期正常妊娠妇女45例作为对照组。应用免疫组织化学SP法检测胎膜组织中h BD3的表达,酶联免疫吸附法检测血清肿瘤坏死因子α(TNF-α)和h BD3的含量。结果:胎膜早破组h BD3阳性33例;对照组h BD3阳性13例,2组阳性率比较差异有统计学意义(P0.05);与对照组比较,胎膜早破组血清TNF-α、h BD3在入院及分娩时均升高(P0.05),且胎膜早破组分娩时血清TNF-α、h BD3较入院时均升高(P0.05)。结论:胎膜早破时h BD3可能是在TNF-α的介导下参与了抗微生物的天然免疫反应。     

原纤维蛋白-1 mRNA和蛋白在子宫肌瘤组织中的表达

目的：探讨原纤维蛋白-1(fibrillin-1,FBN-1)mRNA和蛋白在子宫肌瘤组织中的表达及其与月经周期的关系。方法：50份子宫肌瘤及同源正常子宫平滑肌组织标本在术中被采集。根据月经周期及子宫内膜组织病理学检查分为增生期、分泌期及萎缩期。采用实时荧光定量PCR、Western blot分析及免疫组织化学方法检测FBN-1 mRNA和蛋白的表达。结果：免疫组织化学染色显示FBN-1在子宫肌瘤及正常子宫平滑肌组织的细胞外基质中均有较丰富的表达。FBN-1 mRNA和蛋白在增生期和分泌期中的子宫肌瘤组织中的表达均明显高于同源正常子宫平滑肌组织(P＜0．01,P＜0．05；P＜0．01,P＜0．05),而在绝经期中的子宫平滑肌瘤及正常子宫平滑肌组织的表达无明显差异。结论：FBN-1可能与子宫肌瘤的发生机制有关,并可能受激素调节的影响。     

Thromboxane Receptor Blockade Causes Acidemia in the Ovine Fetus

The placenta produces the vasoactive eicosanoids thromboxane and prostacyclin. We hypothesized that fetal administration of SQ 29,548, a thromboxane receptor blocker, would lack direct cardiorespiratory effects in the ovine fetus. Continuous monitoring of maternal and fetal heart rates, blood pressures, and common umbilical artery blood flow was performed in six chronically catheterized pregnant ewes. Serial maternal and fetal arterial blood gases and serum lactates were obtained. After 120 minutes of infusion, a significant decrease in fetal mean arterial pressure and a significant increase in fetal heart rate was observed. A significant decrease in fetal arterial pH (7.41 ± 0.02 to 7.33 ± 0.02), PO₂ (26.8 ± 3.2 to 19.8 ± 3.4), HCO₃^? (27.2 ± 1.5 to 24.9 ± 2.0), and base excess (2.9 ± 1.6 to 0.2 ± 2.3) with a significant elevation in PCO₂ (45.4 ± 2.6 to 50.1 ± 3.3) occurred after 120 minutes of SQ 29,548 infusion. SQ 29,548 infusion caused a significant decrease in common umbilical artery flow, from 249.4 ± 19.4 ml ± min^?1 ·; kg^?1 fetal weight to 178.3 ± 17.9 ml · min^?1 · kg^?1 fetal weight at 120 minutes. Fetal blood lactate levels were significantly elevated from 22.0 ± 3.1 to 54.1 ± 3.8 mg/dL after 120 minutes of SQ 29,548 infusion. Prolonged infusion of SQ 29,548 results in umbilical-placental hypoperfusion and significant alterations in acid-base balance in the ovine fetus.     

