RAGE/NF-κB通路对妊娠期糖尿病大鼠胎盘滋养细胞凋亡及胎盘屏障功能改变的影响

目的:探讨晚期糖基化终末产物受体(RAGE)/核转录因子-κB(NF-κB)通路对妊娠期糖尿病(GDM)大鼠胎盘滋养细胞凋亡及胎盘屏障功能改变的影响。方法:将受孕雌性SD大鼠随机分为正常妊娠组、模型组(GDM组)、RAGE抑制剂组(FPS-ZM1组)、RAGE抑制剂阴性对照组(FPS-ZM1 NC组)、RAGE激活剂组(RAGE组)、RAGE激活剂阴性对照组(RAGE NC组),每组20只。除正常妊娠组外,其余各组均建立GDM模型,并在妊娠第5天开始给药,连续给药2周后,比较各组空腹血糖(FBG)、晚期糖基化终末产物(AGE)、胎盘重量、胎鼠重量、胎盘通透性、胎盘滋养细胞凋亡率;胎盘组织RAGE、NF-κB、紧密连接蛋白(TJ)、囊膜蛋白-2(Syncytin-2)、调解超家族蛋白2 A(MFSD2 A)、抗凋亡蛋白B淋巴细胞瘤-2(Bcl-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)表达水平的差异。结果:与正常妊娠组相比,GDM组大鼠FBG及AGE水平、胎盘重量及胎鼠重量、胎盘组织伊文思蓝(EB)含量、RAGE和NF-κB阳性表达水平、IL-6、TNF-α、Bcl...     

胎盘生长因子在妊娠期糖尿病患者胎盘中抑制滋养细胞凋亡的作用研究

目的:探讨胎盘生长因子(PLGF)对妊娠期糖尿病(GDM)患者胎盘滋养细胞凋亡的影响。方法:收集20例GDM和20例正常孕妇胎盘组织,采用HE染色法观察GDM患者胎盘组织形态学变化。TUNEL染色以及Caspase-3活性检测胎盘中细胞凋亡情况。Western blot检测胎盘中PLGF蛋白表达情况,免疫组化观察PLGF的原位表达。离体培养人绒毛滋养细胞(HTR-8/SVneo),分为对照组、高糖组(HG)、PLGF+高糖组(PLGF+HG)和PLGF组,应用流式细胞术检测各组HTR-8/SVneo滋养细胞的凋亡率。结果:与对照组相比,GDM患者胎盘中滋养细胞凋亡明显减少,Caspase-3活性明显减弱。PLGF在GDM胎盘中的表达明显高于对照组;高糖诱导HTR-8/SVneo滋养细胞凋亡增加,PLGF预处理明显逆转高糖诱导的HTR-8/SVneo滋养细胞凋亡增加。结论:GDM患者胎盘中滋养细胞凋亡明显减少,而胎盘中PLGF表达升高。离体实验进一步证明PLGF能够抑制高糖所致HTR-8/SVneo滋养细胞凋亡增加,因此PLGF表达升高可能是GDM患者胎盘中滋养细胞凋亡减少的原因。     

胎盘原位滋养细胞肿瘤

胎盘原位滋养细胞肿瘤浙江医科大学附属妇产科医院病例报告患者２７岁，已婚。因月经周期不规则伴经量减少３年，子宫增大半个月，于１９９５年４月３日入院。患者于１９９１年８月在当地医院足月自然分娩，经过顺利。产褥期恢复无明显异常。哺乳期１０个月。于产后８个月...     

胎盘部位滋养细胞肿瘤

<正> 1895年,Marchard发现一些不能归入常见类型滋养细胞肿瘤的病变,称之为不典型绒毛膜上皮癌(atypical chorioepithelioma)。嗣后,由于对这一病变认识不清,被冠以各种名称,如非特异性子宫肉瘤(nonspecific uterine sarcoma)、绒毛膜上皮增     

胎盘部位滋养细胞肿瘤的临床特点

1976年 Kurman 等描述了一种变异的滋养细胞疾病并称之为滋养细胞假瘤。在形态学上细胞类似滋养细胞并且侵入周围组织。对这些侵入的细胞进行免疫酶学研究提示存在有绒毛膜促性腺激素(hcG)。本病也有一些特点不同于绒癌。该肿瘤缺少通常如绒癌那样同时具有细胞滋养细胞及合体滋养细胞的两种细胞类型,在瘤体中亦无广泛坏死及出血。细胞浸润的特点是细胞潜入肌束及纤维束之间。在12例此种患者中,无因本病而     

