早期营养干预对宫内生长迟缓大鼠瘦素、胰岛素敏感性的影响

目的　探寻既能保证宫内生长迟缓 (IUGR )大鼠生长追赶又可避免或减轻其在成年期产生胰岛素抵抗 (IR)的早期营养干预措施。方法　用孕鼠全程饥饿法建立IUGR大鼠模型。IUGR新生雌鼠60只随机分为五组 :( 1)IUGR对照组给予常规饲料 ;( 2 )高碳水化合物组 ;( 3 )高脂肪组 ;( 4 )高蛋白质组 ;( 5 )低蛋白质组。正常新生雌鼠 12只为正常对照组。幼鼠在 3周喂乳期间母鼠分别摄食上述饲料 ,第 4周起各组幼鼠均以常规饲料饲养。各组新生鼠于第 4周、12周分别测定体重、肾周脂肪重量、血清瘦素、血糖、胰岛素并计算胰岛素敏感指数 (ISI)。结果　IUGR高蛋白质组在 4周呈现不伴肾周脂肪增加的体重追赶生长 ,在 12周肾周脂肪不增多 ,瘦素、ISI均与正常对照组比较差异无显著性 ,不出现IR。结论　生后哺乳期高蛋白饮食继后恢复正常饮食是早期营养干预IUGR的合理措施。 12周时血清瘦素水平可作为观察IUGR大鼠成年后发生IR的一个生化指标。     

脐带血瘦素水平与胎儿宫内生长发育的关系

目的探讨瘦素在胎儿宫内生长发育中的作用,为代谢疾病的早期干预提供实验依据。方法连续入选2009年7月至2010年1月在北京协和医院出生的单胎足月新生儿266名（男婴140名,女婴126名）,留取脐带血,出生后立即测量新生儿体重、身长、头围及胎盘重量。根据出生体重将新生儿分为低出生体重组（n=58,男婴25例,女婴33例）、正常出生体重组（n=180,男婴99名,女婴81名）和高出生体重组（n：28,男婴16例,女婴12例）。采用放射免疫分析法测定脐带血瘦素水平。采用独立样本t检验、Pearson相关分析、多元线性回归分析进行数据统计。结果与正常出生体重组[（9±5）μg/L]相比,低出生体重组脐带血瘦素水平[（7±5）μg/L]明显降低（t=3．216,P〈0．05）,高出生体重组[（15±7）μg／L]明显升高（t=-4．026,P〈0．01）。女婴脐带血瘦素水平[（11±6）μg/L]明显高于男婴[（8±5）μg／L,t=一3．800,P〈0．01]。Pearson相关分析显示,脐带血瘦素水平与新生儿出生体重、身长、体质指数和胎盘重量呈显著正相关（r值分别为0．391、0．280、0．361、0．323,均P〈0．01）。校正母亲年龄、妊娠前体质指数、新生儿性别和胎龄后,脐带血瘦素水平仍与出生体重呈直线正相关（r2=0．289,P〈0．01）。结论脐带血瘦素水平与新生儿出生体重呈正相关,有望作为反映新生儿宫内生长发育的一个客观指标。     

宫内发育迟缓与胰岛素样生长因子及其结合蛋白关系的研究

为探讨宫内发育迟缓（IUGR）的发生机制,检测了86例新生儿脐血胰岛素样生长因子－1（IGF－1）、胰岛素样生长因子结合蛋白－3（IGFBP－3）水平,并分析上述指标变化与胎儿期生长的关系。将86例新生儿分为两组,IUGR（即小于胎龄儿）组22例,适于胎龄儿（AGA）组64例,采用竞争性放射免疫分析法（RIA）测定两组脐血IGF－1水平,非竞争性免疫放射分析法（IRMA）测定IGFBP－3水平。结果显示,与AGA组相比,IUGR组脐血IGF－1和IGFBP－3水平显著降低（P＜0．001）;IGF－1水平随胎龄及出生体重增加而增加（P＜0．01）;IGFBP－3水平与胎龄及出生体重呈相关（P＜0．01）;IGF－1与IGFBP－3呈正相关（P＜0．01）。认为IUGR与IGF－1及其结合蛋白密切相关,不论何种原因引起的IUGR,其脐血IGF－1、IGFBP－3水平均低,IGF－1水平下降与IGFBP－3下降相伴随;脐血IGF－1、IGFBP－3水平与胎龄及出生体重呈正相关,随着胎龄的增加和出生体重的增长,IGF－1、IGFBP－3水平不断升高。     

