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浙江大学学报（医学版） 2008年第3期37卷 226-232页

作者：王秀敏梁黎杜立中傅君芬浙江大学医学院附属儿童医院内分泌科浙江杭州310003

目的:探讨宫内生长迟缓大鼠胰岛ghrelin表达规律,阐明ghrelin是否参与宫内生长迟缓所致的胰岛素抵抗的进程。方法:建立宫内生长迟缓(I组)和正常出生体重(N组)大鼠模型;测定血糖、血ghrelin、血胰岛素水平、胰腺ghrelin含量和高糖刺激后... 详细信息

目的:探讨宫内生长迟缓大鼠胰岛ghrelin表达规律,阐明ghrelin是否参与宫内生长迟缓所致的胰岛素抵抗的进程。方法:建立宫内生长迟缓(I组)和正常出生体重(N组)大鼠模型;测定血糖、血ghrelin、血胰岛素水平、胰腺ghrelin含量和高糖刺激后胰腺胰岛素分泌量;RT-PCR检测胰腺ghrelin和胰岛素mRNA水平;免疫荧光和共聚焦技术检测胰岛ghrelin和胰岛素的阳性细胞数。结果:I组1 d、3 d和7 d的血浆胰岛素水平均低于N组(P<0.05),胰岛素抵抗指数(HOMA-IR)也低于N组相应时间点(P<0.05)。两组血糖、血浆胰岛素、HOMA-IR和血浆ghrelin水平有随时间变化的趋势(F=4.12~125.97,P均<0.001)。I组血浆ghrelin水平与HOMA-IR呈正相关(r=0.553,P=0.000)。两组胰腺ghrelin含量、ghrelin mRNA、insulin+细胞和ghrelin+细胞比例均随日龄增长呈下降趋势(F=-49.29~427.28,P均<0.001),两组间ghrelin含量和mRNA变化差异显著(F=-69.98~169.22,P均<0.05);I组和N组胰岛素分泌水平分别与其胰腺ghrelin含量呈负相关(r=-0.895,P=0.000;r=-0.458,P=0.002),胰岛ghrelin+细胞比例分别与其胰腺insulin+细胞比例呈负相关(r=-0.810,P=0.000;r=-0.714,P=0.000)。两组大鼠胰岛ghrelin+细胞分布不同。结论:宫内生长迟缓对血浆ghrelin水平、胰岛素分泌的影响在生后持续存在,ghrelin参与了宫内生长迟缓者发生胰岛素抵抗的进程。

关键词：胎儿生长迟缓/病理生理学胰岛素抗药性血糖/代谢胰岛素/代谢肽类

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不同出生体重新生大鼠胰腺ghrelin和钙通道表达的研究

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浙江大学学报（医学版） 2008年第3期37卷 233-239页

作者：许燕萍梁黎王秀敏吴亦栋顾伟忠浙江大学医学院附属儿童医院浙江杭州310003

目的:探讨宫内营养环境对大鼠胰腺ghrelin和胰岛细胞团上L型钙通道(Cav1.2、Cav1.3)相对丰度的影响。方法:建立不同出生体重新生大鼠模型,分别取新生第1天大鼠胰腺或分离的胰岛细胞团组织,用实时荧光定量RT-PCR观察不同出生体重组胰腺gh... 详细信息

目的:探讨宫内营养环境对大鼠胰腺ghrelin和胰岛细胞团上L型钙通道(Cav1.2、Cav1.3)相对丰度的影响。方法:建立不同出生体重新生大鼠模型,分别取新生第1天大鼠胰腺或分离的胰岛细胞团组织,用实时荧光定量RT-PCR观察不同出生体重组胰腺ghrelin mRNA表达的变化和胰岛细胞团上Cav1.2、Cav1.3 mRNA的差异;同时,对胰岛细胞团上ghrelin、Cav1.2、Cav1.3蛋白进行免疫组织化学染色。结果:实时荧光定量RT-PCR显示:新生大鼠小于胎龄儿(SGA)组胰腺ghrelin mRNA水平高于适于胎龄儿(AGA)组的表达(P<0.05)。胰岛细胞团上Cav1.2 mRNA SGA组和大于胎龄儿(LGA)组表达量均小于AGA组,Cav1.3 mRNA SGA组小于AGA组(P<0.05)。免疫组化积分光密度数据显示与实时荧光定量RT-PCR结果呈相同趋势。结论:早期宫内营养状况过剩或缺乏可能导致胰腺分化和成熟障碍,并引起胰岛细胞团上ghrelin和钙通道表达差异。

