瘦素及瘦素受体与胎儿生长受限的关系

目的　探讨母血、脐血和胎盘瘦素及瘦素受体表达与胎儿生长发育的关系。　方法　采用ELISA法和逆转录定量聚合酶链反应检测 2 3例小于胎龄儿 (SGA)和 4 4例适于胎龄儿 (AGA)母血、脐血瘦素和可溶性瘦素受体 (sOB R)浓度 ,胎盘组织瘦素mRNA和瘦素受体 (OB R)mRNA表达水平。　结果　SGA组和AGA组母血瘦素浓度分别为 (33.80± 14 .0 5 ) μg/L和 (2 7.0 1± 14 .81)μg/L(P =0 .0 89) ;母血sOB R浓度分别为 (2 5 .5 6± 10 .78) μg/L和 (2 6 .6 1± 9.6 9) μg/L(P =0 .70 1) ;脐血瘦素浓度分别为 (6 .79± 4 .5 9) μg/L和 (16 .30± 11.6 1) μg/L(P =0 .0 0 0 ) ;脐血sOB R浓度分别为 (18.2 4± 6 .0 2 ) μg/L和 (13.80± 4 .39) μg/L(P =0 .0 0 2 ) ;胎盘组织瘦素mRNA表达分别为 0 .77±0 .13和 0 .99± 0 .2 9(P =0 .0 0 2 ) ;OB RmRNA表达分别为 0 .5 6± 0 .2 1和 1.0 7± 0 .2 7(P =0 .0 0 0 )。脐血瘦素、胎盘瘦素和OB RmRNA表达水平分别与新生儿体重、身高、体脂、头围呈正相关 ,脐血sOB R分别与上述新生儿指标呈负相关。　结论　脐血瘦素浓度降低和胎盘瘦素、OB R受体表达低下与胎儿生长受限密切相关 ,脐血瘦素可能通过与不同剪接体的受体结合实现对胎儿生长发育的调控作用。     

多囊卵巢综合征患者血清瘦素水平的测定及意义

目的　探讨多囊卵巢综合征 (PCOS)患者血清瘦素水平变化及其临床意义。方法　采用放射免疫法测定 5 3例PCOS患者血清瘦素、胰岛素水平并与 2 0例月经周期正常妇女作对照。结果　PCOS组空腹血清瘦素水平 (19 72± 18 11) μg/L ,对照组 (8 0 6± 3 2 8) μg/L ,两组比较差异有显著性 (t =4 498,P <0 0 5 ) ;PCOS组空腹胰岛素水平 (11 78± 8 0 3)mIU/L ,明显高于对照组 [(7 95± 2 2 4)mIU/L],差异有显著性 (t=3 16 3,P <0 0 5 ) ,PCOS组血清瘦素水平与胰岛素呈正相关。结论　瘦素和胰岛素可能共同参与PCOS的病理过程 ,检测血中瘦素水平 ,对于PCOS促排卵治疗的效果判断可能具有一定的意义     

妊娠期糖尿病母儿血清瘦素水平和胎盘瘦素表达及其与胰岛素的关系

目的 :探讨妊娠期糖尿病母儿瘦素水平变化和胎盘瘦素mRNA表达 ,以及与胰岛素的关系。方法 :1999年 10月至 2 0 0 2年 2月 ,采用放射免疫法检测 18例妊娠期糖尿病孕妇 (观察组 )、2 0例正常孕妇 (对照组 )母儿血胰岛素和瘦素水平。采用逆转录聚合酶链反应 (RT PCR)和荧光定量分析法检测胎盘瘦素mRNA表达水平。结果 :观察组母血胰岛素、母血瘦素、脐血胰岛素、脐血瘦素和胎盘组织mRNA表达水平高于对照组 (P <0 .0 5 ) ,观察组母血瘦素与母血胰岛素水平与新生儿体重正相关 (r =0 .5 0 ,0 .4 8;P <0 .0 5 ) ,脐血瘦素和胰岛素水平与胎盘瘦素mRNA表达水平正相关 (r =0 .5 1,0 .5 3;P <0 .0 5 )。结论 :妊娠期糖尿病母儿同时存在高瘦素血症和高胰岛素血症 ,高胰岛素血症上调胎盘组织瘦素mRNA的表达 ,与巨大儿发生有关。     

