Ghrelin mRNA和蛋白在小于胎龄仔鼠胃底组织中表达的变化

目的了解胃底组织Ghrelin mRNA和蛋白表达与小于胎龄(SGA)仔鼠追赶生长的关系。方法采用妊娠中后期食物摄入限制法获得SGA和适于胎龄(AGA)仔鼠,并设对照组。孕鼠分娩后收获仔鼠,分别于0、20、40日龄3个时间点每组随机抽取仔鼠10只,取其胃底组织。采用实时荧光定量PCR法测定其Ghrelin mRNA,免疫组织化学法测定Ghrelin蛋白在各组仔鼠胃底组织中的表达。结果0日龄限食组SGA仔鼠胃底组织Gherlin mRNA表达高于限食组AGA仔鼠和对照组AGA仔鼠(Pa<0.05);20日龄和40日龄的SGA未追赶生长仔鼠、SGA追赶生长仔鼠和对照组AGA仔鼠胃底组织Gherlin mRNA表达均无统计学差异(Pa>0.05)。0日龄限食组SGA仔鼠胃底组织Ghrelin免疫阳性细胞的积分光密度(A)值高于限食组AGA和对照组AGA仔鼠(Pa<0.05);20日龄SGA追赶生长仔鼠胃底组织中Ghrelin免疫阳性细胞的A值高于SGA未追赶生长仔鼠和对照组AGA仔鼠(Pa<0.05);40日龄时3者间无统计学差异(P>0.05)。结论0日龄SGA仔鼠Ghrelin mRNA在胃底组织中表达增加,提示Ghrelin可能在宫内就开始参与宫内发育迟缓胎鼠的生理调节或病理过程,或是宫内的营养状况和环境变化对胎鼠胃底细胞的生理功能产生了影响,使Ghrelin mRNA表达上调;20日龄追赶生长SGA仔鼠胃底Ghrelin表达的变化进一步提示,Ghrelin可能参与了SGA早期的追赶生长调控。     

Ghrelin及受体GHSR表达变化与宫内发育受限仔鼠追赶生长的关系

目的：了解Ghrelin及生长激素释放促分泌素受体（GHSR）表达变化与宫内发育受限（IUGR）仔鼠追赶生长的关系。方法：采用妊娠期食物限制法建立IUGR大鼠模型,孕鼠分娩后,获得限食小于胎龄（SGA）仔鼠和限食适于胎龄（AGA）仔鼠为实验组,不限食适于胎龄（AGA）仔鼠为对照组。于0、20、40日龄取胃底和下丘脑组织,实时荧光定量PCR法（real-time FQ-PCR）分别测定Ghrelin mRNA和GHSR mRNA;免疫组织化学法测定Ghrelin蛋白和GHSR蛋白。结果：0日龄限食SGA组仔鼠胃底组织中Gherlin mRNA和蛋白表达均高于限食AGA组和对照组,下丘脑GHSR mRNA的表达低于限食AGA组和对照组;20日龄SGA组追赶生长仔鼠胃底Ghrelin蛋白、下丘脑GHSR mRNA和蛋白的表达高于SGA未追赶生长和对照组仔鼠;40日龄时3组间则差异无统计学意义（P>0.05）。结论：Ghrelin-GHSR可能参与了宫内IUGR胎鼠的生理调节或病理过程,且可能在出生后参与了SGA个体早期追赶生长的调控。     

小于胎龄儿相关因素的研究

为了解不同类型胎儿体格发育(出生体重、身长、头围)情况及小于胎龄儿相关因素,自1999年5月～2000年12月,对在我院分娩的单胎活产新生儿及其母亲424对,进行前瞻性调查.结果显示小于胎龄儿(SGA)36例,发生率为8.5%,适于胎龄儿(AGA)294例,大于胎龄儿(LGA)94例,SGA组除出生体重外,身长、头围三项指标均低,与AGA组有非常显著意义(P值均＜0.001).影响SGA体格发育Logis-tic回归分析最主要危险因素为母孕早期剧吐、被动吸烟、贫血、羊水量过少和母患妊高征.母亲身高、文化程度、胎盘重量与胎儿体格发育呈正相关.SGA组新生儿生后五天内发病率最高为33.3%,与AGA组的2.7%比较有非常显著意义(P＜0.01).因此,防治常见妊娠合并症,加强孕期营养,提高自我保护意识,将有助于降低SGA发生.     

