糖尿病大鼠血清瘦素与肾脏瘦素受体表达观察

目的研究2型糖尿病大鼠血清瘦素（leptin）及肾脏瘦素受体（Ob-R）表达变化。方法高糖高脂饮食结合小剂量链脲佐菌素建立2型糖尿病大鼠动物模型。在8周末测量大鼠体质量、血压、空腹血糖、三酰甘油、胆固醇和24h尿蛋白排泄量等指标，用酶联免疫吸附法测定大鼠的血清瘦素、胰岛素，计算胰岛素抵抗指数。免疫组化检测Ob-R在肾脏的表达情况。结果糖尿病大鼠体质量、血糖、总胆固醇、三酰甘油、血清胰岛素较对照组均明显升高，24h尿蛋白排泄量轻度升高。与对照组比较，大鼠血清瘦素明显升高，同时糖尿病组肾脏Ob—R的表达水平下降，二者呈负相关。结论2型糖尿病大鼠高血清瘦素可能对肾脏0b-R表达有抑制作用。     

维持血液透析患者血清瘦素水平与代谢性酸中毒的关系及相关因素分析

目的:观察维持血液透析(HD)患者在纠正代谢性酸中毒后血清瘦素(Leptin)浓度及一些营养指标的变化.方法:用酶联免疫吸附(ELISA)方法,测定40例HD前血清Leptin浓度,对其中20例血气分析提示代谢性酸中毒的HD患者,予口服碳酸氢钠,比较治疗前后血清Leptin浓度变化,将Leptin与体重指数(BMI)、血清碳酸氢盐、血浆胰岛素、血浆全段甲状旁腺素(iPTH)及其他生化指标作相关分析.设对照组和健康对照组,各组均以性别再分组.结果:HD患者血清Leptin男组(5.987±5.708)μg/L,与BMI正相关(P＜0.05),女组(8.081±4.524)μg/L,与BMI无相关性.酸中毒组治疗后Leptin、胰岛素略升,血脂代谢也有一定程度的改善,但无统计学差异(P＞0.05).酸中毒的HD患者血清Leptin与碳酸氢盐、胰岛素、iPTH、白蛋白、血脂等均无相关性.男、女两组Leptin均与健康对照组和无酸中毒组比较无统计学差异(P＞0.05).结论:纠正代谢性酸中毒后HD患者营养状况有所改善,血清瘦素浓度无显著变化.     

穴位埋线疗法治疗单纯性肥胖症远期疗效观察

目的：观察穴位埋线疗法治疗单纯性肥胖症的远期疗效。方法：以辨证论治选穴,穴位埋线治疗3个疗程,前后自身对照观察,每次选6～10个穴位。结果：96例患者治疗后体重、体围、皮脂厚度、BMI、F%、WHR、瘦素（Leptin）、Ins、TG、TC、FBS等指标都有不同程度的降低,治疗前后比较,经统计学分析,差异均有显著意义（P〈0.05）。结论：该疗法具有疗效高、方便、安全、无痛苦、持续作用长、无副作用等特点,提示穴位埋线疗法治疗单纯性肥胖症具有减重、降脂、重塑体形和良好的远期疗效。     

肾衰养真胶囊对胰岛素刺激的大鼠脂肪细胞瘦素表达的影响

目的：观察肾衰养真胶囊对胰岛素刺激的大鼠脂肪细胞瘦素（Leptin）分泌及其mRNA表达的影响。方法：给予大鼠灌胃制备肾衰养真胶囊含药血清及阳性对照开同含药血清，应用含药血清处理经胰岛素刺激的脂肪细胞，然后应用放免法检测上清Leptin分泌水平，RT-PCR法检测细胞LeptinmRNA表达水平。结果：经胰岛素刺激后脂肪细胞Leptin表达显著增加，加入肾衰养真胶囊含药血清后脂肪细胞Leptin的表达显著受到抑制。结论：肾衰养真胶囊可抑制胰岛素刺激引起的Leptin的过度表达。     