瘦素与妊娠期糖尿病胰岛素抵抗的关系

目的　探讨瘦素与妊娠期糖尿病 (GDM)胰岛素抵抗 (IR)关系及在GDM发病机制中的作用。方法　应用放射免疫法测量 32例GDM妇女、 30例正常糖耐量妊娠妇女 (NGT)的空腹瘦素、C肽水平及空腹胰岛素和 75g葡萄糖耐量试验 (OGTT)后 2h的胰岛素水平。应用稳态模型胰岛素抵抗指数 (HOMA -IR)及胰岛分泌功能指数 (HBCI) ,比较两组HOMA -IR及HBCI的差异 ,分析两组空腹瘦素与IR之间的关系。结果　①GDM组HOMA -IR (2 3± 0 3)高于NGT组 (1 4± 0 4 ) ,差异有显著性 (P <0 0 1) ;两组间HBCI比较差异无显著性 (P >0 0 5 )。②GDM组血清瘦素水平 (2 4 7± 2 2 )ng ml高于NGT组 (2 0 3± 1 5 )ng ml,两组之间比较差异有显著性 (P <0 0 5 )。相关分析表明 ,在GDM组瘦素与HOMA -IR呈正相关 (rLeptin =0 5 4 8,P <0 0 0 1) ,在NGT组二者之间无相关性 (rNGT =0 2 2 1P >0 0 5 )。结论　妊娠期IR程度增加 ,可能是GDM主要的发病机制之一。瘦素与GDM胰岛素抵抗有关 ,可能参与GDM的发病     

妊娠期糖代谢异常孕妇血清瘦素水平及其与胰岛素和血糖关系的研究

目的　探讨妊娠期糖代谢异常孕妇血清瘦素水平及其与胰岛素和血糖的关系。方法　采用放射免疫法 ,测定 36例妊娠期糖代谢异常孕妇 (糖代谢异常组 )和 2 4例正常孕妇 (正常妊娠组 )的空腹及口服 50g葡萄糖后 3h的血清瘦素水平 ;采用电化学发光法测定两组孕妇的空腹血清胰岛素水平 ;采用低压液相色谱分析法测定两组孕妇的糖化血红蛋白 ;采用葡萄糖氧化酶法测定两组孕妇的口服 50g葡萄糖后 1h的血糖水平。结果　 (1 )糖代谢异常组孕妇血清瘦素水平为 (1 4 9± 4 3) μg/L ,正常妊娠组为 (1 0 0± 1 8) μg/L ,两组比较 ,差异有极显著性 (P <0 0 1 ) ;(2 )糖代谢异常组孕妇空腹血清胰岛素、糖化血红蛋白、服糖后 1h血糖水平分别为 (1 2 9± 4 3)mU/L、 (6 1± 1 1 ) %、(1 1 0±1 4)mmol/L ;正常妊娠组孕妇分别为 (8 6± 3 2 )mU/L、(4 5± 1 0 ) %、(7 8± 1 2 )mmol/L。糖代谢异常组孕妇血清瘦素水平与空腹血清胰岛素、糖化血红蛋白、服糖后 1h的血糖水平呈明显的正相关关系 ,相关系数 (r)分别为 0 835、0 758、0 561。结论　妊娠期糖代谢异常孕妇空腹血清瘦素水平升高 ,其瘦素水平的高低与空腹血清胰岛素及血糖水平相关     