Expression of Aquaporin 1 and Aquaporin 3 in Fetal Membranes and Placenta in Human Term Pregnancies with Oligohydramnios

ObjectiveTo explore the pathophysiology of oligohydramnios, the association between the expression of aquaporin 1 and aquaporin 3 in fetal membranes and placenta and oligohydramnios was investigated.MethodsSixty patients underwent elective cesarean sections at term were studied, 30 patients with isolated oligohydramnios and the other 30 with normal amniotic fluid volume (AFV). Real-time polymerase chain reaction and immunohistochemistry were employed to determine expression and localization of aquaporin 1 and aquaporin 3 in amnion, chorion and placenta, respectively.ResultsThe expression of aquaporin 1 and aquaporin 3 was detected in amnion, chorion and placenta using real-time RT-PCR. By immunohistochemistry, aquaporin 1 and aquaporin 3 protein expressions in amnion epithelia and chorion cytotrophoblasts were identified. In placenta, aquaporin 1 was detected in placental vessels, while aquaporin 3 was found in trophoblast cells. In comparison to normal AFV group, there was a significant decrease of aquaporin 1 expression in amnion in oligohydramnios group, but no significant difference in chorion and placenta between the two groups. The expression of the aquaporin 3 in amnion and chorion in oligohydramnios group was significantly decreased, while expression in placenta was significantly increased compared with that in normal AFV group.ConclusionsAlteration of aquaporin 1 and aquaporin 3 expression in fetal membranes and placenta may be important in the pathophysiology of isolated oligohydramnios.     

Prostaglandin E2, Fetal Maturation and Ovine Parturition

Summary: The major source of PGE₂ in ovine pregnancy is the placenta, with secretion occurring bidirectionally into fetal and maternal circulations. The placental output of PGE₂ appears to increase when demand on placental function is increased, suggesting that the normally observed increase in its concentration towards term is driven by the growing demands of the fetus. The fetal pituitary is also involved in the control of PGE₂ synthesis. PGE₂ has potent stimulatory actions on the fetal pituitary to increase both the absolute concentration and the bioactive fraction of ACTH-containing peptides in the fetal circulation. It also directly stimulates glucocorticoid secretion from the fetal adrenal gland.
We propose that PGE₂ provides a tonic stimulation of the fetal HPA axis in late gestation, contributing to phenomena such as the apparent insensitivity of the pituitary to Cortisol feedback and the increasing sensitivity of the fetal adrenal. Because of its apparent responsiveness to placental workload, it may transduce stimuli from the placenta and transmit them to the fetal HPA axis, giving a possible biochemical basis to the empirically observed correlation between fetal metabolic demand and gestation length.     

青海地区子痫前期患者HLA-GmRNA及蛋白表达研究

目的:探讨青海高原地区子痫前期患者人类白细胞相关抗原G(HLA-G)mRNA、蛋白表达情况及临床意义。方法:收集2011年9月至2011年12月在青海大学附属医院产科分娩的30例子痫前期患者和30例正常妊娠妇女的胎盘组织和血清样品,采用实时荧光定量PCR及West-ernblot分析检测HLA-GmRNA和蛋白在正常妊娠与子痫前期患者胎盘中的表达差异,并应用双抗体夹心酶联免疫吸附法(ELISA)检测血清中可溶性HLA-G的表达。结果:①青海高原地区子痫前期患者胎盘组织中HLA-GmRNA、蛋白表达水平明显低于正常妊娠组,差异有统计学意义(P<0.05)。②子痫前期患者血清中可溶型HLA-G(sHLA-G)浓度明显低于正常妊娠组,差异有统计学意义(P<0.05)。结论:HLA-G基因转录的下调及其蛋白质表达下降,在青海高原地区子痫前期的发生发展过程中可能发挥重要作用。     

Differential Expression of Fibulin Family Proteins in the Para-cervical Weak Zone and Other Areas of Human Fetal Membranes

