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。     

血管生成素与妊娠

血管生成素（Angs）是一类新发现的促血管生成因子,具有调节血管生成、退化及血管稳定性的作用,参与胚胎血管的发育、肿瘤血管的生成及转移等过程。目前研究较多的是Ang-1和Ang-2,二者结构相似而功能各异,共同受体为酪氨酸激酶-2受体（Tie-2）。Angs及其受体存在于胎盘组织及胎儿体内,在妊娠整个过程中均可表达,对于妊娠全过程起重要作用。妊娠疾病中Angs／Tie系统基因表达失控,可能与子痫前期、胎儿生长受限等妊娠疾病的发病过程有关,深入研究Angs在妊娠疾病中的作用．将为临床上妊娠疾病的诊断和治疗提供重要的理论依据。     

血管生成素与妊娠

血管生成素(Angs)是一类新发现的促血管生成因子,具有调节血管生成、退化及血管稳定性的作用,参与胚胎血管的发育、肿瘤血管的生成及转移等过程.目前研究较多的是Ang-1和Ang-2,二者结构相似而功能各异,共同受体为酪氨酸激酶-2受体(Tie-2).Angs及其受体存在于胎盘组织及胎儿体内,在妊娠整个过程中均可表达,对于妊娠全过程起重要作用.妊娠疾病中Angs/Tie系统基因表达失控,可能与子痫前期、胎儿生长受限等妊娠疾病的发病过程有关,深入研究Angs在妊娠疾病中的作用,将为临床上妊娠疾病的诊断和治疗提供重要的理论依据.     

促红细胞生成素对谷氨酸致培养皮层神经细胞损伤的保护作用

新生儿缺氧缺血性脑病（hypoxic—ischemic encaphalopathy，HIE）是导致儿童伤残的重要疾病之一。谷氨酸（glutamate，Glu）的大量释放是其神经细胞损伤的主要原因。促红细胞生成素（erythropoitin，EPO）是近年来发现的神经保护因子，具有神经营养、抗凋亡、抗兴奋性氨基酸毒性和抗炎症等作用。本实验目的在于观察EPO对Glu兴奋性神经毒性的影响。     

血管生成素与妊娠

血管生成素(Angs)是近年来研究发现的一组促血管生成的调节因子,由血管内皮细胞分泌,其在血管的发生、发展过程中发挥着重要的作用。Ang-1和Ang-2促进肿瘤血管的生成和肿瘤细胞的浸润,妊娠过程中,胚胎的植入和肿瘤的浸润过程是相似的,Angs及其受体酪氨酸激酶-2受体(Tie-2)在胎盘和胎儿中都有表达,对胚胎的植入、胎盘血管的生成以及胎儿的生长发育都有重要的作用。因此,在妊娠过程中,如果任何一个环节出现血管生成障碍,将会导致胚胎植入失败或妊娠并发症等的发生。对Angs对妊娠作用的进一步研究,将有助于妊娠期疾病的诊断、治疗。     

芳香烃受体(AHR)在胎盘生成中的作用

胎盘是连接母体与胎儿的重要器官,在维持正常的妊娠过程中发挥着重要的作用。胎盘的结构和功能异常不仅易引发妊娠期高血压和糖尿病等妊娠并发症,还易导致早产、胎儿宫内生长受限(intrauterine growth retardation,IUGR)、流产等不良妊娠结局。芳香烃受体(aryl hydrocarbon receptor,AHR)作为一种配体激活性转录蛋白,参与了生殖调控、免疫功能调节、血管重塑等一系列重要的生理活动。AHR与滋养细胞的增殖和凋亡密切相关,并且具有调节滋养细胞细胞周期的作用。AHR在胎盘血管的生成及血流量的调节中也发挥着重要的作用,它通过调节促血管生成因子与血管生成抑制因子的平衡,参与胎盘血管的正常发育生长;同时AHR还很可能在胎盘的生长发育中介导了胎盘血管的生成以及滋养细胞的侵袭能力;AHR表达异常直接导致了相关妊娠期疾病的发生。     

血小板衍生内皮细胞生长因子的研究进展

内皮细胞的生长、血管的生成、维持适度的凋亡是许多生理过程所必须的环节.调节这些过程的因子表达异常,将导致多种病理过程的发生,进而引发多种疾病.血小板衍生内皮细胞生长因子(PD-ECGF)即胸磷酸化酶,是血管生成研究领域相对较新的一个细胞生长因子,是血小板中唯一的一种内皮细胞生长因子.其分布广泛,具有刺激内皮细胞生长、促血管生成及抗凋亡作用.其表达的程度与微血管密度关系密切,呈显著正相关.在许多血管生成相关性疾病的发生发展中起着至关重要的作用.明确其表达及其影响因素,可能为某些疾病得到早期的预防和治疗提供新思路、新途径.     