妊娠期糖尿病孕妇血清肿瘤坏死因子α水平变化与胰岛素抵抗关系的研究

目的　探讨妊娠期糖尿病孕妇血清肿瘤坏死因子α(TNF α)水平变化与胰岛素抵抗的关系。方法　采用酶联免疫吸附试验测定 4 2例妊娠期糖尿病孕妇 (GDM组 )、4 0例正常妊娠晚期孕妇 (正常妊娠组 )空腹血清TNF α水平 ;同时测定两组孕妇空腹血糖、C肽、胰岛素、糖化血红蛋白(HbA1c)水平。并且根据公式计算两组孕妇的胰岛素敏感指数 (ISI) ,以评价胰岛素抵抗程度。结果(1)GDM组孕妇空腹血清TNF α水平为 (5 2± 1 6 )ng/L ,正常妊娠组孕妇为 (4 5± 0 5 )ng/L ,两组比较 ,差异有极显著性 (P <0 0 1) ;GDM组孕妇ISI为 - 4 3± 0 4 ,正常妊娠组为 - 3 8± 0 3,两组比较 ,差异有极显著性 (P <0 0 1)。 (2 )GDM组孕妇空腹血糖、胰岛素、C肽水平分别为 (5 5± 0 7)mmol/L、(13 4± 3 8)mU/L、(1 6± 0 4 )nmol/L ,正常妊娠组孕妇空腹血糖、胰岛素、C肽水平分别为(4 9± 0 4 )mmol/L、(9 3± 2 5 )mU/L、(1 2± 0 3)nmol,两组比较 ,差异有极显著性 (P <0 0 1) ;GDM组孕妇HbA1c为 (5 6± 0 5 ) % ,正常妊娠组孕妇为 (5 3± 0 5 ) % ,两组比较 ,差异有显著性(P <0 0 5 )。 (3)GDM组孕妇空腹血清TNF α水平与ISI呈显著负相关 (r=- 0 70 3,P <0 0 1) ,分别与空腹血糖、C肽、HbA1c呈显著正相关 (r     

妊娠妇女及新生儿脐血瘦素水平与体重,胰岛素,C—肽,胰岛 …

目的　探讨妊娠晚期妇女及新生儿脐血瘦素水平与孕妇体重及新生儿体重的关系 ,以及新生儿脐血瘦素水平与C 肽、胰岛素、胰岛素样生长因子 Ⅱ (IGF Ⅱ )等的关系。方法　采用放射免疫法测定 5 0例孕 37～ 38周正常妊娠妇女 (研究组 )及其新生儿、2 9例健康未妊娠妇女 (对照组 )的血瘦素水平 ,并同时测定新生儿脐血C 肽、胰岛素、IGF Ⅱ的水平等。结果　 (1)妊娠晚期妇女血瘦素水平为 (13.6 2± 3.6 8) μg/L ,明显高于对照组妇女的 (6 .6 0± 3.0 4) μg/L及新生儿脐血瘦素的 (8.0 5± 4.6 1) μg/L。 (2 )妊娠晚期妇女血瘦素水平与本身体重及体重指数明显相关 (r分别为 0 .33、0 .35 ,P<0 .0 5 ) ;妊娠晚期妇女血瘦素水平与新生儿体重无明显相关 (r=0 .10 ,P >0 .0 5 )。 (3)新生儿脐血瘦素水平与其体重、体重指数明显相关 (r分别为 0 .5 4、0 .49,P <0 .0 0 1) ;而与妊娠晚期妇女血瘦素水平无明显相关 (r=0 .19,P >0 .0 5 )。 (4 )对照组妇女血瘦素水平与其体重、体重指数明显正相关 (r分别为 0 .72、0 .78,P <0 .0 0 1)。 (5 )新生儿脐血C 肽为 (0 .86± 0 .35 ) μg/L ,胰岛素为 (8.49± 4.76 )mU/L ,IGF Ⅱ为 (0 .2 18± 0 .0 76 ) μg/L ;新生儿脐血瘦素水平与C 肽明显相关 (r=0 .37,P <0 .0 5 )     