小于胎龄儿相关因素的研究

为了解不同类型胎儿体格发育（出生体重，身长，头围）情况及小于胎龄儿相关因素，自1999年5月－2000年12月，对在我院分娩的单胎活产新生儿及其母亲424对，进行前瞻性调查。结果显示：小于胎龄儿（SGA）36例，发生率为8．5％，适于胎龄儿（AGA）294例，大于胎龄儿（LGA）94例，SGA组除出生体重外，身长，头围三项指标均低，与AGA组有非常显著意义（P值均＜0．001），影响SGA体格发育Logistic回归分析：最主要危险因素为母孕早期剧吐，被动吸烟，贫血，羊水量过少和母患妊高征，母亲身高，文化程度，胎盘重量与胎儿体格发育呈正相关，SGA组新生儿生后五天内发病率最高为33．3％，与AGA组的2．7％比较有非常显著意义（P＜0．01），因此，防治常见妊娠合并症，加强孕期营养，提高自我保护意识，将有助于降低SGA发生。     

小于胎龄鼠肝脏肥胖基因Lipin2的表达及其意义

目的 探讨小于胎龄(SGA)鼠肝脏中肥胖基因lipin2表达的动态变化及其意义.方法 选取健康成年SD大鼠,建立孕期全程低蛋白SGA鼠模型,随机分为适于胎龄(AGA)组和SGA组,每组24只仔鼠.选择1d、7d、21 d和56 d作为观察点,测定其体质量及头臀长,留取肝脏组织,采用反转录(RT) -PCR和蛋白质免疫印迹技术(Western blot)检测其肝组织中lipin2 mRNA和蛋白的动态表达.结果 1.体质量指数(BMI):1 dSGA鼠BMI较AGA组降低(P ＜0.05)；56 d SGA鼠的BMI较AGA组升高(P＜0.01).2.lipir2 mRNA和蛋白的表达:1 d SGA组低于AGA组(Pa＜0.05),7d和56 d SGA组均高于AGA组(Pa＜0.05).3.BMI与56 d大鼠lipin2蛋白表达量呈高度正相关(r=0.713,P=0.009).结论 SGA鼠出生时体态瘦小,后出现追赶生长,青春期末期成年大鼠表现出肥胖倾向.lipin能敏感地反映不同阶段宫内发育迟缓仔鼠肝脏物质代谢情况,提示其参与了SGA鼠的糖脂代谢紊乱过程,lipin基因表达的改变可能为SGA鼠引起成年期代谢综合征发病机制之一. .     

新生大鼠重度缺氧缺血性脑损伤模型的建立

目的 对经典Rice法进行改良,制作新生大鼠重度缺氧缺血性脑损伤(HIBD)模型,应用多种方法鉴定建模是否成功,为进一步研究重度HIBD的治疗提供信息.方法 7日龄新生大鼠左侧颈总动脉结扎并剪断后,置于密闭缺氧箱中,通入8%O2+92%N2混合气体2 h,密闭缺氧箱部分置于39℃水浴箱中保持环境温度恒定.不同时间点进行行为学检测、大脑解剖观察及大脑重量测定,取标本进行病理检测.结果 用该法建模后,模型鼠的运动行为落后,大体解剖、大脑重量、HE染色及Nissl染色均有明显改变.结论 经改良的建模方法成功可行,为进一步对重度HIBD的治疗提供了可靠的模型.     

小于胎龄儿大脑的发育及与适于胎龄儿的比较

人脑生长的关键期在妊娠中期至生后二年,小于胎龄儿(SGA)的畸形发生率与死亡率都比适于胎龄儿(AGA)高,出生后体格及智能发育亦常受到影响,一些SGA出生后智能发育落后,是否与其在宫内脑发育受到影响有关?为了了解SGA大脑的发育情况,我们应用颅脑超声对SGA大脑发育情况进行了观察,并与AGA婴儿进行比较,现报告如下。对象和方法一、对象1996年11月～1997年11月在我院的SGA共48例,男21例,女27例,其中足月SGA36例,胎龄为39.7±1.4周,出生体重为2453.3±310.7g;早产SGA12例,胎龄为35.1±1.6周,出生体重为1757±298.7g。AGA共151例,男91…     