关键词：胎儿生长迟缓/病理生理学肽类钙通道 L型胰岛/细胞学婴儿小于胎龄聚合酶链反应免疫组织化学

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从宫内发育研究代谢综合征的发病机制

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浙江大学学报（医学版） 2008年第3期37卷 221-225页

作者：梁黎何梦藻浙江大学医学院附属儿童医院内分泌科浙江杭州310003

宫内发育迟缓与成年后代谢综合征(metabolic syndrome,MS)关系密切。研究发现,宫内营养不良可通过影响胎儿胰岛β细胞的发育和功能、干扰胎儿的糖脂代谢、调节激素水平、调控基因的修饰与表达等多种途径影响胎儿的生长发育与物质代谢,... 详细信息

宫内发育迟缓与成年后代谢综合征(metabolic syndrome,MS)关系密切。研究发现,宫内营养不良可通过影响胎儿胰岛β细胞的发育和功能、干扰胎儿的糖脂代谢、调节激素水平、调控基因的修饰与表达等多种途径影响胎儿的生长发育与物质代谢,对生后MS的发病起着重要的推动作用。

关键词：代谢综合征胎儿生长迟缓/病理生理学胰岛/胚胎学血糖/代谢脂类/代谢

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Doppler fetal circulation in pregnancies complicated by pre-eclampsia or delivery of a small for gestational age baby: 2. Longitudinal analysis

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BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY 1999年第5期106卷 453-466页

作者： Harrington, K Thompson, MO Carpenter, RG Nguyen, M Campbell, S Homerton Hosp Acad Dept Obstet & Gynaecol London E9 6SR England London Sch Hyg & Trop Med Dept Med Stat London WC1 England Univ London St Georges Hosp London England

Objective To observe the longitudinal changes in growth, and associated Doppler measurements, of the fetal circulation in pregnancies with a normal outcome and those complicated by pre-eclampsia, birth of a small for gestational age baby, or a combination of these complications. Methods Two hundred and ninety-two women had serial ultrasound scans performed from the 24th week of pregnancy. Measurements obtained included: the abdominal circumference, umbilical artery pulsatility index, the middle cerebral artery pulsatility index and time-averaged velocity, and the thoracic aorta pulsatility index and time-averaged velocity. Outcome measures included the birth of a small for gestational age infant, pre-eclampsia or a combination of these complications. Results One hundred and sixty-seven pregnancies ended in the normal birth of an appropriately grown infant at term, while 105 had a complicated outcome. They were divided into three categories: preeclampsia only (i.e. with the birth of an appropriately grown fetus, n = 13);small for gestational age only with no evidence of pre-eclampsia, n = 55;and pre-eclampsia complicated by the birth of a small for gestational age infant, n = 37. The group with pre-eclampsia complicated by small for gestational age was closest in characteristics to true clinical intrauterine growth restriction. A reduction in the abdominal circumference mirrored a rise in the umbilical artery pulsatility index and preceded changes in the middle cerebral artery and thoracic aorta. The greatest degree of change in the fetal circulation was observed during the three weeks preceding delivery. Ratios of the values obtained from the fetal and umbilical circulation demonstrated the greatest deviation from normal. Conclusions A reduction in fetal growth velocity preceded changes observed in the fetal circulation. Ratios of the fetal Doppler parameters provided the dearest evidence of deterioration in the fetal condition. The information provided may be of us

关键词：胎儿生长迟缓/病因学胎儿生长迟缓/病理生理学胎儿/血液供给婴儿小于胎龄纵向研究先兆子痫/并发症先兆子痫/病理生理学妊娠结局时间因素超声检查多普勒超声检查产前女(雌)性人类婴儿新生妊娠