瘦素及胰岛素样生长因子-Ⅰ与胎儿生长受限的关系

目的　探讨瘦素及胰岛素样生长因子Ⅰ (IGF Ⅰ )与胎儿生长受限 (FGR)的关系。方法　采用放射免疫法和免疫放射法测定 30例FGR孕妇 (FGR组 )和 80例正常孕妇 (对照组 )的血清及脐血瘦素、IGF Ⅰ水平 ,并对其结果进行相关性分析。结果　FGR组血清瘦素水平与对照组比较 ,差异无显著性 (P >0 0 5 ) ;FGR组血清IGF Ⅰ水平明显低于对照组 (P <0 0 5 ) ,FGR组脐血瘦素、IGF Ⅰ水平均明显低于对照组 (P <0 0 5 ,P <0 0 1 ) ;两组孕妇血清瘦素、IGF Ⅰ水平与脐血瘦素、IGF Ⅰ水平无相关性 (r =0 1 85 ,r =0 2 6 2 ,P >0 0 5 ) ;脐血瘦素水平与新生儿出生体重呈正相关 (r =0 36 4 ,P <0 0 5 ) ,与胎盘重量无相关性 (r =0 1 94 ,P >0 0 5 ) ;脐血IGF Ⅰ水平与新生儿出生体重及胎盘重量呈正相关 (r =0 4 75 ,r =0 4 86 ,P <0 0 5 )。结论　FGR孕妇脐血瘦素水平降低与胎儿脂肪沉积减少有关 ,脐血瘦素水平可作为预测胎儿体重的一项指标。血清与脐血IGF Ⅰ的分泌相对独立 ,提示IGF Ⅰ不能通过胎盘屏障。脐血IGF Ⅰ水平降低 ,可能是导致FGR的病因之一。     

孕妇血清瘦素水平的测定

目的　探讨孕妇血清瘦素水平的变化及其与妊娠的关系。方法　采用放射免疫测定法 ,测定 2 5 1例孕妇 (观察组 )和 35例年龄、体重指数相近的正常非孕妇女 (对照组 )的血清瘦素水平 ,并将瘦素水平与孕妇的孕周、体重、体重指数、腹围、子宫底高度、血压等的关系进行了相关分析。结果　观察组瘦素水平为 (15 .1± 7.4) μg/L ,对照组瘦素水平为 (9.1± 4.9) μg/L ,两组比较 ,差异极有显著性 (P <0 .0 0 1)。相关分析显示 ,孕妇血清瘦素水平与其体重 (r =0 .5 2 9)、体重指数 (r =0 .5 5 1)、腹围 (r=0 .5 6 4)、子宫底高度 (r =0 .15 1)、收缩压 (r =0 .134 )、舒张压 (r=0 .2 5 1)均有相关性。妊娠期间 ,血清瘦素水平虽然逐渐上升 ,但直到孕 30周 ,统计学上尚无明显差异。结论　监测孕妇瘦素水平变化 ,对妊娠并发症 (如妊娠高血压综合征 )的临床观察可能有一定的意义     

血清瘦素及瘦素受体基因Gln223Arg多态性与妊娠期糖尿病的相关性研究

目的:探讨血清瘦素水平及瘦素受体基因Gln223Arg多态性与妊娠期糖尿病的相关性。方法:应用放射免疫分析法(RIA)及聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)技术,检测62例妊娠期糖尿病(GDM)患者及60例正常孕妇(NGT)血清瘦素及瘦素受体基因Gln223Arg多态性。结果:(1)GDM组血清瘦素水平为14.2±4.3μg/L,NGT组为10.1±2.6μg/L,二者差异有统计学意义(P<0.05)。(2)GDM组孕妇瘦素受体基因Gln223Arg基因型GG、(GA+AA)频率分别为61.29%、38.71%,正常孕妇组分别为81.67%、18.33%,两组比较差异有统计学意义(P<0.05);GDM组孕妇瘦素受体基因Gln223Arg等位基因频率G、A分别为77.42%、22.58%,正常孕妇组孕妇分别为89.17%、10.83%,两组比较差异有统计学意义(P<0.05);(3)GDM组中基因型为GA+AA的孕妇瘦素水平为15.3±4.1μg/L,GG基因型为13.5±3.7μg/L,二者差异有统计学意义(P<0.05)。结论:瘦素,瘦素受体基因Gln223Arg多态性与GDM相关,GDM患者瘦素受体基因Gln223Arg变异可能影响血清瘦素水平。     

瘦素和瘦素长受体在胚胎停止发育中的表达

目的:探讨瘦素(Leptin)和瘦素长受体(OB-RL)mRNA及蛋白在胚胎停止发育(胚停育)中的表达及意义。方法:应用RT-PCR检测48例胚胎停育妇女(胚停育组)及30例正常早孕人工流产妇女(对照组)绒毛组织的Leptin、OB-RLmRNA。应用免疫组化技术检测两组妇女绒毛的Leptin和OB-RL蛋白。结果:RT-PCR检测表明,胚停育组Leptin mRNA及OB-RLmRNA表达明显低于对照组,有统计学意义(P<0.01,P<0.01)。免疫组化法检测Leptin及OB-RL蛋白,胚停育组及对照组呈阳性至强阳性表达,胚停育组Leptin、OB-RL蛋白均明显低于对照组(P<0.01)。经两种方法检测,Leptin、OB-RLmRNA和蛋白均明显低于对照组。结论:瘦素在胚胎发育中起重要作用,瘦素和瘦素长受体降低,可能预示胚胎停止发育。     