不同程度小于胎龄儿发生的影响因素分析

目的 探讨不同程度小于胎龄儿（small for gestational age, SGA）发生的影响因素,为早期识别重度SGA的发生提供依据。方法 回顾性收集2018年1月—2022年12月北京大学人民医院产科出生的新生儿及其母亲围产期资料。新生儿分为重度SGA组（出生体重低于同胎龄同性别婴儿的第3百分位数）、轻度SGA组（出生体重≥第3百分位数且<第10百分位数）和非SGA组（出生体重≥第10百分位数）。采用有序多分类logistic回归模型分析不同程度SGA发生的影响因素。结果 共纳入14 821例新生儿,其中重度SGA组258例（1.74%）,轻度SGA组902例（6.09%）,非SGA组13 661例（92.17%）。早产儿比例和死产比例均为重度SGA组>轻度SGA组>非SGA组（P<0.0125）;重度SGA组与轻度SGA组新生儿窒息比例均大于非SGA组（P<0.0125）。有序多分类logistic回归分析显示：母孕前消瘦（OR=1.838）、母孕前肥胖（OR=3.024）、体外受精-胚胎移植（OR=2.649）、妊娠合并子痫前期（OR=1....     

13C-尿素呼气试验与儿童幽门螺杆菌感染及胃黏膜炎症组织学改变的相关性研究

目的 探讨13C-尿素呼气试验(13C-UBT)定量检测结果与幽门螺杆菌定植数量及胃黏膜炎症程度的关系.方法 选择具有上消化道症状的患儿进行13C-UBT检测,将检测结果阳性(DOB值8‰≥4.0)的95例患儿作为研究对象,对其进行胃镜检查,同时取胃黏膜做组织病理学检查,对13 C-UBT定量结果与胃内幽门螺杆菌感染的严重程度及胃黏膜炎症之间的差异进行相关性分析.结果 胃黏膜幽门螺杆菌重度感染组与轻、中度感染组之间,DOB值差异具有统计学意义(P＜0.05).胃黏膜炎症重度与轻、中度之间的DOB值差异具有统计学意义(P＜0.05).DOB值与胃黏膜幽门螺杆菌的定植量及胃黏膜炎症程度之间有一定的相关性.结论 13 C-UBT定量检测结果能提示胃内幽门螺杆菌定植数量,但两者之间缺乏精确的定量关系.DOB值与胃黏膜炎症程度之间呈正相关.     

邻苯二甲酸二丁酯对雄性大鼠生殖器官的影响

目的 探讨邻苯二甲酸二丁酯对雄性仔鼠生殖器官的毒性作用及机制.方法 取8周龄SD大鼠,雌性32只,雄性16只,随机分为对照组和染毒组（邻苯二甲酸二丁酯组,即DBP组）.于怀孕第13～21天,对照组按1 mL/只灌服花生油,DBP组按500mg/kg灌服邻苯二甲酸二丁酯.分娩后即对新生鼠点数,观察新生鼠外生殖器,称重和测量肛生殖距离,判断有无尿道下裂畸形.仔鼠出生后第4、15、25及90天,抽取外周静脉血,检测睾酮水平;解剖、记录性腺位置及发育情况,取出性腺,称重,常规病理学检查.结果 新生雄性仔鼠出生后DBP组平均体重明显低于对照组,P＜0.05;DBP组16只孕鼠共产雄性仔鼠91只,隐睾17只,尿道下裂7只,对照组未发现隐睾及尿道下裂雄性仔鼠;出生后第90天,对照组体重、睾丸、附睾及前列腺精囊重量重于DBP组;出生后第15、25、90天血睾酮水平,对照组高于DBP组,P＜0.05.结论 邻苯二甲酸二丁酯对雄性大鼠生殖器官的发育有明显毒性作用,可能是通过影响睾酮的合成、分泌等发挥作用.     

Effects of oxytocin treatment early in pregnancy on fetal growth in ad libitum-fed and food-restricted rats.

The effects of oxytocin on fetal and placental growth and on maternal weight gain and accumulation of body fat were studied in ad libitum-fed and food-restricted (receiving 70% of the food intake of the ad libitum-fed group) pregnant rats. Further, a possible role of the IGF axis in mediating oxytocin-induced changes was assessed. Pregnant rats were injected subcutaneously once a day during gestational d 1-5 with saline or oxytocin (1 mg/kg). Ad libitum-fed oxytocin-treated pregnant rats had higher circulating levels of IGF-I, larger placentas, fetuses, and newborn pups and contained less body fat at the end of pregnancy. In food-restricted dams, oxytocin-treatment had no effect on fetal and placental growth. Additionally, food restriction attenuated the normal increase in IGF binding protein-3 protease proteolysis during pregnancy. The results show that oxytocin may affect maternal adaptations to pregnancy and stimulate fetal growth. We suggest that this effect may be mediated by increased IGF-I in ad libitum-fed animals, whereas food restriction may block this effect by resulting in low levels of circulating IGF-I and by attenuating the pregnancy-associated increase in IGF binding protein-3 protease activity and, thereby, further compromise IGF bioavailability.     

