【作者】 李剑；

【导师】 潘长玉； 陆菊明；

【作者基本信息】 军医进修学院 ， 糖尿病防治， 2001， 博士

【摘要】 一．人血清瘦素的放射免疫分析 研究目的 建立人血清瘦素的放射免疫分析（RIA）方法。研究对象 和方法 27例男性和24例女性75gOGTT正常受试者。RIA中应用兔抗人 瘦素抗血清。结果 l标准曲线范围0．5-24ng/ml，精密度 批内变异系 数（CV）2 94%－4 63％，批间CV 3 83％－5 64%。准确性 回吸收率 （％）90 65%-93 53％。稀释试验回吸收率 93 46％一98 88%.特异性 与白细胞介素（IL）－1、IL－2、IL－3、IL－6、IL－8、肿瘤坏死因子α（TNF－ α）, 集落细胞刺激因子（GM-CS）等无交又反应。敏感性 可测最低值 为0 45 ng／ml。与其它方法比较 与人瘦素IRMA试剂盒（DSL 23100） 的比较 相关系数r=0 98，p＜0 01。2人血清瘦素的初步测定及其影响 因 素．男 性的血清瘦素浓度 [Median（25，75%）] 平 均 为 4 51（3 29，5 23）ng／ml，女性为7 43（5 26，9 99）ng／ml，女性高于男性， Z＝3 878，p＜0 01。3 经 Spearman相关分析，在男性，空腹血清瘦素与 BMI的相关性为 r＝0 516，p＝0 01，与空腹胰岛素的相关性为 r＝0 3 6 2， p＜0 05。在女性 空腹血清瘦素与BMI的相关性为r=0 442，p＜0 01。 二 人类血清瘦素水平及其影响因素的研究 分析性别、体重、不同葡萄糖耐量程度以及胰岛素对人类血清瘦素 水平的影响。分两部分 （一）不同葡萄糖耐量状态下人的血清瘦素水平及其影响因素 研究目的·探讨不同葡萄糖耐量程度时血清瘦素等代谢指标的水平 以及血清瘦素水平的相关因素。研究对象和方法：218例受试者，男107 3 解放军总医院 博士学位论文 军医进修学院 中文摘要 例，女 111例；分为 NGT组（104例）、IGT组（76例）、DM组（38例）。 其中非肥胖男性71例、女性77例，肥胖男性％例、女性34例。分别 按照性别、肥胖以及不同葡萄糖耐量程度分组，观察性别、体重（wT）、 BM、腰臀匕（W H）、血压、FBS、CH、TG、HDL、LDL、瘦素、空腹胰岛 素、胰岛素抵抗指数（IR）在各组间的差异。并且用 Spear。an相关分析 和逐步回归分析确定血清瘦素的影响困素。结果：NGT的非肥胖男性的 血肴瘦素LMedlan（25，75％）］为 4 50（3 26，5 19）ng／ml，女性为 7 24 （5 04，8 99）ng／ml，P＜0 01。NGT 的男性肥胖者的血清瘦素为 5 50（4 46，8 78）ng／ml，非月巴胖者为 4 50（3 26，5 19）ng／ml，p＜0 01． NGT的女性R巴胖者的血清瘦素为 9 85（8 87，13 12）ng／ml，非8巴胖者为 7 24（5 04，8 99） ng／ml，P＜0．01。非肥胖男性 NGT、IGT、DM组的瘦素 分别为 4 50（3 26，5 19）、4 66（3 49，5 20）、5 46（4 44，7 07）ng／ml， P一0．109，在女性则分别为 7 24（5 04，8 99）、7 81（5 15，10 22）、11 03 （7 07，14 34）ng／ml，P＜0 05。在男性 WT、BMI、腰围（WC）、臀围（HC）、 W／H、FBS、Inso和IR与空腹血清瘦素呈正相关（p＜0 05）。在女性WT、 BMI、WC、HC、TG、CH、Inso和IR与窒腹血清瘦素正相关。经逐步回 归分析，在男性删I、h s O，在女性删I、hso、TG是血清瘦素水平的 独立影响因素（P＜0 05）。 （二）短效胰岛素单剂量皮下注射对血清瘦素的影响 研究目的：短效胰岛素单次皮下庄射后血清胰岛素水平变化对血清 瘦素的影响。研究对象和方法11名健康成年男性志愿者。g腹禁食状 态，以Ou从g剂量单次皮下庄射优泌林R，观察胰岛素注射前3o分 及注射后 30、60、90分钟和 2、4、6、8。J、时 8个点血清瘦素和胰岛素 动态水平。结果·庄射胰岛素后血清胰岛素快速升高，但是血清瘦素水 平无显著变化。经回归分析 r‘刊 045，p司．sl，血清瘦素水平与皮下 庄射胰岛素后的变化无相关性。 4 ?更多还原