胎盘部位滋养细胞肿瘤概况

胎盘部位滋养细胞肿瘤概况天津市第二中心医院（３００１２０）范女郎娣天津市红桥医院（３００１３１）王展宏本瘤早年曾被误称“合体细胞子宫内膜炎（ｓｙｎｃｙ－ｔｉａｌｅｎｄｏｍｅｔｒｉｔｉｓ）”，但其既非炎症亦非合体滋养细胞的增殖。Ｋｕｒｍａｎ（１９７６）...     

妊高征胎盘滋养细胞发育与细胞因子及基因调控

滋养细胞在妊娠高血压综合征(PIH)病因学中的作用日益引起重视。滋养细胞数目的改变，毒性作用，浸润能力的改变以及免疫学方面的异常在PIH的发生过程中起决定性作用。滋养细胞可合成多种细胞因子，其中很多因子与PIH的发生有密切的关系。胎盘中大量滋养细胞的凋亡可能影响PIH的发生和结局。对其深入研究对PIH的发生机制和临床治疗有重要意义。     

胎盘部位滋养细胞肿瘤临床研究进展

胎盘部位滋养细胞肿瘤(PSTT)是一种罕见的妊娠滋养细胞肿瘤，临床上一般表现为良性行为，但亦有部分出现复发和转移。PSTT的临床表现无特异性，诊断主要依靠病理学IT细胞较强的HPL染色阳性和肿瘤细胞特征性的超微结构改变。如何早期判断该病的良恶性及恶性PSTT的治疗方式和预后，引起较多关注，就PSTT临床研究进展作一综述。     

胎盘部位滋养细胞肿瘤诊治进展

<正>早在公元前400年希波克拉底报道了子宫浮肿,现在看来很有可能就是滋养细胞疾病。1976年Kurman和Scully首先定义了"滋养细胞肿瘤"(ges-     

胎盘部位滋养细胞肿瘤1例报告

1病历摘要患者38岁,孕3产1。主因人工流产术后两个月余,血HCG异常于2010-06-14入院。患者平素月经规律,停经40余天,行超声检查,提示宫内早孕,行人工流产术,诉术中刮出绒毛状组织少许,而后一直未来月经,人流术后2个月余,行超声检查提示子宫内异常回声区,伴低阻血流。     

The role of adipokines in the pathogenesis of gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not been completely clarified. Two major metabolic disorders, insulin resistance and β-cells dysfunction, play currently major role in pathogenesis of GDM. These elements are influenced by the amount of adipose tissue present before and/or during the pregnancy. Consequently, adipokines (adiponectin (APN), leptin (LPT), adipocyte fatty acid-binding protein, resistin, visfatin, omentin, vaspin, apelin, chemerin) secreted by adipose tissue, may contribute directly and/or indirectly, through the enhancement of chronic inflammation, aggravating insulin resistance and promoting GDM onset. This review aims to outline the potential physiopathological and prognostic role in GDM of adipokines, mainly APN and LPT.     

Incidence of gestational hypertension in gestational diabetes mellitus

The purpose of this study has been to establish the incidence of gestational hypertension (GH) in women with gestational diabetes mellitus (GDM) and to examine the frequency of complications in women with co-existent GDM and GH. Furthermore, we wished to evaluate the significance of urine albumin excretion determined by the urine albumin creatinine ratio (ACR). A total of 215 successive pregnancies with risk factors for gestational diabetes, as defined by the Danish National Board of Health screened for gestational diabetes by the WHO criteria, were reviewed. Women who had a normal OGTT during the screening served as controls. Gestational hypertension was defined as a mean arterial pressure (MAP) >105 mmHg (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg). The two groups were comparable with regard to initial body mass index (BMI) and MAP. GH appeared with a higher frequency in women with GDM (28%) than in women with normal OGTT (10%) P=0.003 χ² test. Serious complications (perinatal mortality, malformations, acute caesarean section) also appeared with a higher frequency in women with GH and GDM (10%) than in women with GH but with normal OGTT (2%) P=0.0083 χ² test. We observed a significant increase in ACR in the group with complications (GDM and GH) during gestation regardless of intensive antihypertensive treatment. We also observed that ACR was significantly higher in women with GDM and GH when compared to women with GDM and a normal blood pressure. The BMI was consistently higher in women with GH, regardless of whether they had GDM or not as compared to the normotensive group. GH appears with a higher frequency in women with GDM and the co-existence seems correlated with a higher frequency of complications. The correlation between urine albumin excretion and complications might suggest that regulating GH should strive to normalise ACR in women with GDM. Received: 25 October 2001 / Accepted: 8 December 2001 Correspondence to J. Kvetny     