瘦素/阿片促黑素细胞皮质素原/神经肽Y信号在胃转流术治疗2型糖尿病中的作用

目的 探讨瘦素(Leptin)、神经肽Y(NPY)、阿片促黑素细胞皮质素原(POMC)信号通路在胃转流手术治疗2型糖尿病中的作用及机制.方法采用20只成年SD雄性大鼠成功建立2型糖尿病大鼠模型,随机分为糖尿病非手术对照组(NO组,n=10)和糖尿病手术组[Roux-en-Y胃旁路术(RYGB)组,n=10],另外再选10只正常大鼠作为正常对照组(NC组),对手术组实施胃转流手术,分别于术前、术后检测各组大鼠血糖(GLU)、总胆固醇(TCH)及甘油三酯(TG)、Leptin水平,每天定时监测大鼠饮水量、饮食量以及体质量的变化,术后第4周取大鼠下丘脑,检测下丘脑中NPY、POMC mRNA的表达水平.结果术后第4周,RYGB组大鼠血糖、血脂以及进食、水量已接近正常水平,Leptin和NPY mRNA水平分别由术前的(4.58±0.37)μg/L、1.89 ±0.24降低到(3.10±0.38) μg/L、0.95±0.19(P＜0.01),而POMC mRNA水平则由术前的0.78±0.26升高至1.70±0.31(P＜0.01).结论 胃转流手术可以改善2型糖尿病的血糖水平,Leptin可能通过NPY、POMC神经元信号调节2型糖尿病的能量代谢平衡,提示Leptin与下丘脑NPY、POMC调节通路可能在胃转流手术后2型糖尿病病情缓解过程中发挥重要作用.     

瘦素对血脂及胆汁成分的调节在胆囊胆固醇结石形成中的作用

目的:分析胆囊胆固醇结石患者瘦素与血脂及胆囊内胆汁成分的关系,探讨瘦素在胆囊胆固醇结石形成中的作用。方法:选择胆囊胆固醇结石接受腹腔镜胆囊切除术的患者30例(结石组)与同期因胆囊息肉行腹腔镜胆囊切除术的患者22例(息肉组),检测患者血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、瘦素、胆囊胆汁中的TC与总胆汁酸(TBA)水平,以及胆囊壁组织瘦素受体mRNA水平。结果:与息肉组比较,结石组血清TC、TG、LDL、瘦素水平以及胆囊内胆汁TC/TBA含量比率与胆囊组织瘦素受体mRNA水平均明显升高,而血清HDL明显降低(均P0.05)。结石组的血清瘦素水平与血清TG、TC及胆汁TC均呈正相关(r=0.633,P=0.002;r=0.224,P=0.025;r=0.384,P=0.000),与HDL和TBA呈负相关(r=-0.205,P=0.014;r=-0.548,P=0.024)呈负相关,而息肉组血清瘦素与以上指标间均无关(均P0.05)。结论:瘦素参与了胆囊胆固醇结石的形成,瘦素及其受体水平的升高可能与胆囊胆固醇结石患者胆固醇代谢异常、胆囊胆汁成分失调密切相关。     

瘦素、结合蛋白相互作用对男性生殖调控研究进展

瘦素(Leptin)是肥胖基因(obese gene,obgene)的蛋白产物,主要由脂肪组织分泌产生.既往研究认为其主要功能是通过作用于下丘脑来降低食欲并增加能量消耗,进而调节体重,故称之为瘦素.目前发现Leptin是连接营养和其他牛理功能的代谢信号,不仅在能量代谢中发挥重要作用,还参与了机体免疫调节、血管生成、炎症反应、青春期启动及生殖调节等一系列重要生理活动:而Leptin受体或结合蛋白对Leptin生物学功能的发挥有重要调节作用.尽管人们逐渐认识到Leptin参与生殖调控,但目前研究成果主要集中在女性生殖系统调节方面,Leptin对男性生殖系统的调节机制仍存在诸多问题有待探索.本文就Leptin及其受体或结合蛋白对男性生殖功能的影响作一综述.     

瘦素与早泄关系研究进展

瘦素(Leptin)是一种由肥胖基因(Obesity Gene,OB Gene)编码并主要由脂肪细胞分泌的蛋白质激素,它在食物摄取、能量平衡及体重控制中有重要作用。Leptin通过与受体结合影响下丘脑-垂体-内分泌轴而发挥生理作用,其对5-羟色胺(5- HT)、多巴胺等神经递质均有一定的影响。而5- HI与早泄这种男科常见疾病存在明确的关系,通过5-HT探讨Leptin与早泄的关联性近年来受到关注。本     

