胎盘生长因子抑制剂治疗子宫内膜异位症的实验研究

目的：初步探讨胎盘生长因子（ PLGF）抑制剂对大鼠子宫内膜异位症（ EMS）的影响。方法用EMS患者分泌期子宫内膜配成组织悬液接种于雌性严重联合免疫缺陷（ SCID）小鼠腹壁以建立EMS动物模型,按照病灶面积分成2组,每组16只,实验组给予PLGF单克隆抗体50mg· kg^-1· d^-1,腹腔注射,连续注射10d;对照组给予磷酸缓冲液20mL· kg^-1· d^-1腹腔注射,连续注射10d。结果实验组异位病灶面积小于对照组（t＝3．6,P＜0．05）,实验组病理学评分小于对照组（t＝16．2,P＜0．05）,实验组血管密度小于对照组（t＝16．4,P＜0．05）。结论 PLGF对血管生成有抑制作用,可以用来治疗大鼠子宫内膜异位症。     

Placenta growth factor promotes migration through regulating epithelial-mesenchymal transition-related protein expression in cervical cancer

Epithelial-mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis by enabling cancer cells to depart from the primary tumor, invade surrounding tissue and disseminate to distant organs. The existence and function of EMT in cervical cancer is poorly understood. Placental growth factor (PLGF) has been shown to associate with EMT in various cancers. However, whether PLGF is involved in EMT in cervical cancer remains unclear. Thus the present study examined the relationship between PLGF expression and EMT-related proteins in 110 cervical lesions samples. We detected that PLGF was expressed in 61.8% cervical lesion sections. In addition, PLGF expression is positively correlated with low expression level of E-cadherin and high expression level of vimentin. Serum samples and cervical lavage samples were collected from patients with pre-invasive and invasive lesion of uterine cervix or normal control group, the PLGF levels were determined by enzyme-linked immunosorbent assay (ELISA). We found that a significantly high level of PLGF could be detected both in serum and vaginal lavage compared with normal women group, and there is no significant difference between serum and lavage in PLGF level. In addition, whatever in lavage or in serum, the PLGF level in stage I and II was significantly higher than it in CINIII or cancer in situ. However, there is no significant difference between the stage I and stage II; we also found that exogenous PLGF promotes molecular changes of epithelial-mesenchymal transition (EMT) in siha cells. In addition, application of a specific EKR1/2 inhibitor could reverse the effects of PLGF. These findings suggested that PLGF could regulate the expression of EMT-related proteins and promote migration of siha cells through ERK/MAPK signaling pathway. Therapies that targets PLGF/Flt-1/ERK/MAPK signaling pathway may be beneficial in treatment of cervical cancer.     

血清sFlt-1､PLGF水平及比值变化预测孕妇轻度子痫前期发病的Meta分析

目的:探讨血清可溶性血管内皮生长因子受体-1(soluble fms-like tyrosine kinase-1,sFlt-1)?胎盘生长因子(placental growth factor,PLGF)水平及比值变化与轻度子痫前期发病关系?方法:检索万方?CNKI?PubMed?Embase和Cochrane收集1994—2016年国内外公开发表的关于血清sFlt-1?PLGF水平及比值变化与轻度子痫前期关系的中英文病例对照研究,剔除不符合标准的文献,对纳入的文章采用Review Manager 5.3软件对结果进行统计分析?结果:共纳入文献17篇,其中中文文献14篇,英文文献3篇?血清sFlt-1表达水平与轻度子痫前期的关系的异质性检验I 2 = 96%,P < 0.000 01,存在明显的异质性,合并效应SMD=4.89(95%CI:3.60~6.17),P < 0.000 01,差异有统计学意义?血清PLGF表达水平与轻度子痫前期的关系的异质性检验I 2 = 93%,P < 0.000 01,存在明显的异质性,合并效应SMD=-2.32(95%CI:-2.91~-1.72),P < 0.000 01,差异有统计学意义?轻度子痫前期组和正常对照组血清sFlt-1/PLGF比值异质性检验I 2 = 98%,P < 0.000 01,合并效应SMD=1.95(95%CI:0.50~3.40),P < 0.000 01,差异有统计学意义?结论:PLGF与轻度子痫前期的发病具有密切关系,血清sFlt-1的表达水平与轻度子痫前期有关,sFlt-1以及sFlt-1/PLGF比值可以作为辅助诊断轻度子痫前期的有效指标     

胎盘生长因子抗体对大鼠子宫内膜异位症模型的治疗作用

目的 探讨胎盘生长因子抗体(anti-PLGF)对大鼠子宫内膜异位症模型的治疗作用.方法 自体移植法建立大鼠子宫内膜异位症模型,分别观察anti-PLGF对大鼠子宫内膜异位症模型异位子宫内膜形态结构、腹腔液血管内皮生长因子和白细胞介素-8的影响.结果 anti-PLGF 1 mg/kg剂量组能明显抑制模型大鼠腹腔液中血管内皮生长因子水平,并能显著减小大鼠子宫内膜异位组织的体积,与模型组比较差异有统计学意义(P＜0.05),而腹腔液中白细胞介素-8水平无明显变化.结论 anti-PLGF通过抑制异位内膜的血管形成,从而有效抑制异位内膜的生长.     