子宫内膜异位症抗血管生成研究进展

血管生成在子宫内膜异位症（EMs）的发病过程中起重要作用。过去10年中,越来越多的研究将重点集中在抗血管生成方面,现已证实许多化学物质对子宫内膜异位病灶有抗血管生成的作用,包括生长因子抑制剂、内源性血管生成抑制剂、他汀类药物、环氧化酶-2（COX-2）抑制剂、免疫调节剂、多巴胺受体激动剂和过氧化物酶体增殖激活受体（PPAR）激动剂等。现将EMs抗血管生成的研究进展加以概括总结,并探讨抗血管生成物质治疗EMs的潜在作用。     

血小板衍生内皮细胞生长因子的研究进展

内皮细胞的生长、血管的生成、维持适度的凋亡是许多生理过程所必须的环节。调节这些过程的因子表达异常,将导致多种病理过程的发生,进而引发多种疾病。血小板衍生内皮细胞生长因子(PD-ECGF)即胸磷酸化酶,是血管生成研究领域相对较新的一个细胞生长因子,是血小板中唯一的一种内皮细胞生长因子。其分布广泛,具有刺激内皮细胞生长、促血管生成及抗凋亡作用。其表达的程度与微血管密度关系密切,呈显著正相关。在许多血管生成相关性疾病的发生发展中起着至关重要的作用。明确其表达及其影响因素,可能为某些疾病得到早期的预防和治疗提供新思路、新途径。     

glycodelin与妊娠及其相关疾病的关系

妊娠相关子宫内膜蛋白glycodelin是一组糖蛋白,属于脂质载体蛋白lipocalin超家族。目前发现有4种亚型,分别具有不同的生理作用。glycodelin在人体内多种组织中有表达,其表达水平受到多种因素的调控,主要在免疫抑制、诱导细胞分化、促血管生成以及调节精子与透明带的结合等方面发挥作用。随着研究的深入,发现其在妊娠过程中发挥重要作用,并与部分妊娠相关疾病如流产、异位妊娠、子痫前期、妊娠期糖代谢异常等关系密切。就近年glycodelin的相关研究作一综述。     

Placental expression of erythropoietin mRNA, protein and receptor in sheep

In ovine placentae at 100 days gestation, we localized the expression of erythropoietin (EPO) mRNA by in situ hybridization and determined the cellular localization of EPO protein and EPO receptor protein by fluorescence immunohistochemistry. Erythropoietin mRNA was observed in maternal tissue at the apical tips of the fetal cytotrophoblastic villi at their interface with the maternal caruncle and was absent from both the centrally located fetal-maternal tissue and the more peripherally located maternal caruncle. An EPO-protein-associated fluorescent signal was observed in the same interface region as the EPO mRNA hybridization signal. An intense fluorescent signal associated with EPO receptor protein was observed in the apical fetal-maternal interface region with a lower density signal dispersed throughout the remainder of the interdigitating fetal-maternal tissue. The predominant cells in the apical fetal-maternal interface were identified as binucleate cells by immunohistochemistry. Thus the localization of the binucleate cells was the same as that for the EPO mRNA and the EPO protein, whereas the EPO receptor had a more generalized distribution. Since the binucleate cells are hormone producing cells, we speculate that the binucleate cells are the source of the EPO that is present in ovine placenta.     