血清细胞因子在老年骨质疏松患者中的变化及临床意义

[目的]探讨老年骨质疏松患者瘦素(leptin)、肿瘤坏死因子α(TNF-α)、白介素-2(IL-2)、胰岛素样生长因子1(IGF-1)水平的变化及其临床意义。[方法]选择2010~2014年驻地干休所老年患者80例,根据骨质疏松诊断标准分为骨质疏松组(osteoporosis group,35例)和骨量减少组(osteopenia group,45例),并选择同期老年体检患者30例为对照组。检测外周血血清Leptin、TNF-α、IL-2、IGF-1水平,并测定骨密度。[结果]骨质疏松组及骨量减少组血清IL-2和IGF-1水平均明显低于对照组(P<0.05),血清Leptin和TNF-α水平明显高于对照组(P<0.05);骨质疏松组与骨量减少组骨密度均明显低于对照组(P<0.05),同时骨质疏松组骨密度也明显低于骨量减少组(P<0.05);血清中IL-2和IGF-1水平与骨密度值均呈正相关(r=0.35,0.39,P<0.05),而Leptin、TNF-α与骨密度值呈负相关(r=-0.35,P<0.05)。[结论]Leptin、TNF-α、IL-2及IGF-1对辅助诊断和治疗老年骨质疏松症有一定的临床意义。     

慢性胆囊炎患者血清瘦素及可溶性瘦素受体与血脂水平的变化及关系

目的:探讨慢性胆囊炎患者血清瘦素(Lep)、可溶性瘦素受体(s LR)与血脂水平的变化及其相互关系。方法:选择103例慢性胆囊炎患者,以91例健康体检者为对照,测定所有受试者空腹血清Lep、s LR、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL),分析慢性胆囊炎患者血清Lep、s LR水平与血脂水平的关系。结果:与对照组比较,慢性胆囊炎组患者血清TC、LDL和Lep水平均明显升高,而s LR水平明显降低(均P0.05)。单因素分析显示,Lep水平与TC、TG和HDL水平呈明显正相关(均P0.05),而s LR水平与各血脂指标无明显相关性(均P0.05);多元回归分析显示,Lep水平与TC水平呈明显正相关(P0.05)。结论:慢性胆囊炎患者血清Lep明显升高、s LR水平降低以及血脂代谢紊乱,其中,Lep升高所致胆固醇代谢障碍可能是主要原因。     

Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats

Leptin exerts important effects on the regulation of food intake and energy expenditure by acting in the brain. Leptin is secreted by adipocytes into the bloodstream and must gain access to specific regions in the brain involved in regulating energy balance. Its action is mediated by interaction with a receptor that is mainly expressed in the hypothalamus but is also present in other cerebral areas. To reach these target areas, leptin most likely needs to cross the blood-brain barrier (BBB). In this study, we compared the permeability of leptin at the BBB in homozygous lean (FA/FA), high-fat diet-induced (HFD) obese rats (FA/FA rats on a highfat diet), and genetically obese fa/fa Zucker rats by quantifying the permeability coefficient surface area (PS) product after correction for the residual plasma volume (Vp) occupied by leptin in the vessel bed of different brain regions. The intravenous bolus injection technique was used in the cannulated brachial vein and artery using leptin radioiodinated with 2 isotopes of iodine (125I and 131I) to separately determine the PS and Vp values. The PS for leptin at the BBB in lean FA/FA rats ranged from 11.0 +/- 1.6 at the cortex to 14.8 +/- 1.4 x 10(-6) ml x g(-1) x ml(-1) at the posterior hypothalamus. The PS for leptin in HFD obese FA/FA and obese fa/fa rats ranged from 3.0- to 4.0-fold lower than in lean FA/FA rats. The Vp values were not significantly different among the 3 groups studied. SDS-PAGE analysis of the radioiodinated leptin after 60 min of uptake revealed intact protein in the 8 different brain regions. Plasma leptin levels were significantly higher in both obese rat groups compared with those in lean FA/FA rats. Leptin levels in cerebrospinal fluid were not significantly different among the 3 groups of rats. These findings strongly suggest that the leptin receptor (OB-R) in the BBB can be easily saturated. Saturation of the BBB OB-R in obese individuals would explain the defect in leptin transport into the brain described in this study.     

穴位埋线联合药杖华佗夹脊穴治疗单纯性肥胖症疗效观察

目的:优选提高单纯性肥胖症疗效方案。方法:将100例患者随机分为穴位埋线联合药杖华佗夹脊穴组(治疗组)及毫针法单独体针操作组(对照组),每组各50例,并进行临床疗效对比观察。结果:两组分别于45天后比较疗效,治疗组总有效率(96.18%),与对照组(79.86%)相比具有显著性差异(P0.01)。结论:穴位埋线联合药杖华佗夹脊穴治疗单纯性肥胖症总有效率优于单独体针操作,疗效稳定,不易反弹,且较针刺疗法方便,疗效持久。     

穴位埋线法治疗单纯性肥胖症

目的:探讨穴位埋线治疗单纯性肥胖症的-临床疗效.方法:将126例单纯性肥胖症患者随机分为治疗组(埋线法)56例和对照组(口服西药西布曲明)70例,对治疗前后体重、腰围、臀围、F%、BMI指数比较.结果:两组治疗前后五项指数比较,P＜0.05疗效;两组疗效比较,P＞0.05,说明两组疗效无明显差异.对于腰围、臀围指标的改善治疗组优于对照组.结论:穴位埋线法治疗简便易行,疗效显著,其塑形效果好,值得临床推广.     

