瘦素、瘦素受体与肝纤维化的研究进展

瘦素(leptin)为肥胖基因(ob)的产物,这种脂肪来源的激素已被证明有多种生理学效应,其效应通过细胞因子样受体介导。近年的研究证实它与肝纤维化的发生发展亦有着密切的关系。本综述描述了瘦素及其受体与肝纤维化的关系及其在肝纤维化发病机制中的作用的最新进展。     

瘦素水平与妊娠的关系(综述)

近年来,国内外学者通过对妊娠期患有糖代谢异常、妊娠高血压疾病孕妇体内血清瘦素水平的测定及胎儿羊水、脐血中瘦素水平的测定发现,瘦素与糖代谢异常、妊娠高血压疾病及胎儿生长发育有密切关系。一、瘦素与妊娠糖代谢异常的关系妊娠期糖代谢异常包括妊娠期糖尿病和妊娠期     

瘦素及瘦素受体基因多态性与乳腺癌的相关性研究

目的探讨瘦素及其瘦素受体基因多态性与乳腺癌发生的关系。方法采用PCR- RFLP对94例乳腺癌患者、128例健康对照者进行瘦素受体基因Gln223Arg多态性检测;ELISA分析法测定瘦素水平。结果乳腺癌组瘦素受体基因Gln223Arg的GG、GA和AA基因型表达频率分别为69.15%、17.02%和13.83%;等位基因G和A为77.66%和22.34%与对照组82.03%、15.63%和2.34%及等位基因的89.84%和10.16%相比较,差异有统计学意义(P=0.004,P=0.001)。乳腺癌组瘦素水平,腰臀比(WHR)明显高于对照组,差异均有统计学意义(P<0.01,P<0.001)。非条件logislic回归多因素分析表明,瘦素受体基因多态性、瘦素水平及WHR升高,与乳腺癌发生的相关危险度分别为:OR=4.87,95%CI:1.30-18.22,P=0.019;OR=1.53,95%CI:1.13-2.07,P= 0.006;OR=3.68,95%CI:1.34-10.11,P=0.011。结论瘦素受体基因Gln223Arg多态性、瘦素及WHR升高,可能增加乳腺癌发生的风险性。     

多胎妊娠孕妇脐血瘦素水平与胎儿体重相关性的研究

目的研究多胎妊娠孕妇的母血、脐血瘦素水平及其与新生儿体重的关系与单胎妊娠孕妇有无不同。方法对本院住院分娩的正常多胎妊娠孕妇42例,同孕龄单胎妊娠孕妇20例,分别于分娩前抽取肘前静脉血,分娩时抽取脐静脉血测定瘦素水平。结果多胎妊娠孕妇母血瘦素水平、脐血瘦素水平及新生儿体重与正常同孕龄单胎妊娠妇女比较差异无统计学意义。2组孕妇脐血瘦素水平与新生儿体重均呈正相关,多胎妊娠组(r=0.76,t=10.86,P<0.01),单胎妊娠组(r=0.81,t=5.86,P<0.01)。结论妊娠胎数对母血、脐血瘦素水平并无影响,脐血瘦素水平同样可以反应多胎妊娠的胎儿宫内生长情况。     

瘦素与胎儿生长发育的关系及研究进展

瘦素是新近发现的、脂肪组织合成分泌的激素,因其在实验动物饮食行为、能量代谢和生殖发育中起关键调节作用而日益受到关注.近年来研究发现瘦素不仅可调节体内的能量代谢和脂肪沉积,且与胎儿生长发育有着密切的关系.瘦素可调控胎儿体重的增长,在胎儿生长发育中起着重要的作用,成为近年来的研究热点之一.胎儿瘦素究竟来源于胎儿自身组织还是胎盘颇有争议.胎儿瘦素可受激素、性别、母亲因素、遗传因素等影响.该文将就瘦素与胎儿生长发育的关系及研究进展作以综述.     