ObjectiveHuman fetal membranes (FM) at term have been shown to contain a weak zone in the region overlying the cervix which exhibits characteristics of increased collagen remodeling and apoptosis. It has been hypothesized that the FM rupture initiation site is within this weak zone. Although the FM weak zone has been partially characterized, it is unclear what structural differences in the extracellular matrix result in its decreased rupture strength. A screen for differentially expressed proteins in the amnion of the weak zone versus other FM areas demonstrated that fibulin 1 was decreased. We investigated potential regional differences in all fibulin protein family members.MethodsFM fibulins were localized by immunohistochemistry. Detected fibulins were screened by Western blot for differences in abundance in the amnion of the weak zone versus non-weak zone FM regions. Amnion epithelial and mesenchymal cells were also screened for fibulin production.ResultsFibulins 1 and 5 were detected in the cytoplasm of and in a pericellular pattern surrounding all FM cells, and in a dense extracellular pattern in the amniotic compact zone. Fibulin 3 was detected within the cytoplasm of amnion epithelial and chorion trophoblast cells. Fibulins 2 and 4 were not detected. Fibulins 1, 3 and 5 demonstrated decreased abundance of 33%, 63% and 58% (all P < 0.01) in amnion of the weak zone relative to other FM regions. Amnion cells produced all three detected fibulins. Furthermore, TNF inhibited amnion cell fibulin production in a dose dependent manner.ConclusionFibulins 1, 3 and 5 were localized coincident with major microfibrillar networks in amnion. Each showed decreased abundance in the amnion component of the FM weak zone. Amnion epithelial and mesenchymal cells produced all three fibulins and their abundance was inhibited by TNF. We speculate that the amnion microfibrillar layer undergoes significant remodeling with the development of the FM weak zone.     

Pregnancy-Promoting Actions of HCG in Human Myometrium and Fetal Membranes

Human chorionic gonadotropin (HCG) plays a major role in early human development through a series of well recognized pregnancy-promoting actions that are exerted in the first trimester, including maternal recognition of pregnancy, enhancement of embryo implantation and survival, stimulation of trophoblast growth and differentiation, and prolongation of the functional life of the corpus luteum. Recent research indicates that HCG can exert significant pregnancy-promoting actions also in the remainder of pregnancy through its effect on the myometrium and on fetal membranes. In the myometrium, HCG promotes the inhibition of smooth muscle cell contractility through several mechanisms, including inhibition of gap junction formation, reduction of intracellular calcium concentration, increase in the expression of progesterone receptor, and an increase in the expression of phosphodiesterase 5 (PDE5), an enzyme controlling the intracellular levels of cGMP. This effect appears to be specific for PDE5 since it has not been found for other hormones potentially involved in pregnancy such as estrogen, progesterone and thyroid hormone. In fetal membranes, HCG can modulate expression of the inducible isoform of nitric oxide synthase (iNOS), as well as specific immunoregulatory cytokines such as the high mobility group box 1 (HMGB1) protein. This accumulating evidence suggests that HCG has a wide spread pregnancy-promoting actions that are exerted in various reproductive and gestational tissues.     

Effect of Oxymorphone Hydrochloride on Ovine Fetal Heart Rate Variability

In order to determine the effect of the narcotic analgesic oxymorphone hydrochloride (Numorphan, DuPont) on fetal heart rate (FHR) variability, mathematical indices of short-term and long-term FHR variability were determined continuously from R–R intervals of the electrocardiogram in eight chronically instrumented ovine fetuses for 60 min before and after a maternal intravenous bolus of 0.04 mg/kg oxymorphone. The index of short-term variability decreased from 12.7 ± 2.0 during control to 9.7 ± 1.7 during the period from 10 to 30 min after oxymorphone administration during periods of low-voltage, high-frequency electrocortical activity (LVHF ECoG) (P < 0.05). Mean FHR was decreased from 169 ± 8 beats per minute (bpm) during control to 155 ± 7 bpm 30 to 50 min after oxymorphone (P < 0.05). Fetal electrocortical activity was also determined and the decrease in FHR short-term variability occurred despite an increase in the percent time spent in LVHF electrocortical activity from 53 ± 4% during the control period to 74 ± 5% after the oxymorphone injection (P < 0.05). Long-term FHR variability was unaffected by the oxymorphone administration. This study indicates that maternal administration of oxymorphone hydrochloride causes decreased short-term fetal heart rate variability in sheep.     