Increased human placental growth hormone at midtrimester pregnancies may be an index of intrauterine growth retardation related to preeclampsia

OBJECTIVE: To evaluate the relationship between maternal serum and amniotic fluid levels of human Placental Growth Hormone (hPGH) with the fetal intrauterine growth retardation (IUGR) related to preeclampsia. DESIGN: We analyzed samples in pairs of serum and amniotic fluid retrospectively from 25 women, who manifested preeclampsia and IUGR in the late second or the third trimester of gestation. The samples were obtained at 16-22 weeks' gestation during amniocentesis for fetal karyotyping. At this time, there was no clinical or sonographic evidence of preeclampsia or IUGR, respectively. Sixty-two serum samples were used as controls which were obtained at 16-22 weeks' gestation from women with singleton, uncomplicated pregnancies, with normal outcome, and appropriate for gestational age neonatal birth weight. Forty-seven amniotic fluid samples were also used as controls which were obtained at 16-22 weeks' gestation from the women that were included in the control group who underwent an amniocentesis. hPGH levels were measured by a solid phase immunoradiometric assay. RESULTS: The mean hPGH values in the serum and the amniotic fluid of the IUGR related to preeclampsia affected pregnancies were significantly higher (P<0.05) than those of the normal pregnancies at 16-22 weeks' gestation: mean+/-SD in the serum was 13.16+/-10.52 ng/ml vs. 4.39+/-2.23 ng/ml; mean+/-SD in the amniotic fluid 2.49+/-1.6 ng/ml vs. 0.82+/-0.67 ng/ml. CONCLUSION: hPGH levels in maternal serum and amniotic fluid were found to be higher at 16-22 weeks' gestation in pregnancies that will be complicated subsequently by IUGR related to preeclampsia. Our findings suggest that the evaluation of the changes of hPGH levels at midtrimester should be further investigated for the possibility to provide a potential predictive index of IUGR and preeclampsia.     

宫内发育迟缓大鼠不同阶段胰岛功能及胰岛素敏感性的研究

采用营养不良法建立官内发育迟缓(intrauterine growth retardation,IUGR)大鼠模型,发现IUGR大鼠胰腺发育受损、胰岛β细胞功能减退,随年龄增长逐渐出现糖耐量受损及胰岛素敏感性下降.     