肥胖儿童运动习惯与瘦素,瘦素受体的关系

目的 了解超重及肥胖儿童运动习惯以及与瘦素,瘦素受体的关系.方法 研究对象为超重或肥胖小学生67名,其中男生33名,女生34名,年龄8～12岁.研究对象的运动数据使用能量检测仪收集,取两周的平均值;瘦素和瘦素受体采用酶联免疫吸附试验检测法测定.结果 被调查儿童中男生体重指数高于女生,而瘦素水平女生高于男生.平日运动总量,有效运动量,有效运动时间与有效运动次数男生均高于女生.男女生瘦素与平日运动数据之间均为负相关,但男生无统计学意义,而女生P值均小于0.01.瘦素受体与运动数据的相关关系均无统计学意义.结论 建议通过增加运动量改善超重或肥胖.     

瘦素、可溶性瘦素受体与多囊卵巢综合征

瘦素(leptin)是肥胖基因编码的一种脂肪源性肽类激素,以游离型和结合型两种形式存在于血循环中,仅游离瘦素有生物学活性,在调节能量平衡和正常生殖功能中起重要作用,可溶性瘦素受体(sOB-R)是决定游离瘦素水平的主要结合蛋白.目前研究发现,多囊卵巢综合征(PCOS)患者多存在血清sOB-R水平和游离瘦素水平异常,可能参予了PCOS患者瘦素抵抗、肥胖及性激素代谢紊乱的形成,就瘦素、sOB-R与PCOS胰岛素抵抗、瘦素抵抗及代谢异常的关系做一综述,探讨其在PCOS发病中的作用.     

瘦素、可溶性瘦素受体与多囊卵巢综合征

瘦素(leptin)是肥胖基因编码的一种脂肪源性肽类激素,以游离型和结合型两种形式存在于血循环中,仅游离瘦素有生物学活性,在调节能量平衡和正常生殖功能中起重要作用,可溶性瘦素受体(sOB-R)是决定游离瘦素水平的主要结合蛋白。目前研究发现,多囊卵巢综合征(PCOS)患者多存在血清sOB-R水平和游离瘦素水平异常,可能参予了PCOS患者瘦素抵抗、肥胖及性激素代谢紊乱的形成,就瘦素、sOB-R与PCOS胰岛素抵抗、瘦素抵抗及代谢异常的关系做一综述,探讨其在PCOS发病中的作用。     

超重及肥胖儿童运动习惯与瘦素及其瘦素受体的关系

目的 了解嘉兴市超重及肥胖儿童运动习惯以及与瘦素、瘦素受体的关系.方法 选取嘉兴市超重或肥胖的67名小学生,其中男生33名,女生34名,年龄8 ～12岁.研究对象的运动数据使用能量检测仪收集,取2周的平均值;瘦素和瘦素受体采用酶联免疫吸附试验检测法测定.结果 被调查儿童中男生体质指数高于女生,而瘦素水平女生高于男生.平日运动总量,有效运动量,有效运动时间与有效运动次数男生均高于女生.男女生瘦素与平日运动数据之间均为负相关,但男生无统计学意义,而女生有统计学意义(P均小于0.01).瘦素受体与运动数据的相关关系均无统计学意义.结论 增加运动量,提高瘦素敏感度为今后研究和探索改善儿童超重或肥胖的方法之一.     