Characterization of changes in leptin and leptin receptors in a rat model of preeclampsia

OBJECTIVE: The purpose of this study was to determine the influence of reduced uteroplacental perfusion pressure on plasma leptin and placental leptin receptor expression in rats that develop hypertension in the third trimester of pregnancy. STUDY DESIGN: The ovarian arteries and abdominal aortae of pregnant Sprague-Dawley rats (n=9) were constricted surgically on day 14 of gestation and were matched with sham controls. Systolic blood pressure and weight were measured biweekly. Maternal plasma leptin levels, placental leptin receptor abundance, fetal number, fetal weight, and placental weight were determined. RESULTS: Reductions in perfusion pressure induced a significant decrease in maternal plasma leptin. Maternal systolic blood pressure and leptin receptor protein abundance was increased in the experimental group. Litter size and fetal and placental weight were significantly decreased in response to reduced perfusion pressure. CONCLUSION: Reduced uteroplacental perfusion pressure reduces litter size, fetal and placental weights, and maternal plasma leptin levels and increases placental expression of leptin receptors.     

Serum adiponectin, leptin and soluble leptin receptor in pre-eclampsia.

OBJECTIVES: To delineate the changes in serum levels of adiponectin, leptin and soluble leptin receptor, and in the free leptin index in women with pre-eclampsia. METHODS: Blood samples were collected from 38 pregnant women with pre-eclampsia and 42 normotensive pregnant women as controls. Serum concentrations of adiponectin, leptin and soluble leptin receptor were determined by enzyme-link immunosorbent assay and the free leptin index was calculated as the ratio of serum leptin to soluble leptin receptor for each sample. RESULTS: No significant differences were observed between the groups regarding maternal age, gestational age and body mass index. Women with pre-eclampsia had significantly higher levels of serum adiponectin and leptin, and a higher free leptin index than controls (P<0.01, P<0.001 and P<0.001, respectively). There were no significant differences between the two groups in serum levels of soluble leptin receptor (P>0.05). CONCLUSIONS: The study demonstrated elevated serum levels of adiponectin and leptin as well as a higher free leptin index in women with pre-eclampsia, suggesting these as important factors contributing to this complication of pregnancy.     

Serum pattern of circulating free leptin, bound leptin, and soluble leptin receptor in the physiological menstrual cycle

OBJECTIVE: To investigate the serum pattern of free leptin, bound leptin, and soluble leptin receptor throughout the physiological menstrual cycle. DESIGN: Prospective observational study. SETTING: Tertiary care center for gynecological endocrinology and reproductive medicine and a university research laboratory. PATIENT(S): Thirty regularly cycling volunteers (age, 29 +/- 4.2 years). INTERVENTION(S): Blood sampling was performed at different phases (early and mid follicular phase, preovulatory phase, and early and late luteal phase) of three consecutive menstrual cycles; each phase of the menstrual cycle was investigated twice. MAIN OUTCOME MEASURE(S): Free leptin, bound leptin, soluble leptin receptor, LH, E(2), P, vaginal ultrasound. RESULT(S): A peak of serum free leptin levels was found in the late luteal phase followed by a significant drop in the early follicular phase and again by a continuous increase up to the next luteal peak. There were no significant alterations in serum bound leptin and soluble leptin receptor levels. CONCLUSION(S): The present study shows that there are significant circacyclic fluctuations of free leptin levels with the highest concentrations in the late luteal phase and the lowest levels in the early follicular phase, which suggests that circulating free leptin is up-regulated by the C(21)-steroid (P). Circulating bound leptin and soluble leptin receptor are not altered by the cyclic hormone status. The significant rise of the leptin bioequivalent, free leptin, in the late luteal phase might be of importance for the luteal-follicular and the luteal-preimplantatory functional shift.     