宫内发育迟缓大鼠第36周胰岛素合成相关基因的表达

目的研究宫内发育迟缓（IUGR）大鼠第36周胰腺组织中胰岛素合成相关基因表达的变化。方法将20只体重250-270g的8-10周健康雌性SD大鼠,饲养于无特定病原体（SPF）级动物房,适应性饲养2周后将雌雄鼠合笼,以发现阴栓当天记为雌鼠受孕第1天,雌鼠受孕后随机数字表法分为造模组（n=10）和对照组（n=10）。采用孕中晚期热量限制的方法建立IUGR大鼠模型。造模组孕鼠自妊娠11d起给予对照组总热量50％饲料,新生鼠出生体重低于对照组新生鼠平均体重2个标准差者人选为IUGR组;对照组新生鼠即为正常组,对照组孕鼠自由进食。两组每窝各保留8只新生鼠继续饲养,仔鼠21d断奶后以标准饲料喂养至36周。选取第36周（中老年阶段）雄鼠为研究对象,实施腹腔葡萄糖耐量及胰岛素释放试验,运用逆转录聚合酶链反应（RT-PCR）方法检测胰腺组织中胰岛素合成相关基因[胰岛素基因1（Insulinl）、胰岛素基因2（Insulin2）以及胰-十二指肠同源盒基因-1（PDX-I）]的表达情况。两组间比较采用t检验分析。结果第36周,IUGR组大鼠胰重及胰重／体重比值明显低于正常组[分别为（4971±525）比（5844±398）mg和（0．58±0．05）％比（0．69±0．04）％,t=-2．65、-3．39,均P〈0．05]。糖负荷后各时点（30、60、120、180min）血糖值IUGR组均明显高于正常组[分别为30min：（17．9±1．5）比（16．1±1．1）mmol／L,60min：（13．4±1．1）比（11．7±1．4）mmol／L,120min：（10．1±0．8）比（8．6±1．0）mmol／L,180min：（8．9±1．0）比（7．6±0．9）mmol／L,t=2．31、2．37、2．77、2．34,均P〈0．05];糖负荷后各时点胰岛素分泌水平两组大鼠差异无统计学意义（t=1．66、-0．10、-0．65、-0．83、-0．58,均P〉0．05）。IUGR组大鼠胰腺组织中Insulinl基因表达较正常组明显减少（0．79±0．17比1．25±0．28,t=-2．78,P〈0．05）,而Insulin2、PDX-1基因表达差异均无统计学意义（t=-1．65、-1．46,均P〉0．05）。结论IUGR大鼠第36周糖耐量减退,胰腺组织中Insulinl基因表达下调。     

生长激素治疗宫内发育迟缓大鼠的骨组织形态计量学变化

目的　了解宫内发育迟缓 (IUGR)大鼠对促生长素 (生长激素 ,GH )治疗的生长反应。方法用限食法制作IUGR大鼠模型后 ,在各组仔鼠达到 3周龄时 ,随机分成 3组 (每组 10只 ) :对照组、GH +IUGR组、IUGR组。给GH +IUGR组大鼠注射GH 2周后 ,各组大鼠均被处死 ,用骨组织计量学方法检测GH治疗对IUGR大鼠骨骼的作用。结果　 5周龄时GH +IUGR组的血清GH水平、骨钙含量、碱性磷酸酶含量明显高于对照组和IUGR组 (均P <0 .0 1)。GH +IUGR组大鼠体重 ,干骺端骨小梁密度 ,骨干皮质骨厚度、皮质骨体积百分比、皮骨质内表面类骨质宽度、骨小梁表面平均类骨质宽度、骨小梁类骨质表面百分比、骨骺骨矿化沉积率、初级骨小梁骨宽度与IUGR组相比均明显增大 (均P <0 .0 1) ,但 10 0 μm磨片可见GH +IUGR组骨皮质中类骨质增多 ,孔状结构增加。结论　GH可以增加IUGR大鼠骨转换 ,增加松质骨骨量 ,但皮质骨密度有减低的趋势。     

Cerebral amino acid changes in an animal model of intrauterine growth retardation

As part of a series of experiments to ascertain the effects of prenatal malnutrition on brain development, we measured brain amino acids in an animal model of intrauterine growth retardation (IUGR) obtained by restriction of blood supply to the fetusin utero during the last 5 days of gestation. In the present study, amino acids were measured during development by HPLC as their O-phthaldialdehyde derivatives in cerebral cortex, cerebellum and hippocampus. In rats with IUGR, significant increase of alanine (by 20% to 50%) and taurine (by 20% to 80%) were observed prior to weaning in the cerebellum and the cerebral cortex respectively. Alanine levels were also increased in hippocampus. In control animals, at birth, activities of the GABA nerve terminal marker enzyme glutamic acid decarboxylase (GAD) were found to be 32%, 17%, and 11% of adult values in cerebellum, hippocampus and cerebral cortex respectively. Two-day-old rats with IUGR had significantly lower GAD activities in all brain regions. Thus, impairment of nutrient supply to fetal brain results in selective regional abnormalities of amino acids particularly in the cerebral cortex.     