【Abstract】 1.Establishment of Human Serum Leptin RadioimmunoassayAIM:To establish human serum leptin RIA MATERAILS ANDMETHODS:The rabbit anti-human leptin antibody was used in the RIA of leptin 27 males and 24 females with normal 75gOGTT were included in the study RESULTS: 1.The leptin determinable range of this method was 0 5-24 ng /ml The CV of intra-assay and inter-assay were 2 94%-4 63% and 3 83%-5 64%, respectively The lowest determinable level of leptin was 0 45 ng/ml The rate of reabsorption was 90 65%-93 53%, the rate of reabsorption in dilution test was 93 46%-98 88% No cross-reaction was found with interleukin (IL)-1,2,3,6,8, tumor necrosis factor-a and GM-CS in this RIA The values of serum leptin measured by this method were similar to IRMA kit(DSL23100), r=0 98, p<0 01 2. The serum leptin[Median(25,75%)]level was 4 51(3 29,5 23)ng/ml in 27 men, and was 7 43(5 26, 9 99) ng/ml in 24 women, Z=3 878, p<0 01 3.Spearman analysis showed the fasting leptin was correlated with BMI and fasting insulin in men, and with BMI in women2 Human Serum Leptin Level and Its Related FactorsThe effect of sex, body weight, insulin and different glucose tolerance on human serum leptin was analyzed(1)The Serum Leptin Level and Its Related Factors in the Subjectsi1~~with Different Glucose ToleranceAIM:To study the serum leptin levels in different glucose tolerance subjects and its related factors SUBJECTS AND METHODS: 218 subjects were divided into 3 groups according to their 75g OGTT 104 were NGT, 76 were IGT, 28 were DM Among them 71 males and 77 females were non-obese, 36 males and 34 females were obese. The body weight, BMI, waist to hip ratio, blood pressure, FBS, CH, TG , HDL, lept in, fasting insulin and HOMA IR were measured in all subjects RESULTS3 The serum leptin[Median(25,75%)lwas 4 50(3 26,5 19)ng/ml in non-obese NGT men,7 24(5 04,8 99)ng/ml in non-obesewomen, p<0 01 The serum leptinwas5 50(4 46,8 78)ng/ml in obese NGT men, 4 50(3 26,5 19)ng/ml in non-obese men, p<0 01 The serum leptin was 9 85(8 87, 13 12) ng/ml in obese NGT women, 7 24(5 04,8 99) ng/ml in non-obese women, p<0 01 The serum leptin was 4.50(3 26,5 19),4 66(3 49,5 20),5 46(444,7 07)ng/ml inNGT, IGT, DM of non-obese men(p0 109) In non-obese women, the leptin was 7 24(5 04,8 99), 781(5 15,10 22), 11 03 (7 07,14 34)ng/ml, p<0 05 In men, fasting leptin was positively correlated with weight(WT), BMI, waist circumstance (WC), hip circumstance (HC), W/H, FBS, InsO and IR In women, fasting leptin was positively correlated with WT, BMI, IYC, HC, TG, CH, InsO and IR By stepwise regressionanalysis, theBMI, Ins0inmen, andBMI, InsO, TGinwomen were the independent affecting factors of serum leptin.(2)The Effect of Single-dosage Subcutaneous Injection of Insulin on Serum LeptinSAIM:To investigate the effect of single-dosage insulin injection subcutaneously on serum leptin SUBJECTS ANDMETHODS:Single-dosage of regular human insulin was injected subcutaneously in 11 healthy male volunteers The serum insulin and leptin concentrations were analyzed before and 30,60,90 minutes, 2, 4, 6, 8 hours after injection of insulin RESULTS: The serum insulin levels were significantly increased after injection of insulin, while the serum leptin levels were not changed remarkably, r20 045, p-0 513.The Effect of Genetic Factors on Serum Leptin levels and the other Metabolism Items in Subjects with Different Glucose ToleranceAIM:To study the effect of polymorphisms of the genes in relation to leptin signal action SUBJECTS AND METHODS: The subjects studied were as same as that in part2(1) The polymorphisms of OBRb (Gln223Arg), P i-AR (Trp64Arg )and PPARY2 (161 C→T) by PCR-RFLP were analyzed The leptin, BMI, WH, SBP, DBP, PBS, HDL, LDL, CH, TG, insulin and JR were compared between alleles carriers in different glucose tolerance groups RESULTS: 1. In males, Gln223 carriers of OBRb had higher WN/H in NGT, IGT and DM, higher SBP in IGT and DM, and higher DBP in DM CH was higher in IGT and更多还原