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Internal jugular vein blood flow in normal and growth-restricted fetuses

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OBSTETRICS AND GYNECOLOGY 2000年第2期96卷 167-171页

作者： Weiner, Z Goldberg, Y Shalev, E Haemek Med Ctr Dept Obstet & Gynecol IL-18101 Afula Israel

Objective: To assess internal jugular vein blood now patterns during the second half of pregnancy in normal and growth-restricted fetuses. Methods: We did Doppler ultrasound studies of internal jugular veins and the inferior vena cavas longitudinally on 21 normal singleton fetuses from 20 weeks to term, and on eight growth-restricted fetuses with absent end-diastolic flow at the umbilical artery (UA). The three components of the venous flow velocity waveforms were used to calculate peak velocity ratio: Peak systolic velocity (S wave) minus reverse peak velocity (R wave) divided by peak velocity during early diastole (D wave) and velocity time integral ratio: systolic velocity time integral minus reverse velocity time integral divided by velocity time integral during early diastole. Statistical analysis of longitudinal measurements used K-related samples Friedman test;groups were compared with Mann-Whitney U test and chi(2) test. Results: In normal fetuses we found significant increases in peak velocity ratio and velocity time integral ratio of internal jugular veins and the inferior vena cavas throughout gestation. The mean +/- standard deviation (SD) of the internal jugular veins peak velocity ratio (1.12 +/- 0.4 versus 1.46 +/- 0.15, P < .05) and velocity time integral ratio (1.1 +/- 0.2 versus 1.55 +/- 0.17, P < .05) were significantly lower in growth-restricted fetuses compared with normal fetuses at 28-32 weeks' gestation but inferior vena cava indices were not. None of the eight growth-restricted fetuses had umbilical venous pulsations or changes in inferior vena cava or ductus venosus blood flow patterns. All had arterial pH above 7.15 at birth. Conclusion: Growth-restricted fetuses with absent end-diastolic velocity in the UA have changes in internal jugular vein blood flow patterns that probably indicate increased cerebral blood flow, more evidence of redistribution of blood flow in growth-restricted fetuses that can be used to maintain them. (C) 2000 by Th

关键词：脑/血液供给脑/胚胎学心舒期胎儿生长迟缓/诊断显像胎儿生长迟缓/病理生理学胎儿/血液供给孕龄颈静脉/诊断显像颈静脉/胚胎学颈静脉/生理学妊娠中期妊娠末期搏动血流局部血流超声检查多普勒超声检查产前成年人女(雌)性人类妊娠

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Restriction of placental and fetal growth in sheep alters fetal blood pressure responses to angiotensin II and captopril

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JOURNAL OF PHYSIOLOGY-LONDON 1999年第3期515卷 897-904页

作者： Edwards, LJ Simonetta, G Owens, JA Robinson, JS McMillen, IC Univ Adelaide Dept Physiol Adelaide SA 5005 Australia Univ Adelaide Dept Obstet & Gynecol Adelaide SA 5005 Australia

1. We have measured arterial blood pressure between 115 and 145 days gestation in normally grown fetal sheep (control group;n = 16) and in fetal sheep in which growth was restricted by experimental restriction of placental growth and development (PR group;n = 13). There was no significant difference in the mean gestational arterial blood pressure between the PR (42.7 +/- 2.6 mmHg) and control groups (37.7 +/- 2.3 mmHg). Mean arterial blood pressure and arterial P-O2 were significantly correlated in control animals (r = 0.53, P < 0.05, n = 16), but not in the PR, group. 2. There were no changes in mean arterial blood pressure in either the PR or control groups in response to captopril (7.5 mu g captopril min(-1);PR group n = 7, control group n = 6) between 115 and 125 days gestation. After 135 days gestation, there was a significant decrease (P < 0.05) in the fetal arterial blood pressure in the PR group but not in the control group during the captopril infusion (15 mu g captopril min(-1);PR group n = 7, control group n = 6). 3. There was a significant effect (F = 14.75;P < 0.001) of increasing doses of angiotensin II on fetal diastolic blood pressure in the PR and control groups. The effects of angiotensin II n ere different (F = 8.67;P < 0.05) in the PR and control groups at both gestational age ranges. 4. These data indicate that arterial blood pressure may be maintained by different mechanisms in growth restricted fetuses and normally grown counterparts and suggests a role for the fetal renin-angiotensin system in the maintenance of blood pressure in growth restricted fetuses.