Effects of intrauterine growth retardation and prematurity on spirometric flow values and lung volumes at school age in twin pairs

Lung volumes and pulmonary expiratory flow values were investigated in 67 children from multiple pregnancies (30 twins, one set of triplets, one set of quadruplets) at the age of 7–15 years. At birth, 30 of 67 children (44%) had intrauterine growth retardation (IUGR, birth weight <−2 SD or birth weight difference between twin-pairs >1.3 SD). The median gestational age was 35 weeks (range, 28–38 weeks), and the median birth weight was 2,050 g (800–3,150 g). Lung functions were measured with a heated pneumotachograph. Data were standardized using height-based reference equations. No differences were found in lung volumes between children with IUGR and those children who had normal birth weight. Gestational age did not correlate with either airway flow rates or lung volumes. Maximum mid-expiratory flow (FEF₅₀) did not correlate with standardized birth weight or with gestational age. In discordant twin pairs, the IUGR twins had significantly lower FEF₅₀ than their normal birth weight counterparts (p = 0.03, Z = −2.13). In the whole study group (67 children), children with IUGR had significantly lower FEF₅₀ than children with normal birth weight (p = 0.04; CI, 0.3–19.9). We propose that IUGR has the most pronounced effect on the growth of airways, and no detectable influence on lung volumes. This study confirms the crucial effect of appropriate intrauterine growth on subsequent growth on pulmonary airways. Pediatr Pulmonol. 1998; 25:367–370. © 1998 Wiley-Liss, Inc.     

Final height and intrauterine growth retardation

Approximately 10% of small for gestational age (SGA) children maintain a small body size throughout childhood and often into adult life with a decreased pubertal spurt. Growth hormone (GH) therapy increases short-term growth in a dose–dependent manner and adult height had now been well documented. Shorter children might benefit from a higher dose at start (50 μg/kg/day). The response to GH treatment was similar for both preterm and term short SGA groups and the effect of GH treatment on adult height showed a wide variation in growth response. As a whole, mean adult height is higher than −2 SDS in 60% of patients and 70% reached an adult height in their target height with better results with higher doses and combined GnRH analog therapy in those who were short at onset of puberty.     

宫内发育迟缓幼鼠胰岛素受体底物表达与胰岛素抵抗

采用RT-PCR和免疫组化研究胰岛素受体底物（IRS）1和IRS-2在宫内发育迟缓（IUGR）幼鼠组织中的表达与胰岛素抵抗的关系。采用母孕期饥饿法建立IUGR新生大鼠模型。IUGR组出生至3周龄肝组织IRS-2表达水平和骨骼肌组织IRS-1表达水平皆显著低于对照组，并诱导胰岛素抵抗，可能是IUGR易患代谢综合征的分子机制之一。     

Screening tests for intrauterine growth retardation: a comparison of umbilical artery Doppler to real-time ultrasound

In a study designed to compare Doppler umbilical artery velocimetry to ultrasound morphometric measurements in the prediction of intrauterine growth retardation, 636 paired ultrasound and Doppler umbilical artery examinations were performed between 24 and 40 weeks gestational age. Intrauterine growth retardation was defined as birth weight less than the tenth percentile per gestational age and 25 (9.2%) of the infants born in our study met this criteria. In general, when the gestational age was limited to less than 30 weeks, none of the tests were highly predictive of intrauterine growth retardation. Doppler umbilical artery systolic-to-diastolic ratios of greater than 3 had the highest sensitivity. However, due to inclusion of a large number of false-positives, it was considered a poor test. After 30 weeks, fetal abdominal circumference less than the tenth percentile had a greater sensitivity (45%) and positive predictive value (28%) than Doppler systolic-to-diastolic ratios greater than 3 (36% and 18%, respectively). Doppler ultrasound umbilical artery systolic-to-diastolic ratios are not more predictive of intrauterine growth retardation than ultrasound morphometric measurements.     