胎儿生长受限大鼠胎盘sFLT-1、PLGF的表达及川芎嗪的干预作用

目的：观察川芎嗪干预下大鼠胎儿生长受限（FGR）胎盘中可溶性血管内皮生长因子受体-1（SFLT-1）、胎盘生长因子（PLGF）的表达及其意义。方法：15只SD大鼠分为川芎嗪（TMP）组（FGR治疗组）、FGR非治疗组、正常对照组,FGR治疗组给予高粱酒灌胃,烟熏3次,每次15min,第13天起每天清晨烟熏灌胃后给予TMP 8mg/kg腹腔注射;FGR非治疗组从妊娠第7天起,每日给予高粱酒灌胃,烟熏3次,每次15min;正常对照组从妊娠第7天起,每天9点9mL/kg生理盐水灌胃,每天3次烟熏箱关15min但不烟熏。3组大鼠均于妊娠第20天解剖,比较各组大鼠胎盘PLGF、sFLt-1的表达。结果：FGR治疗组与FGR非治疗组、正常对照组SFLT-1差异无统计学意义（P〉0.05）;FGR治疗组与FGR非治疗组、正常对照组PLGF差异有统计学意义（P〈0.01）。结论：FGR大鼠胎盘SFLT-1升高、PLGF下降,SFLT-1、PLGF可考虑作为胎儿生长受限的筛查指标;经川芎嗪处理后的大鼠胎盘SFLT-1无显著差异,PLGF升高,川芎嗪可考虑作为胎儿生长受限的治疗药物。     

胎盘生长因子作为预测子痫前期标记物的研究

目的检测正常妊娠与妊娠期高血压疾病患者不同孕周的血清胎盘生长因子（PLGF）水平，探讨母血PLGF水平是否可作为预测孕妇发生子痫前期的标记物。方法采用酶联免疫吸附法（ELISA）检测215例孕妇不同孕周的血清PLGF水平．其中正常妊娠组197例，妊娠期高血压疾病组18例。结果PLGF均呈峰形分泌，正常妊娠组在早孕期、孕20周、孕30周、孕40周时PLGF的均值分别为53．28pg／ml、323．63pg／ml、596．78pg／ml、467．42pg／ml，轻度子痫前期组为27。38pg／ml、183．58pg／ml、301．28pg／ml、276．44pg／ml，重度子痫前期组为22．52pg,／ml、95．72pg／ml、217．92pg／ml、148．56pg／ml，轻度与重度组PLGF水平均显著低于正常妊娠组水平（P〈0．01），并且随着PI．GF水平的降低，妊娠期高血压疾病的病情亦逐渐加重．．在孕早期PLGF≤32pg／ml时，预测子痫前期的敏感性为87．5％，特异性97．6％。在孕20周PLGF≤240pg／ml时，敏感性为75．0％，特异性为94．2％。结论PLGF对胎盘血管的形戍有重要调节作用，PLGF的下降与妊娠期高血压疾病的发病相关。且PLGF的下降早于临床出现子痫前期的症状，可以作为预测子痫前期的一种标记物。     

稽留流产绒毛中HIF-1α、VEGF和PLGF的表达及意义

目的:检测缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)及胎盘生长因子(PLGF)在稽留流产(MA)绒毛组织中的表达,探讨3种因子在维持正常妊娠中的作用.方法:选取昆明市第一人民医院产科收治的MA患者36例(研究组)及行人工流产的正常早孕妇女28例(对照组).应用免疫组化法检测两组绒毛组织中HIF-1α、VEGF和PLGF的表达.结果:研究组绒毛水肿,细胞滋养细胞增生、数量增加,合体滋养细胞明显减少,甚至断裂消失.HIF-1 α、VEGF、PLGF在两组妇女绒毛滋养细胞的胞浆均有表达,但研究组HIF-1α、VEGF、PLGF的阳性表达率均低于对照组(16.67 vs 57.14％,66.67％ vs 100.00％,77.78％ vs 100.00％,P＜0.05).结论:HIF-1a、VEGF和PLGF与正常妊娠的维持有关,其表达异常可能导致MA.     

Immunomodulation and preeclampsia

Preeclampsia (PE) is an enigmatic syndrome, still with unknown aetiology and multi-factorial pathogenesis. Our understanding of the role of the immune system in PE development has undergone a transformation over the years. From a model based on the alterations in cell-mediated immunity, research moved on to a vision centred on the alteration of the humoural immunity and on the systemic involvement of the inflammatory system. The first hypothesis was classically derived from the evidence that an adequate maternal immunological response is necessary in pregnancy to allow the survival of the foetus. An abnormal response of the maternal immune system against the placenta may be the first pathogenetic step of PE, followed by a systemic inflammatory reaction. Currently available treatments for PE are mainly preventative with aspirin. Treatment aims to modulate inflammation and the immune system before their changes become established.