Effects of maternal caffeine ingestion on the perinatal cerebrum

The cerebra of fetal rats from dams given 0.04 or 0.02% caffeine in drinking water ad libitum before and/or during pregnancy were examined on gestational day 21. A low placental weight was induced by caffeine ingestion for a long time throughout premating and pregnancy. A greater reduction in the fetal weight of the cerebrum than that of the body was observed with caffeine ingestion during pregnancy of levels of 1.5-3.0 micrograms caffeine/ml or g wet weight in dams and fetuses. In the cerebra of offspring, the levels of caffeine and theophylline did not change for 4 h after birth, and theophylline was not detected at all after intraperitoneal injection of caffeine. Thus, maternal caffeine should be warned against the fetal cerebral function.     

Sex-specific differences in birth weight due to maternal smoking during pregnancy

Introduction We investigated the sex-specific risk of maternal smoking during pregnancy on the birth weight and the proportion of small-for-gestational-age (SGA) newborns in 888,632 (49.9%) of 1,815,318 singleton births (ca. 80% of all singleton births in Germany from 1995 to 1997) in whom data on maternal cigarette consumption were available.Results and discussion Newborns below the 10th percentile for weight and duration of pregnancy were classified SGA. Maternal smoking during pregnancy lowers the mean birth weight and increases the risk of SGA newborns. The negative effect depends on the daily number of cigarettes consumed, and is greater in girls than in boys. In non-smokers, 9.8% of the newborns were SGA, with a sex-ratio of females:males=1, but this percentage increased with increasing number of cigarettes consumed (p<0.001), as did the sex-ratio, i.e. the negative effect of smoking on growth was greater in girls than in boys. In mild smokers (1–5 cigarettes/day), the risk of giving birth to an SGA girl was 1.7275-fold (95% CI: 1.7266–1.7284) above normal, but was 1.7143-fold (95% CI: 1.7137–1.7150) in boys. More than 21 cigarettes/day increased the risk of SGA 3.15-fold for a boy, but 3.51-fold for a girl (p<0.001).Conclusion In conclusion, particularly in heavy smokers, the negative effect of maternal smoking during pregnancy on the mean birth weight and risk of SGA is significantly greater in newborn girls than in newborn boys.     

Definition of fetal growth restriction according to constitutional growth potential

Identification of newborn babies with fetal growth restriction remains a problem both from the multi-factorial aspect of fetal growth and from statistical definition. Besides the usual terms: "Small for gestational age" (SGA) and intrauterine growth retardation (IUGR), often used synonymously, the term "fetal growth retardation" was recently introduced in reference to the genetic growth potential of infants. From a sample of 72,000 births, we have designed a statistical model in order to estimate the expected birth weight taking into account gestational age, sex, birth rank, maternal age, height and pregravid weight, we then calculated an individual limit of birth weight under that a newborn must be considered as having a "fetal growth restriction" quoted FwGR. This new approach allowed us to identify 2 groups of newborns with FGR, one classically identified as SGA (noted FwGR(I)) (3.9%), and the other newly identified as FGR (noted FwGR(II)) (1.4%). In contrast, this approach allowed us to identify a group of "constitutionally small" infants according to their constitutional growth potential (1.1%). In other words, among infants usually defined as SGA (5%), 22% appeared in fact to be "constitutionally small" and therefore misclassified. As an initial validation, we observed that the proportion of maternal hypertension during pregnancy was low in the "constitutionally small" infants (close to that of the normal group), and three times higher in the newly identified group FwGR(II) than in the normal group. Following these results, it seems to be meaningful to follow-up this new group of FwGR(II) infants, in terms of catch-up growth and neurodevelopmental outcome.     