母亲妊娠期糖尿病对胎儿和婴儿心功能的影响

目的 探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)母亲的子代婴儿期心脏解剖和功能的变化.方法 选择2007年1月至8月在复旦大学附属妇产科医院行产前检查并分娩的GDM孕妇18例为GDM组,选择同期24例孕周匹配的正常妊娠孕妇作为对照组,均在妊娠晚期接受胎儿超声心动图检查,测量胎儿心脏大小和功能各项指标,组间比较采用两独立样本t检验.GDM组 孕妇的子代于2～3月龄时接受小儿超声心动图随访,选择同期24例月龄匹配的正常妊娠的健康婴儿为对照组,再次评价和比较婴儿心脏大小和功能各项指标,组间差异比较采用方差分析及两两检验.结果 GDM组18例胎儿中出生6例大于胎龄儿(1arge for gestational age,LGA),占33.3%,12例(66.7%)适于胎龄儿(appropriate for gestational age,AGA);对照组24例胎儿中出生2例LGA(8.3%)和22例(91.7%)AGA(x2=3.840,P=0.05).GDM组胎儿的左室壁和室间隔收缩末期厚度大于对照组(P均＜0.05);至婴儿期室壁厚度未再增加,而LGA婴儿的左室壁收缩末期厚度[(4.55±0.37)mm]和左心室舒张末期长径[(37.3±2.3)mm]仍大于对照组[分别为(4.13±0.39)mm和(34.6±2.6)mm](P均＜0.05).GDM组胎儿的主、肺动脉峰速和左心输出量均大于对照组胎儿(P均＜0.01),右心/左心输出量值小于对照组(分别为1.198±0.206和1.430±0.321,t=-2.668,P=0.011);至婴儿期,GDM组仅AGA婴儿的右心/左心输出量值大于对照组(P＜0.05).GDM组胎儿左房缩短分数,三尖瓣E峰、A峰速度和E/A比值小于对照组(P均＜0.05);至婴儿期,GDM组仅左房缩短分数(0.356±0.040)仍小于对照组(0.386±0.041)(t=-2.332,P=0.025).GDM组胎儿的左、右心室Tei指数分别为0.482±0.129和0.414±0.094,均大于对照组(分别为0.309±0.074和0.283±0.072)(t分别=5.075和5.129,P均=0.000);至婴儿期,GDM组LGA和AGA婴儿的左、右心室 Tei指数均较胎儿期明显降低,并与对照组婴儿差异无统计学意义.结论 血糖控制良好的GDM母亲分娩的婴儿在2～3月龄时,心脏的解剖和功能指标均较胎儿期更接近健康婴儿.     

Inflammatory mediators in gestational diabetes mellitus

The connection between inflammation and insulin resistance has garnered much interest in the past decade. Epidemiologic as well as experimental data have supported the association. The purpose of this article is to review the current evidence linking inflammatory mediators and gestational diabetes mellitus.     

推进循证依据在妊娠期糖尿病诊治实践中的应用

随着健康与疾病的发育起源(Development of Health and Disease,DOHaD)学说研究的不断深入,孕期高血糖对胎儿近远期的影响越来越受到关注.尽管我国对妊娠期糖尿病(gestational diabetes mellitus,GDM)的研究仅有20余年历史,但该领域的相关研究已经取得一定进展,并受到国际同行的关注.     