瘦素和瘦素受体在子宫内膜异位症患者在位内膜和异位内膜的表达

目的通过测定瘦素(leptin)和瘦素受体(leptin receptor,Ob-R)在卵巢子宫内膜异位症(endometriosis,EMs)患者异位内膜及在位内膜中的表达,探讨瘦素系统在子宫内膜异位症发生发展中的作用及意义。方法收集2008年7月至11月,在本院因卵巢子宫内膜异位症行腹腔镜手术的25例患者的异位内膜和在位内膜为研究对象,分别纳入A组和B组。收集同期在本院因子宫肌瘤行腹腔镜手术的24例患者的正常内膜组织,纳入对照组。对研究组和对照组患者的子宫内膜组织,分别采用免疫组化SP法检测瘦素和瘦素受体水平(本研究遵循的程序符合本院人体试验委员会所制定的伦理学标准,得到该委员会批准,分组征得受试对象本人的知情同意,并与之签署临床研究知情同意书)。A,B组和对照组患者年龄、体重指数(body mass index,BMI)、末次月经及内膜组织学Noyes分期等比较,差异无显著意义(P>0.05)。结果瘦素和瘦素受体在B组、A组和对照组子宫内膜腺体及间质内,均可见阳性表达。瘦素在A组腺体的表达,明显高于间质,且差异有显著意义(P<0.05)。瘦素在A组、B组和对照组的表达比较,差异无显著意义(P>0.05),但瘦素在A组间质的表达,低于对照组和B组,且差异有显著意义(P<0.05)。瘦素受体在A组腺体和间质的表达比较,差异无显著意义(P>0.05);瘦素受体在A组腺体的表达,低于B组和对照组,差异有显著意义(P<0.05);而其表达在间质比较,则差别无显著意义(P>0.05)。瘦素在B组增生期腺体和间质的表达,高于分泌期,但差异无显著意义(P>0.05);而瘦素在对照组增生期腺体和间质的表达,高于分泌期,且差异有显著意义(P<0.05);瘦素受体在B组和对照组增生期和分泌期表达比较,差异均无显著意义(P>0.05,P>0.05)。结论瘦素和瘦素受体在卵巢内膜异位症异位内膜中的低表达,表明瘦素系统在卵巢异位病灶发展过程中的作用有限。     

慢性肾功能衰竭大鼠瘦素、神经肽Y及其受体的基因表达

目的 探讨瘦素、神经肽Y及其受体在慢性肾功能不全中的变化及意义。方法 将40例Wistar大鼠随机分为正常对照组(n=15)和慢性肾功能不全组(n=25)，采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学技术检测脂肪组织瘦素和脑组织瘦素受体(Oh-Ra、0h-Rh)及神经肽Y(NPY)的基因及蛋白表达。结果 慢性肾功能不全大鼠脂肪组织瘦素基因表达降低而蛋白表达增强，脑组织可见Oh-Ra和Oh-Rh的表达增强及NPY的表达降低。结论 慢性肾功能不全大鼠存在明显的NPY、瘦素及其受体的代谢紊乱，过量的瘦素有可能通过增强受体的活性而增加下丘脑的转运及其信号传导，从而抑制NPY的表达．     

Leptin and leptin-receptor polymorphisms in fertile and infertile men

The association of leptin (LEP) -2548G/A and/or leptin receptor (LEPR) Gln223Arg polymorphisms with male infertility and plasma FSH, LH, and testosterone (T) levels was examined. The genotypes and allele frequency distributions of LEP -2548G/A and LEPR Gln223Arg polymorphisms were investigated in 150 fertile and 150 infertile men by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Also, plasma levels of FSH, LH, and T were measured using commercial ELISA kits. Frequencies of AA, AG and GG genotypes of LEP-2548G/A polymorphism were statistically different in fertile and infertile men (p=0.012). The AG genotype showed a protective effect which could decrease risk of male infertility about 3 fold (p = 0.004). We did not observe any differences in frequencies of LEPR Gln223Arg alleles and genotypes between groups (p > 0.05). Sperm counts from infertile men with the AG and GG genotypes of the LEP polymorphism were significantly higher than AA genotype (p<0.05). Moreover, infertile men who carried the RR genotype of LEPR showed a statistically higher percentage of sperm with progressive motility than individuals with other genotypes (p = 0.004). There was no correlation between different combinations of LEP and LEPR genotypes and LH, FSH, and T levels (p > 0.05). Our study suggests that the LEP -2548G/A polymorphism may play a role in male fertility and the AG genotype may have a protective effect through increasing sperm counts. The distribution of genotypes of LEP -2548G/A polymorphism are different in fertile and infertile males and may be a useful tool in evaluation of male infertility.