关键词：血管紧张素Ⅱ/药理学血压/药物作用血压/生理学卡托普利/药理学心舒期胚胎和胎儿发育/生理学胎儿生长迟缓/病理生理学胎儿心脏/药物作用胎儿心脏/生理学胎儿心脏/病理生理学孕龄氧/血液胎盘/生理学绵羊心缩期动物女(雌)性妊娠

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Human trophoblast invasion and spiral artery transformation - The role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction

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AMERICAN JOURNAL OF PATHOLOGY 2001年第5期158卷 1713-1721页

作者： Lyall, F Bulmer, JN Duffie, E Cousins, F Theriault, A Robson, SC Duncan Guthrie Inst Med Genet Maternal & Fetal Med Sect Glasgow G3 8SJ Lanark Scotland Royal Victoria Infirm Dept Pathol Newcastle Upon Tyne NE1 4LP Tyne & Wear England Royal Victoria Infirm Dept Obstet & Gynaecol Newcastle Upon Tyne NE1 4LP Tyne & Wear England

During early human pregnancy extravillous cytotrophoblasts invade the uterus and spiral arteries transforming them into large vessels of low resistance, Failure of trophoblast invasion and spiral artery transformation occurs in preeclampsia and fetal growth restriction (FGR);these processes are not well understood. Recent studies have suggested that cytotrophoblasts that invade spiral arteries mimic the endothelial cells they replace and express PECAM-1. It was also reported that in preeclampsia, cytotrophoblasts fail to express PECAM-1 and that failure to express endothelial cell adhesion molecules may account for failed trophoblast invasion. Despite the possible importance of adhesion molecules in trophoblast invasion, no study has systematically investigated the expression of PECAM-1 in the placental bed throughout the period of invasion, particularly in the myometrial segments where the key failure occurs. There are no studies on PECAM-1 expression in the placental bed in FGR, We have examined the expression of PECAM-1 in placental bed biopsies and placentas from 8 to 19 weeks Of gestation and in the placenta and placental bed in the third trimester in cases of preeclampsia, FGR, and control pregnancies. PECAM-1 was expressed on endothelium of vessels in the placenta and placental bed but not by villous or extravillous trophoblasts in normal or pathological samples. These findings do not support a role for PECAM-1 in normal invasion or in the pathophysiology of preeclampsia or FGR.

关键词：抗原 CD31/分析抗原 CD31/生理学胎儿生长迟缓/病理生理学免疫组织化学胎盘/血液供给胎盘/化学先兆子痫/病理生理学妊娠初期妊娠中期妊娠末期滋养层/细胞学滋养层/生理学成年人女(雌)性人类妊娠

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Absent umbilical artery end-diastolic velocity in growth-restricted fetuses: A risk factor for neonatal thrombocytopenia

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OBSTETRICS AND GYNECOLOGY 2000年第2期96卷 162-166页

作者： Baschat, AA Gembruch, U Reiss, I Gortner, L Weiner, CP Harman, CR Univ Maryland Dept Obstet Gynecol & Reprod Sci Baltimore MD 21201 USA Med Univ Lubeck Dept Obstet D-23538 Lubeck Germany Med Univ Lubeck Dept Gynecol D-23538 Lubeck Germany Med Univ Lubeck Dept Pediat D-23538 Lubeck Germany