左旋精氨酸对低出生体重仔鼠PI3K和PKB的影响

目的：生命早期应用左旋精氨酸（L-Arg）干预低出生体重仔鼠,检测其肝脏磷脂酰肌醇-3-激酶（PI3K）和蛋白激酶B(PKB)的表达,探讨L-Arg对改善胰岛素抵抗的影响。方法：以孕期低蛋白饮食法建立低出生体重仔鼠模型,18只孕鼠随机分为对照组、模型组和干预组,每组6只。对照组孕期给予21%正常蛋白饲料建立正常出生体重仔鼠模型,模型组及干预组孕期给予10%低蛋白饲料建立低出生体重仔鼠模型,3组孕鼠所生仔鼠分别纳入仔鼠对照组、模型组、干预组。生后21 d 仔鼠的哺乳期内,3组孕鼠均给予21%正常蛋白饲料喂养,对照组及模型组给予正常饮用水喂养,干预组给予富含L-Arg（200 mg/kg.d）的饮用水喂养。断乳后,3组仔鼠均给予21%正常蛋白饲料及正常饮用水喂养。于仔鼠生后1 周、3 周、8 周时,分别留取3组仔鼠的肝脏标本,用Western blot法检测肝脏PI3K和PKB的蛋白表达。结果：1 周时干预组仔鼠肝脏PI3K的蛋白表达高于模型组（P=0.045）,且与正常组相比差异无统计学意义（P=0.503）。8 周时干预组仔鼠肝脏PKB蛋白表达明显高于模型组（P=0.039）,且与正常组比较差异无统计学意义（P>0.05）。结论：生命早期补充L-Arg可促进蛋白质的合成,增加肝脏PI3K及PKB的蛋白表达,促进胰岛素信号传导,改善胰岛素抵抗。     

表没食子儿茶素-3-没食子酸酯对宫内生长受限大鼠肝脏脂代谢的影响和机制

目的 探讨表没食子儿茶素-3-没食子酸酯（EGCG）对宫内生长受限（IUGR）大鼠肝脏脂代谢的影响和机制。方法 采用母鼠孕期全程限食法建立IUGR大鼠模型,随机分为IUGR组和EGCG组,EGCG组大鼠在离乳后用含EGCG的饮用水喂养至10周,同时设立正常对照组,每组8只。13周龄时,测量各组大鼠体重后,采集大鼠血液及肝脏组织标本,检测各组大鼠血清空腹总胆固醇（TC）、甘油三酯（TG）、游离脂肪酸（FFA）、血糖（FPG）、胰岛素（FINS）和肝脏脂质水平,计算稳态模型评估胰岛素抵抗（HOMA-IR）和脂肪组织胰岛素抵抗（adipo-IR）,观察肝脏组织病理切片,并采用实时荧光定量PCR法检测肝脏相关基因的相对表达水平。结果 13周龄时,各组大鼠体重比较差异无统计学意义（P=0.067）。各组间的FPG、FFA、FINS、HOMA-IR和adipo-IR水平比较差异均有统计学意义（P < 0.05）。各组间的血清TC和TG水平比较差异无统计学意义（P > 0.05）,但在肝脏中IUGR组TC和TG水平均明显高于EGCG组（P < 0.05）。油红染色结果提示,IUGR大鼠的肝脏脂肪储积明显增加,而EGCG能够改善该现象。PCR结果显示,与对照组相比,IUGR组的Ampk mRNA及Adipor1 mRNA表达水平降低,Srebf1 mRNA表达水平增加（P < 0.05）,EGCG能逆转IUGR大鼠Ampk mRNA及Srebf1 mRNA的表达水平,且与对照组比较差异无统计学意义（P > 0.05）。结论 早期EGCG干预可能通过Ampk/Srebf1通路下调脂肪酸的从头合成,并通过改善肝细胞的胰岛素抵抗,从而降低IUGR大鼠的肝脏脂肪积累。     

Treadmill training enhances glucose tolerance more in pregnant than in virgin rats

To determine whether aerobic training throughout gestation modifies glucose tolerance, female Wistar rats were mated or kept nonpregnant and run or not on a 10 degrees slope treadmill for 5 days/week at 20 m/min, starting with a 20-min run, and with a progressive daily increase of 5 min, reaching a 75-min run on the 20th day of protocol or gestation. The exercise protocol did not modify food intake, maternal and fetal weights, litter size or blood lactic acid levels. The rise in blood glucose after an oral glucose load (2 g/kg body weight) did not differ between trained and untrained nonpregnant rats but was lower in trained than in untrained pregnant rats. In the untrained rats the rise in plasma insulin levels after the glucose load was much greater in pregnant than in nonpregnant rats; in trained rats this difference between groups was attenuated by the greater effect of exercise decreasing the plasma insulin response to the glucose load in pregnant than in nonpregnant rats. Thus, an aerobic exercise protocol that does not modify the outcome of pregnancy does significantly reduce the altered oral glucose tolerance in pregnant rats and only has a minor effect in nonpregnant rats.