Abbreviations: LEP: leptin; LEPR: leptin receptor; T: testosterone; FSH: follicle-stimulating hormone; LH: luteinizing hormone     

血清瘦素、血脂水平与妊娠期高血压疾病的关系

目的探讨血清瘦素（leptin）、血脂（serum lipid）在妊娠期高血压疾病（hypertensive disor dercomplicating pregnancy）发病中的意义及相互关系。方法选取2006年7月至2007年2月在山西省临汾市人民医院妇产科住院待产的20例妊娠期高血压、27例子痫前期及同期正常晚期孕妇30例为研究对象。将其分为妊娠期高血压组（A组,n=20）,子痫前期组（B组,n=27）,正常妊娠组（C组,n=30）（本研究遵循的程序符合山西省临汾市人民医院人体试验委员会所制定的伦理学标准,得到该委员会批准,取得受试对象的知情同意,并签署临床研究知情同意书）。采用放射免疫法测定血清瘦素水平,分别采用COD-PAP法和GPO-PAP法,测定血清总胆固醇（total cholesterol,TC）、甘油三酯（triglyceride,TG）。结果①单因素方差分析表明,三组孕妇母血清中瘦素、总胆固醇、甘油三酯水平上比较,差异有显著意义（P〈0．01）;②血清瘦素水平与血清中总胆固醇、甘油三酯的相关性分析结果表明,A组及C组血清瘦素水平与总胆固醇、甘油三酯呈正相关,而B组血清瘦素水平与总胆固醇呈正相关,与甘油三酯无明显相关性。③血清瘦素水平与孕晚期孕妇体重指数（body mass index,BMI）呈正相关,而C组相关性更显著;血清瘦素水平与收缩压（systolic blood pressure,SBP）、舒张压（diastolic blood pressure,DBP）呈正相关,而C组相关性更显著。结论正常妊娠母体血清瘦素水平与自身体脂积累密切相关。妊娠期高血压疾病患者母血清总胆固醇与血清瘦素水平呈正相关,两者共同参与妊娠期高血压疾病发病。母血清瘦素水平有望成为妊娠期高血压疾病的观察指标之一。     

Leptin and Reproduction

Leptin, a hormone secreted from adipose tissue, plays an important role in reproductive physiology. It has been shown to stimulate the reproductive system by rescuing the sterility of leptindeficient mice and advancing the onset of puberty in normal mice. Although leptin is not critical for the biology of pregnancy in mice, its ability to reduce food intake is blunted in midgestation suggesting that late pregnancy may be a leptin-resistant state. Modifier genes originating from the Balb/cJ genetic background profoundly alter the sterile-obese phenotype of ob/ob mice by reducing their obesity and stimulating their reproductive system despite the absence of leptin. The mechanism of leptin's action on the reproductive system remains to be determined but is likely to be mediated by multiple factors.     

妊娠期高血压疾病患者尿瘦素水平的测定与分析

目的探讨妊娠高血压疾病（hypertensivedisordercomplicatingpregnancy,HDCP）患者尿瘦素（urinaryleptin）水平变化及其与妊娠高血压疾病的临床关系。方法选择2005年5月至2007年12月在广西中医学院第一附属医院住院的自愿参加本研究的90例孕妇为研究对象,将其按有无妊娠高血压疾病分为HDCP组（n=40）和对照组（n=50）。再将HDCP组分为,妊娠期高血压组（n=11）,轻度子痫前期组（n=16）,重度子痫前期组（n=13）（本研究遵循的程序符合广西中医学院第一附属医院人体试验委员会所制定的伦理学标准,得到该委员会批准,分组取得受试对象的知情同意,并与其签署临床研究知情同意书）。采用酶联免疫吸附测定（enzymelinkedimmunosorhentassay,ELISA）法分别测定两组孕妇尿瘦素水平,并行相关分析。结果HDCP组孕妇尿瘦素水平[（0．93±0．46）ng／mL]较对照组[（0．62±0．39）ng／mL]高,两组比较,差异有显著意义（P〈0．05）。HDCP组中,妊娠高血压组、轻度子痫前期组患者尿瘦素水平分别与对照组比较[（0．76±0．36）ng／mL与（0．81±0．45）ng／mLvs．（0．62±0．39）ng／mL2,差异无显著意义（P〉0．05）,但均明显低于重度子痫前期组[（1．21±0．52）ng／mL]。尿瘦素水平与妊娠高血压疾病患者的尿蛋白量相关,而与患者体重指数（bodymassindex,BMI）、收缩压与舒张压等临床参数无关。结论妊娠期尿瘦素水平增高,可能与妊娠高血压疾病对肾功能影响有关。尿瘦素水平的测定,对判断妊娠高血压疾病的严重程度具一定临床价值。     