热休克蛋白40 mRNA在卵巢上皮性癌中的表达及意义

目的:了解热休克蛋白40(heat shocking protein,Hsp 40)mRNA在卵巢上皮性癌组织中的表达,并分析其与临床病理资料之间的关系.方法:用RT-PCR技术检测40份卵巢上皮性癌组织、20份卵巢良性肿瘤组织、15份正常卵巢组织中Hsp 40 mRNA的表达情况并进行半定量比较,将其表达结果与临床病理资料进行统计学分析.结果:Hsp 40 mRNA在卵巢上皮性癌、卵巢良性肿瘤及正常卵巢组织中均有表达,但在卵巢上皮性癌组织中的相对表达水平明显高于卵巢良性肿瘤组织(P<0.01)及正常卵巢组织(P<0.01),差异有高度统计学意义;卵巢良性肿瘤组织中Hsp 40 mRNA的相对表达水平高于正常卵巢组织,差异有高度统计学意义(P<0.01).Hsp 40 mRNA的表达与组织类型、临床分期、病理分级无相关性.结论:Hsp 40 mRNA的表达可能与卵巢上皮性癌的发生、发展有关.     

基质金属蛋白酶2,9在胎膜早破产妇胎膜的表达变化

目的:探讨基质金属蛋白酶- 2、- 9(MMP - 2、MMP - 9)在胎膜早破(PROM)发病机制中的作用。方法:选择早产PROM(PPROM)产妇1 1例、足月PROM产妇32例及足月临产产妇1 6例作为研究组,1 1例足月未临产产妇作为对照组;采用免疫组织化学法检测胎膜宫颈部和宫体部中MMP 2及MMP - 9的分布与表达。结果:①各研究组宫颈部胎膜MMP 2的表达均高于同组宫体部(P <0 .0 5 ) ;胎膜(宫颈部和宫体部)MMP - 2的表达在两PROM组间无差异(P >0 .0 5 ) ,但均高于足月临产组和对照组(P <0 .0 1 )。②MMP - 9在对照组中未见表达;MMP - 9在研究组胎膜宫颈部的表达均明显高于宫体部(P <0 .0 1 ) ,其中PPROM组宫颈部胎膜MMP 9表达的IH积分明显高于其余各组(P <0 .0 1 )。③胎膜宫颈部MMP - 2的表达与MMP 9的表达呈正相关(P =0 .0 0 0 )。结论:MMP -2和MMP - 9参与了产程中胎膜的破裂,在PROM的发病机制中起着重要的作用,其中MMP - 9在PPROM发病机制中的作用更为重要。     

胎盘OB mRNA表达与胎儿体重调控机制的初步研究

目的　检测不同胎龄和不同出生体重儿的胎盘组织肥胖基因 (obese,OB) m RNA的表达以及对母儿血 leptin(瘦素 )的影响 ,初步分析胎盘瘦素在围产期调控胎儿体重及维持正常妊娠的机制。　方法　随机选取正常分娩的母儿血及其胎盘组织 6 0例 ,根据胎龄分为 :2 9～ 30周 5例 ,～ 32周 6例 ,～ 34周 7例 ,～ 36周 10例 ,37周～ 32例。根据新生儿体重分为 :10 0 0～ 1999g9例 ,～2 999g2 1例 ,～ 3999g30例 ,分别采用放射免疫法及 RT- PCR技术 ,检测母儿血瘦素水平及胎盘组织 OB m RNA表达。　结果　随胎龄增加胎盘 OB m RNA的表达量逐渐下降 ,早产儿明显高于足月儿 (0 .30± 0 .19与 0 .0 9± 0 .0 5 ,P<0 .0 1) ,不同体重胎盘 OB m RNA的表达量差异性有显著 (根据体重分组 ,分别为 0 .4 7± 0 .16 ,0 .2 1± 0 .15 ,0 .0 9± 0 .0 5 ,P<0 .0 0 1)。胎盘 OB m RNA的表达量与母儿血瘦素水平、出生体重、胎龄、胎盘重量呈负相关。　结论　胎盘 OB m RNA的表达量随胎龄、体重增加逐渐下降 ,提示胎盘合成、分泌的瘦素可能作为一种外源性瘦素 ,在妊娠过程中对母儿体内内源性瘦素的产生起着重要的负调控作用 ,为胎儿体重增加和适应宫外环境提供保障。     