Objective: To examine the relationship between umbilical artery (UA) end-diastolic now and neonatal thrombocytopenia. Methods: We prospectively examined 115 anatomically normal single fetuses with UA pulsatility indices more than two standard deviations above the gestational age mean and subsequent birth weights below the tenth percentile. Peripheral neonatal platelet counts in fetuses with positive UA end-diastolic velocity were compared with those of fetuses with absent or reversed UA end-diastolic velocity. Results: Sixty-seven fetuses (58.3%) had positive UA end-diastolic velocity and 48 (41.7%) had absent or reversed UA end-diastolic velocity. Three neonates in the positive-dow group and 22 neonates in the absent- or reversed-flow group had platelet counts of less than 100,000/mm(3) (relative risk 10.2;95% confidence interval;3.2, 32.3;P < .001). Absent or reversed end-diastolic velocity had a sensitivity of 88%, specificity of 71%, positive predictive value of 46%, and negative predictive value of 96% for predicting neonatal thrombocytopenia. Neonates with absent or reversed flow also had lower median platelet counts (101,500/mm(3) versus 208,000/mm(3), P < .001), hemoglobin levels (15.1 versus 16.4 g/dL, P < .01), and hematocrits (47.6 versus 51.1%, P < .05), as well as higher nucleated red blood cell counts (191 versus 15 per 100 white blood cells, P < .001). Conclusion: Absent or reversed UA end-diastolic velocity in growth-restricted fetuses is associated with a statistically significant increase in risk of neonatal thrombocytopenia. (C) 2000 by The American College of Obstetricians and Gynecologists.

关键词：血流速度心舒期胎儿生长迟缓/诊断显像胎儿生长迟缓/病理生理学线性模型血小板计数试验预期值妊娠末期前瞻性研究搏动血流危险因素血小板减少/诊断超声检查多普勒/标准超声检查产前/标准脐动脉/诊断显像脐动脉/胚胎学脐动脉/生理学青少年成年人女(雌)性人类婴儿新生中年人妊娠

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不同出生体重新生大鼠胰腺ghrelin和钙通道表达的研究

不同出生体重新生大鼠胰腺ghrelin和钙通道表达的研究

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2008年浙江省儿科学学术年会

作者：许燕萍梁黎王秀敏吴亦栋顾伟忠浙江大学医学院附属儿童医院

目的:探讨宫内营养环境对大鼠胰腺ghrelin和胰岛细胞团上L型钙通道(Cav1.2、Cav1.3)相对丰度的影响。方法:建立不同出生体重新生大鼠模型,分别取新生第1天大鼠胰腺或分离的胰岛细胞团组织,用实时荧光定量RT-PCR观察不同出生体重组胰腺ghrelin mRNA表达的变化和胰岛细胞团上Car1.2、Cav1.3 mRNA的差异;同时对胰岛细胞团上ghrelin、Cav1.2、Cav1.3蛋白进行免疫

关键词：胎儿生长迟缓/病理生理学肽类(Peptides) 钙通道,L型胰岛/细胞学婴儿,小于胎龄聚合酶链反应免疫组织化学

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宫内生长迟缓大鼠胰腺ghrelin和胰岛素表达变化

宫内生长迟缓大鼠胰腺ghrelin和胰岛素表达变化

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2008年浙江省儿科学学术年会

作者：王秀敏梁黎杜立中傅君芬浙江大学医学院附属儿童医院内分泌科

目的:探讨宫内生长迟缓大鼠胰岛ghrelin表达规律,阐明ghrelin是否参与宫内生长迟缓所致的胰岛素抵抗的进程。方法:建立宫内生长迟缓(Ⅰ组)和正常出生体重(N组)大鼠模型;测定血糖、血ghrelin、血胰岛素水平、胰腺ghrelin含量和高糖刺激... 详细信息

目的:探讨宫内生长迟缓大鼠胰岛ghrelin表达规律,阐明ghrelin是否参与宫内生长迟缓所致的胰岛素抵抗的进程。方法:建立宫内生长迟缓(Ⅰ组)和正常出生体重(N组)大鼠模型;测定血糖、血ghrelin、血胰岛素水平、胰腺ghrelin含量和高糖刺激后胰腺胰岛素分泌量;RT-PCR检测胰腺ghrelin和胰岛素mRNA水平;免疫荧光和共聚焦技术检测胰岛ghrelin和胰岛素的阳性细胞数。采用重复

关键词：胎儿生长迟缓/病理生理学胰岛素抗药性血糖/代谢胰岛素/代谢肽类

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