Effect of Kaiyu Qingwei Jianji on the morphometry and residual strain distribution of small intestine in experimental diabetic rats

INTRODUCTION Dysfunction of upper gastrointestinal tract (GI) is common among diabetic patients[1]. As many as 75% of patients visiting diabetes clinics report significant GI Symptoms[2,3]. Common complaints include dysphagia, early satiety, reflux, abdominal pain, nausea, vomiting, and diarrhea[2,3]. As with other complications of diabetes, the duration of the disorder and poor glycemic control seem to be associated with more severe GI problems[2,3]. Histologically, many experiments h…     

早期肠内营养对老年慢性心力衰竭患者血清炎症介质及瘦素的影响

目的 探讨早期肠内营养对老年慢性心力衰竭(CHF)患者心功能及血清炎症介质和瘦素等的影响. 方法 选取2017年6月至2019年1月在浙江医院住院的老年CHF患者80例,随机分为对照组38例和治疗组42例,两组患者在常规抗心力衰竭治疗下,对照组予自由饮食,治疗组予日常膳食联合肠内营养制剂治疗2～4 w,检测治疗前后两组...     

高脂大鼠抵抗素基因的上调表达及与胰岛素、瘦素的相关性

目的 观察SD大鼠高脂饮食状态下脂肪组织中抵抗素的表达及其与胰岛素抵抗以及糖尿病、瘦素等的关系。方法 采用RT—PCR、割胶纯化、基因构建测序的方法，证实为目的片段后，对高脂饮食SD大鼠的脂肪组织进行mRNA抽提，再以此为模板进行半定量RT—PCR扩增及Northern印迹分析。同时检测血清中胰岛素、瘦素水平，并行糖耐量试验、胰岛素释放试验等。结果 (1)成功构建了抵抗素的基因，并经测序证实。(2)与对照组相比，高脂饮食组大鼠脂肪组织中抵抗素表达明显升高，血糖水平、胰岛素水平以及瘦素水平升高。(3)高脂饮食组大鼠在4个月时下丘脑中瘦素受体表达较对照组明显降低。结论 抵抗素表达量的变化与饮食有关，抵抗素可能是胰岛素抵抗、糖尿病发病的一个前期信号，其作用可能与瘦素、瘦素受体有一定关系。     

Leptin mRNA表达的组织分布及在大鼠急性肠道损伤中的变化

目的:探讨leptin在急性炎症反应中的作用.方法:采集正常大鼠下丘脑、肺、肝、脾、胃、十二指肠、肾、附睾脂肪垫、睾丸等重要脏器标本,以RT-PCR法检测leptinmRNA表达的组织分布;并建立大鼠盲肠结扎穿孔模型,设立假手术组(A)和脂肪乳组(B)、单纯损伤组(C)、雌二醇组(D)、胰岛素组(E)等实验组,采用RT-PCR检测脂肪、肝及肺内leptinmRNA表达的变化.结果:正常大鼠的上述9种重要脏器内均有leptinmRNA表达,肾脏内含量最高而睾丸内含量最低.大鼠盲肠结扎穿孔12h后,与A组leptinmRNA表达水平相比,其在B组脂肪内表达显著增高而在肝、肺内表达显著降低,在C组肝内表达无显著差异而在脂肪、肺内表达显著降低,在D组肺内表达显著增高而在脂肪、肝内表达显著降低,在E组肺内表达无显著差异而在脂肪、肝内表达显著降低.脂肪乳对leptinmRNA表达的影响具有中枢分泌组织(脂肪)内诱导而外周脏器内抑制的双向模式.结论:LeptinmRNA表达水平在干预急性肠道损伤后能量代谢和神经-内分泌功能时发生敏感变化,提示leptin可能作为一种核心保护因子促进内环境的稳定.     