神经纤毛蛋白-1与肿瘤血管生成的关系

神经纤毛蛋白-1（Neuropilin-1,NRP-1）属跨膜糖蛋白,作为轴突导向分子（semaphorin,Sema）的受体．参与神经导向的调节。同时作为血管内皮生长因子受体2（vascular endothelial growth factor receptor2,VEGFR-2）的共受体表达于血管内皮细胞,参与血管新生的调节。近年已基本阐明NRP-1在神经系统中的作用,其在血管新生方面的研究亦逐渐深入。NRP-I可通过依赖血管内皮生长因子（VEGF）的方式或独立的方式参与肿瘤血管新生调节．同时在肿瘤生长及转移中发挥重要作用。NRP-1生物学特性取决于其独特的分子结构。综述NRP-l结构和生物学特性、与VEGF及其受体的相互作用、对肿瘤血管新生的影响及其在妇科肿瘤中的研究。     

Erythropoietin receptor-like immunostaining on human spermatozoa

This study aimed to demonstrate the presence of erythropoietin (EPO) receptor on spermatozoa. Whole ejaculates of four healthy volunteers were incubated with polyclonal rabbit anti-EPO receptor and subsequently stained with a Cy-3 labelled secondary antibody. Four slides per subject were analysed, no staining was observed in slides incubated with either primary or secondary antibody alone. EPO receptor staining was positive in 92±8% of EPO pre-treated and 91±4% of non-treated sperm cells. The results suggest that spermatozoa express EPO receptor on plasma membrane, which might act to protect these cells from damage after ejaculation.     

Erythropoietin receptor expression in biopsy specimens from patients with uterine cervix squamous cell carcinoma

Hypoxia, an important mechanism of radioresistance, is a strong stimulus for erythropoietin (EPO) production. The stimulatory effects of EPO are mediated through the activation of its receptors, EPO receptors (EPORs). The objective of this study is to determine whether EPORs are expressed in biopsy specimens of patients with squamous cell carcinoma of the cervix. Eighteen biopsy specimens were studied after obtaining Institutional Review Board-approved consent. Standard immunohistochemistry techniques were utilized. Expression of EPORs was present in 16 out of 18 (88.9%) specimens. The intensity (qualitative) and the frequency (semiquantitative) of EPORs expression showed a statistically significant correlation (P= 0.00379). Statistical analysis was performed to determine whether EPORs expression is related to other parameters such as age, FIGO stage, histologic grade, and hemoglobin levels. Only age showed a statistically significant correlation with EPORs frequency of expression (P= 0.00878). Currently, work is in progress in our laboratory to study the radiobiologic effects of EPO on the radiation response of cultured cancer cell lines in vitro.     

妊娠期糖尿病患者氧化应激和EPO、FNRBC水平变化与胎盘组织学改变的关系

目的:探讨妊娠期糖尿病(GDM)患者氧化应激状态与脐血促红细胞生成素(EPO)和胎儿有核红细胞(FNRBC)水平变化及其与胎盘组织形态学异常发生率的关系。方法:选取28例GDM患者(GDM组)和22例正常妊娠妇女(正常对照组),采集其母血和脐血及对应的胎盘标本,检测母血和脐血氧化应激标志物丙二醛(MDA)、超氧化物歧化酶(SOD)浓度,脐血EPO浓度和FNRBC计数,同时对胎盘组织进行病理学检测。结果:GDM组患者母血和脐血中的MDA及脐血中EPO浓度和FNRBC计数明显高于正常对照组(P<0.05),SOD浓度较正常对照组明显降低(P<0.05)。GDM组患者胎盘病理检查提示,与正常对照组相比:绒毛成熟不良、干绒毛小动脉增厚和绒毛间质毛细血管充盈明显的发生比例增加(P<0.05),并且母血和脐血中的MDA浓度与胎盘绒毛成熟不良的发生比例呈正相关(P均<0.05)。结论:胎盘绒毛发育和成熟的复杂过程可能受母胎氧化应激与抗氧化环境的影响,胎盘病理组织学显示GDM时绒毛血管发育与成熟的异常可能导致胎儿缺氧和不良后果。     