胎膜早破发病机制的研究进展

胎膜早破（premature rupture of fetal membranes,PROM）是产科临床非常普遍且相当棘手的问题,是早产的常见原因,若不能合理处理,母儿的生命就会受到威胁。引起胎膜早破的原因众多,其发病机制也十分复杂。综述胎膜破口区域的组织学特征,包括传统病理学和新型光学研究观察结果;其次介绍新发现的胎膜存在微小裂隙并持续重塑的观点;另外部分早破胎膜破口有发生自发性愈合,总结胎膜破口自愈现象的机制,主要是以细胞迁移为基础的物理性封闭;PROM发生机制一直以来都是研究热点,介绍当下较新的理论如胎膜老化和胎膜氧化应激失衡研究进展,同时对胎膜细胞凋亡、胎膜蛋白酶系统/抗蛋白酶系统平衡失调等传统理论的新近研究加以综述,旨在为胎膜早破进一步研究提供理论思路。     

Expression of Retinoblastoma Tumor Suppressor Gene Protein, Epidermal Growth Factor Receptor, and c-erbB-2 Oncoprotein in Primary Vaginal Carcinomas

Forty-six primary vaginal carcinomas were examined immunohistochemically for expression of retinoblastoma (RB) protein, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoprotein. The results demonstrated that RB protein was not lost in any of the cases, suggesting that structural abnormalities of the RB gene may not play an important role in the pathogenesis of vaginal carcinoma. Fifteen and 11% of the cases showed increased expression of EGFR and c-erbB-2 oncoprotein, respectively, indicating that these oncoproteins may be involved in the neoplastic process of a minority of vaginal carcinomas. Overexpression of EGFR and c-erbB-2 oncoprotein had no prognostic significance in vaginal carcinomas.     

细胞凋亡与胎膜早破的相关性研究

目的:探讨细胞凋亡增加是否为胎膜早破的一个发病机理或危险因素。方法:随机采集临产前剖宫产分娩的初产妇肘静脉血、羊水及胎膜,其中胎膜早破者34例,正常完好胎膜17例。①用ELISA测定各组血清、羊水中TNF-α的浓度:②用TUNEL原位标记术精确测定各组胎膜细胞凋亡指数;③用免疫组化法检测各组胎膜组织中Bax、Bcl-2、Fas、Caspase-3表达情况。结果:①胎膜早破组血清、羊水中TNF-α浓度明显高于正常对照组水平(P<0.001);且血清、羊水中TNF-α浓度有相关性,r=0.386。胎膜感染组血清、羊水中TNF-α浓度较无感染组高(P<0.001)。②胎膜早破组胎膜感染发生率高于对照组(P<0.05)。③胎膜早破组细胞凋亡指数明显高于正常组(P<0.001);感染组细胞凋亡指数较无感染组高(P<0.001)。④胎膜早破组促凋亡蛋白Bax、Fas、Caspase-3阳性表达率高于对照组(P<0.05),但抑凋亡蛋白Bcl-2阳性表达率两组间无统计学差异(P>0.05);胎膜感染组Bax、Bcl-2、Caspase-3阳性表达率与无感染组比较无统计学差异(P>0.05),但感染组Fas阳性表达率高于无感染组(P<0.05)。结论:基因、环境因素相互作用下的细胞凋亡增加可能是胎膜早破的一个重要发病机制,可独立致病,亦或与其他相关危险因素(如感染)协同致病。