Placental vanadium in gestational diabetes mellitus

Although many studies in animal models and in cell cultures have shown that vanadate has insulin-like effects, it has not been studied in human diabetes mellitus. In this study the levels of vanadium in human placentae from 23 pregnancies complicated by gestational diabetes mellitus were compared with 18 uncomplicated non-diabetic pregnancies closely matched for maternal age, gravidity, and gestational age. Using the unpaired Student's t-test, the mid-disc placental levels in gestational diabetes (7.62 +/- 1.29 micrograms/g dry weight) were significantly lower (p less than 0.05) than controls (8.73 +/- 1.85 micrograms/g dry weight). These findings appear to be independent of placental size and birthweight. When these data were analyzed according to treatment, the vanadium levels in insulin-treated cases (8.07 +/- 1.32 micrograms/g dry weight) were not significantly different from the matched controls (8.84 +/- 1.69 micrograms/dry weight); the levels in noninsulin treated cases (7.08 +/- 1.25 micrograms/g dry weight), however, were significantly (p less than 0.005) lower than controls (8.99 +/- 1.96 micrograms/g dry weight). It is interesting to speculate that there may be increased binding of vanadium to maternal tissues in human diabetes mellitus when insulin is deficient.     

Risk of diabetes mellitus after pregnancy complicated by gestational diabetes mellitus (GDM)

OBJECTIVES: The aim of the study was an assessment of glucose tolerance disorders' (GTD) prevalence after pregnancy complicated by GDM. DESIGN: Retro- and prospective clinical study. MATERIAL AND METHODS: The group of 461 women having GDM in their index pregnancies was invited to postpartum glucose metabolism assessment. Of them 192 subjects responded positively. In 47 of them the postpartum diagnosis of diabetes had already been established. The remaining 145 subjects underwent detailed testing that embraced fasting plasma glucose and whole blood HbA1c level measurement. Oral 75-g glucose tolerance test (OGTT) was also performed. RESULTS: OGTT revealed GTD in 55 subjects. Diabetes was found in 8 cases, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) in 23 and 24 cases respectively. Postpartum GTD appeared in 63.3% of insulin treated subjects (GDM2) compared with 30.1% of women treated with diet only (GDM1). A group with pathological OGTT had mean HbA1c concentration significantly higher compared to the one with normal test results (6.0+/-1.7% vs. 5.1+/-0.3%; p<0.001), although HbA1c>6.0% was observed only in 23.6% women with GTD. Moreover, in 25% of subject with newly diagnosed diabetes HbA1c level did not exceeded 6.0%. CONCLUSIONS: 1. More than 50% of subjects with GDM developed diabetes or other GTD during the first 6 years postpartum. 2. Risk of postpartum GTD is significantly higher in women treated with insulin during pregnancy. 3. HbA1c measurement is less sensitive than OGTT for detection of GTD after pregnancy complicated by GDM.     

自噬在妊娠期糖尿病中的作用

自噬广泛存在于机体细胞中,能够保护细胞,维持正常的细胞功能和组织结构。过度自噬会引起细胞死亡,导致组织出现病理性损伤。胎盘通过自噬维持正常生理功能。在妊娠期糖尿病孕妇的胎盘中,高血糖能够诱导滋养细胞过度自噬,抑制胎盘血管生成,导致组织缺血、缺氧及细胞活性氧水平升高,出现胎盘功能障碍,增加早产、巨大儿等不良妊娠结局的发生风险。     

Postpartum assessment of the beta cell function and insulin resistance for Chinese women with previous gestational diabetes mellitus

Gestational diabetes mellitus (GDM) imparts a high risk of developing postpartum diabetes and is considered to be an early stage of type 2 diabetes mellitus (T2DM). In this study, a 75-g oral glucose tolerance test was performed on 472 women with GDM at 6–8 weeks after delivery. The clinical and metabolic characteristics were compared between the patients with normal glucose tolerance (NGT) and abnormal glucose metabolism (AGM). These data were then compared between pre-diabetic and diabetic patients. A total of 37.7% of the women with GDM continued to have abnormal glucose levels after delivery. Compared with the women who reverted to normal, HOMA-IR was significantly higher in AGM. A multiple stepwise regression analysis revealed that age, the postpartum body mass index (BMI), low density lipoprotein-cholesterol (LDL-C), 2?h glucose load plasma glucose (2?h PG), triglycerides (TG), hemoglobin A1c (HbA1c), 1?h glucose load plasma insulin (INS) level, and 2?h INS level were independent risk factors for the development of insulin resistance after delivery. This study has identified a high prevalence of AGM after GDM. Insulin resistance appears to be the major contributor. Any treatment to reduce the postpartum BMI and lipids level may be beneficial to decrease insulin resistance.