Further studies on leptin and leptin receptor expression in myometrium and uterine myomas

AIM: Examination of the potential role of leptin in the development of uterine myomas. Expression of the leptin gene and leptin receptor gene was tested in the myometrium of healthy women, and in myomas and the surrounding myometrium of women with benign tumors. METHODS: Using RT-PCR, expression of the leptin gene and leptin receptor gene were studied in myomas and in the surrounding myometrium in 30 women with uterine myomas at various phases of the menstrual cycle, and in the myometrium of ten women in a control group. Presence of leptin gene proteins and leptin receptor gene proteins in the women was also examined by Western blotting. RESULTS: Using RT-PCR, expression of the leptin gene was demonstrated both in myomas and in the surrounding myometrium. In contrast, expression of the gene could not be detected in the myometrium of healthy women. The results were confirmed by Western blotting, which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues. CONCLUSION: Demonstration of the expression of leptin genes and leptin proteins in uterine myomas and in the surrounding myometrium, and their absence in the myometrium of healthy women suggests the involvement of leptin in the development of uterine myomas.     

Hormonal regulation of neonatal weight: placental leptin and leptin receptors

Objective To examine whether umbilical and maternal leptin levels correlate with birthweight, placental weight, and maternal weight; and to detect membrane-bound leptin receptors in placental tissue as well as soluble leptin receptors in umbilical and maternal blood.
Design Prospective observational study.
Setting University teaching hospital.
Methods Serum levels of leptin and soluble leptin receptors were analysed in 31 randomly selected mother/newborn pairs at delivery. In addition, placental tissue was assayed for leptin receptors using immunocytochemistry and Western blot.
Results The mean [SD] leptin level in umbilical cord venous blood (7.1 ng/mL [4.0]) was significantly lower (   P < 0.001  ) than in maternal blood (22.5 ng/mL [10.8]). Umbilical cord leptin concentrations correlated significantly with birthweight (   P < 0.001  ), placental weight (   P < 0.005  ) but not with maternal leptin. Maternal leptin concentrations correlated only with maternal weight (   P < 0.001  ). In chorionic villous tissue, trophoblasts stained strongly positive for leptin receptor-like immunoreactivity. Two membrane-bound isoforms of the leptin receptor were also detected in placental tissue. In both umbilical and maternal serum, a soluble leptin receptor was found migrating as broad band at M_r 97,000 D.
Conclusion The present data strongly reinforce the idea that circulating leptin levels may provide a growth-promoting signal for fetal development during late pregnancy. While membrane-bound leptin receptors may be involved in autocrine regulation of placental leptin production, the soluble receptor form may serve as a transport vehicle for leptin to fetal tissues.     

瘦素在胎盘组织中的表达及其与新生儿体重的关系

目的探讨瘦素在胎盘组织中的表达及其与新生儿体重的关系.方法采用放射免疫法(RIA)检测100例足月孕妇静脉血及其新生儿脐血瘦素水平,根据新生儿出生体重分为大于胎龄儿(LGA)组19例,适于胎龄儿(AGA)组65例,小于胎龄儿(SGA)组16例,同时采用逆转录-聚合酶链反应(RT-PCR)技术,检测41例胎盘组织中瘦素mRNA表达水平.结果(1)胎盘组织中瘦素mRNA表达水平为0.97±0.04,与新生儿体重呈显著正相关关系(r=0.43,P＜0.01).其中LGA组(1.01±0.03)显著高于AGA组(0.97±0.02),SGA组(0.93±0.03)显著低于AGA组,差异均有极显著性(P＜0.01).(2)母血瘦素水平为(14.22±7.66)μg/L,与新生儿体重无相关关系(r=0.11,P＞0.05).(3)新生儿脐血瘦素水平为(7.58±5.15)μg/L,与新生儿体重呈显著正相关关系(r=0.57,P＜0.01),其中LGA组脐血瘦素水平为(13.38±6.75)μg/L,显著高于AGA组的(7.40±4.45)μg/L,SGA组为(2.79±1.54)μg/L,显著低于AGA组,差异有极显著性(P＜0.01).结论脐血及胎盘组织中瘦素水平与胎儿生长发育状态密切相关;母血瘦素水平与新生儿体重无关;孕期胎儿瘦素的重要来源是胎盘组织.