瘦素在儿童和青少年青春期发育中的作用

女性血清瘦素水平伴随青春期发育而升高 ;男性血清瘦素水平在G2 期 (Tanner分期 )达峰值后逐步下降 ,G5期再次升高。瘦素可能有启动和促进女性青春期发育的作用。对于男性可能有促进作用 ,但启动青春期的作用不显著。     

Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birthweight

Aims/hypothesis Low birthweight (LBW) and rapid postnatal weight gain, or catch-up growth, are independent risk factors for the development of obesity and diabetes during adult life. Individuals who are both small at birth and have postnatal catch-up growth are at the highest risk. We hypothesised that dietary interventions designed to attenuate catch-up growth in LBW subjects may have long-term beneficial consequences.Materials and methods We used our previously described mouse model of LBW-associated diabetes, created by restricting maternal food intake to 50% during the last week of gestation. Control (C) dams and dams that had been subjected to undernutrition (U) were then provided either chow ad libitum after delivery or 50% food restriction on a per-day basis from delivery until weaning. We designated the resulting four groups control-control (CC), undernutrition-control (UC), control-undernutriton (CU) and undernutrition-undernutrition (UU), indicating the prenatal and postnatal experimental conditions, respectively. Carbohydrate metabolism and adiposity were assessed prospectively in offspring until age 6 months.Results Males that were small at birth and exhibited early postnatal catch-up growth developed glucose intolerance and obesity by age 6 months. In contrast, LBW mice without catch-up growth (UU) remained smaller than controls (CC), and glucose intolerance and obesity was prevented. Similarly, mice with normal birthweight that had blunted catch-up growth (CU) were leaner and had better tolerance test than CC mice. Catch-up growth during the first week of life correlated better than birthweight with glucose, fat mass and glucose tolerance up to 6 months of age.Conclusions/interpretation Prevention of early catch-up growth reversed the development of glucose intolerance and obesity in our mouse model of LBW-associated diabetes.     

瘦素对人脐静脉内皮细胞血管内皮生长因子表达的影响

目的:探讨瘦素对人脐静脉内皮细胞(HUVECs)血管内皮生长因子(VEGF)表达的影响。方法:用不同浓度的瘦素刺激原代培养的HUVECs,检测HUVECs表达VEGF的情况。结果:在相同作用时间下,随着瘦素浓度的升高,VEGF蛋白及VEGF mRNA的表达也随之升高,经统计学检验有相关性;在相同瘦素浓度下, 随着作用时间的延长,VEGF蛋白及VEGFmRNA的表达也随之升高,且有相关性。结论:瘦素可以刺激HU- VECs表达VEGF而且呈时间和剂量相关性。     

Factors associated with growth patterns from birth to 18 months in a Beninese cohort of children

The aim of this study was to analyze factors influencing the growth pattern of children from birth to 18 months. A longitudinal prospective study was conducted in three maternity wards in Southern Benin. Inclusion took place between June 2007 and July 2008; children were followed-up until 18 months of age. Height-for-age and weight-for-height Z-scores were computed using the newborn's anthropometric measurements taken at delivery, every month up to 6 months and then quarterly. Infant and young child feeding (IYCF) practices and malarial morbidity were recorded. Gestational age was estimated using the Ballard method; William's sex-specific reference curve of birth weight-for-gestational-age was used to determine intrauterine growth retardation (IUGR). Analyses were performed on 520 children using a linear mixed model. Low birth weight (coef = −0.43; p = 0.002), IUGR (coef = −0.49; p < 0.001), maternal short stature (coef = −0.25; p = 0.001) and maternal low weight status (coef = −0.19; p = 0.006) were significantly associated with growth impairment. Only LBW (coef = −0.28; p = 0.05) and maternal low weight status (coef = −0.23; p = 0.004) were associated with wasting. A good IYCF score was positively associated with weight gain (coef = 0.14; p < 0.001) whereas we found a paradoxical association with length (coef = −0.18; p < 0.001). Malaria morbidity was not associated with growth. LBW, IUGR and maternal low weight status and height were important determinants of children's growth. These results reinforce and justify continuing public health initiatives to fight IUGR and LBW and break the intergenerational cycle of malnutrition.