Increased hyaluronan and CD44 expressions in intravenous leiomyomatosis

BACKGROUND: To determine the influence of hyaluronan and its receptor CD44 in the angiogenesis and invasiveness of intravenous leiomyomatosis (IVL). METHODS: Paraffin-embedded sections from four IVL cases and 10 uterine leiomyoma cases were immunohistochemically stained for CD34, CD44, basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and platelet-derived growth factor and assayed for microvessel densities. Hyaluronan was immunostained by biotinylated hyaluronan-binding peptide and the results were clinically correlated. RESULTS: CD34 labeling showed significantly increased microvessel counts in IVL (156.6+/-3.7), when compared to uterine leiomyomas (61.3+/-27.3; P<0.001). Hyaluronan and its receptor CD44 were prominently expressed in IVL when compared to leiomyomas and associated with an elevation in bFGF expression. CONCLUSIONS: IVL is a highly vascular neoplasm with elevated microvessel counts. The increase of hyaluronan and CD44 expression in IVL suggests that it is highly angiogenic and has an invasive potential. Elevation of hyaluronan may play a possible role in the pathogenesis of IVL.     

环氧合酶-2对宫颈癌淋巴管生成及预后的影响

目的:研究环氧合酶-2(Cox-2)在宫颈癌中的表达并探讨其对淋巴管生成及预后的影响。方法:用免疫组化SP法,分析59例宫颈癌石蜡标本中Cox-2、血管内皮生长因子-C(VEGF-C)及其受体VEGFR-3蛋白表达,并对微淋巴管密度行定量分析。结果:Cox-2蛋白在86.4%(51/59)的病例中呈阳性表达,与VEGF-C表达[66.1%(39/59)]呈显著正相关(r=0.424,P<0.001),且与淋巴结转移、术后生存期缩短有关;在Cox-2表达阳性组淋巴管密度明显高于阴性组(P=0.013)。结论:在宫颈癌中Cox-2可能上调VEGF-C表达,通过促进淋巴管生成与淋巴结转移有关。检测Cox-2可作为预测宫颈癌患者预后的一项指标。     

VEGF-C及受体VEGFR-3在宫颈癌中的表达及临床意义

目的:研究宫颈癌组织中血管内皮生长因子C(VEGF-C)及其受体VEGFR-3的表达并探讨其与淋巴结转移、预后的关系。方法:采用免疫组化SP法,分析59例石蜡标本中VEGF-C、VEGFR-3蛋白表达情况,并应用计算机辅助图象分析系统对脉管的面积进行定量分析。结果:宫颈癌组织中VEGF-C蛋白表达率为66.1%(39/59),与淋巴结转移显著正相关(P=0.005)。VEGF-C阳性组5年生存率显著低于阴性组(P=0.006)。VEGFR-3表达主要定位在脉管结构,VEGFR-3阳性脉管密度在VEGF-C表达阳性组明显高于阴性组(P=0.015),淋巴结转移组明显高于无转移组(P=0.001)。结论:VEGF-C通过促进宫颈癌内淋巴管形成,促进淋巴转移并与患者的预后有关。     

Plasminogen activators and inhibitors are transcribed during early macaque implantation

Plasminogen activators and inhibitors may be important early in primate implantation but evidence for this is sparse in non-human primates. We define the expression of urokinase type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and type 2 (PAI-2), the receptor for uPA (uPAR) and fibrin/fibrinogen in monkey implantation sites. In situ hybridization and immuno-histochemical localization of rhesus monkey implantation sites (day 15-16 postovulation) indicate: (1) uPA mRNA is localized to placental trophoblast, epithelial plaque and endometrial stroma. (2) tPA mRNA is mainly expressed in glandular cells of endometrium. (3) PAI-1 expression is linked to a specific population of trophoblasts that confront maternal cells, adding support to our view that it has a regulatory role in trophoblast invasion. (4) Localization of tPA antigen confirms that uterine glands are the major source of tPA and that it is also closely associated with fibrin(ogen) suggesting its possible function during implantation is fibrinolysis. (5) Unlike uPA mRNA, however, the distribution of uPA protein and its cell surface receptor uPAR suggests that it mediates trophoblast invasion and plays a significant role in angiogenesis. (6) PAI-2, the inhibitor associated with pregnancy in humans, was found in unidentified cells located specifically along the maternofetal junction. This localization adjacent to areas of cell death at the maternofetal junction implies that it may have a role as a protective curtain with anti-apoptotic function. In conclusion our results suggest that gene expression of PAs and PAIs in early implantation sites are tissue-specific, location-sensitive and function-related.