孕妇哮喘及其安全监护

通过综述孕妇哮喘的机体特殊性,指导临床对其治疗及其安全监护。对妊娠期母体与胎儿肺生理学特点、妊娠期呼吸系统的变化、哮喘与妊娠互为影响的呼吸功能状况及其治疗原则进行分析。妊娠哮喘对胎儿有一定影响,密切监测胎儿的状况极为重要。哮喘与妊娠的免疫反应呈双向性相互影响。     

High Maternal Omega-3 Supplementation Dysregulates Body Weight and Leptin in Newborn Male and Female Rats: Implications for Hypothalamic Developmental Programming

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-pregnancy will have disrupted metabolic outcomes. We also determined if these HFSD-related effects could be reversed by a shift to a healthier diet post-conception, in particular to a diet high in omega-3 polyunsaturated fatty acids (ω3 PUFAs), since ω3 PUFAs are considered essential for normal neurodevelopment. Unexpectedly, our data show that there are minimal negative effects of maternal HFSD on newborn pups. On the other hand, consumption of an ω3-replete diet during pregnancy altered several developmental parameters. As such, pups born to high-ω3-fed dams weighed less for their length, had reduced circulating leptin, and also displayed sex-specific disruption in the expression of hypothalamic neuropeptides. Collectively, our study shows that maternal intake of a diet rich in ω3 PUFAs during pregnancy may be detrimental for some metabolic developmental outcomes in the offspring. These data indicate the importance of a balanced dietary intake in pregnancy and highlight the need for further research into the impact of maternal ω3 intake on offspring development and long-term health.     

The early relationship of mother and pre-infant: Merleau-Ponty and pregnancy

Abstract This paper critically evaluates current conceptions of pregnancy as a possession of either mother or infant. In opposition to the more common stance that marks birth as the beginning of intercorporeality and perception, pregnancy is instead phenomenologically delineated as a chiasmic relationship between mother and her pre‐infant from a Merleau‐Pontian perspective. This paper maintains that during pregnancy a mother‐to‐be and her pre‐infant are deepened and modified through their intertwining.     

Pregnancy Is Enough to Provoke Deleterious Effects in Descendants of Fructose-Fed Mothers and Their Fetuses

The role of fructose in the global obesity and metabolic syndrome epidemic is widely recognized. However, its consumption is allowed during pregnancy. We have previously demonstrated that maternal fructose intake in rats induces detrimental effects in fetuses. However, these effects only appeared in adult descendants after a re-exposure to fructose. Pregnancy is a physiological state that leads to profound changes in metabolism and hormone response. Therefore, we wanted to establish if pregnancy in the progeny of fructose-fed mothers was also able to provoke an unhealthy situation. Pregnant rats from fructose-fed mothers (10% w/v) subjected (FF) or not (FC) to a fructose supplementation were studied and compared to pregnant control rats (CC). An OGTT was performed on the 20th day of gestation, and they were sacrificed on the 21st day. Plasma and tissues from mothers and fetuses were analyzed. Although FF mothers showed higher AUC insulin values after OGTT in comparison to FC and CC rats, ISI was lower and leptinemia was higher in FC and FF rats than in the CC group. Accordingly, lipid accretion was observed both in liver and placenta in the FC and FF groups. Interestingly, fetuses from FC and FF mothers also showed the same profile observed in their mothers on lipid accumulation, leptinemia, and ISI. Moreover, hepatic lipid peroxidation was even more augmented in fetuses from FC dams than those of FF mothers. Maternal fructose intake produces in female progeny changes that alter their own pregnancy, leading to deleterious effects in their fetuses.