Central infusion of histamine reduces fat accumulation and upregulates UCP family in leptin-resistant obese mice

Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activation of histamine signaling in the hypothalamus may have substantial anti-obesity and antidiabetic actions, particularly in leptin-resistant states. To address this issue, effects of central, chronic treatment with histamine on food intake, adiposity, and energy expenditure were examined using leptin-resistant obese and diabetic mice. Infusion of histamine (0.05 pmol x g body wt(-1) x day(-1)) into the lateral cerebroventricle (i.c.v.) for 7 successive days reduced food intake and body weight significantly in both diet-induced obesity (DIO) and db/db mice. Histamine treatment reduced body fat weight, ob gene expression, and serum leptin concentration more in the model mice than in pair-fed controls. The suppressive effect on fat deposition was significant in visceral fat but not in subcutaneous fat. Serum concentrations of glucose and/or insulin were reduced, and tests for glucose and insulin tolerance showed improvement of insulin sensitivity in those mice treated with histamine compared with pair-fed controls. On the other hand, gene expression of uncoupling protein (UCP)-1 in brown adipose tissue and UCP-3 expression in white adipose tissue were upregulated more in mice with i.c.v. histamine infusion than in the pair-fed controls. These upregulating effects of histamine were attenuated by targeted disruption of the H1-receptor in DIO and db/db mice. Sustained i.c.v. treatment with histamine thus makes it possible to partially restore the distorted energy intake and expenditure in leptin-resistant mice. Together, i.c.v. treatment with histamine contributes to improvement of energy balance even in leptin-resistant DIO and db/db mice.     

复方黄芪首乌对肥胖大鼠肾组织ET-1/NOS的表达的干预作用

目的：探讨肥胖大鼠肾组织内皮素（ET-1）和一氧化氮（NO）平衡及中药复方黄芪首乌汤对其干预作用。方法：采用高糖高脂饲料喂养建立实验性肥胖大鼠模型,以复方黄芪首乌汤灌胃治疗,8周末采血检测血脂、血糖和肾功能,并取肾皮质匀浆检测ET-1和NOS含量,逆转录-聚合酶链反应检测肾组织ET-1和NOSmRNA表达。结果：复方黄芪首乌汤组大鼠体重显著下降,与苯那普利对照组结果相似（P〈0.05）;复方黄芪首乌汤能够明显降低肥胖大鼠血清LDL（P〉0.05）,但对实验大鼠的TC、TG和HDL-C作用不显著（P〉0.05）;复方黄芪首乌汤对实验大鼠血糖和Ins作用不明显（P〉0.05）;复方黄芪首乌汤能够下调实验鼠血肌酐和尿素氮水平（P〈0.05）;与正常组比较,肥胖大鼠肾组织NOS活力和基因表达水平显著下降,而ET-1及ET-1mRNA表达水平显著上升,经中药干预治疗后NOS及NOSmRNA表达上调,ET-1及ET-1mRNA表达下调。结论：复方黄芪首乌汤对大鼠肥胖具有一定的防治作用,可以减轻大鼠体重,调节血脂紊乱,保护肾脏功能,同时参与维持肾组织NO/ET-1动态平衡有关。     

Leptin and reproductive dysfunction in obese men

Infertility is somewhat more prevalent in men who are obese. They are also reported to have low sperm concentration, higher fraction of spermatozoa that look morphologically abnormal, higher DNA fragmentation index and evidence of oxidative stress. The precise cause for this remains uncertain. Leptin levels in serum and percentage body fat correlate positively, and obese men therefore usually have elevated serum leptin levels. Although leptin is important for normal reproductive function, but when present in excess, leptin could seriously affect reproductive function in men. Reports on the findings of sperm parameters in obese men, particularly those who are subfertile or infertile, seem to be similar to those reported from studies on normal-weight rats treated with leptin. Collectively, the observations reported in human and experimental animal studies point to leptin as a possible link between infertility and obesity. Herein, we review some findings on sperm function in obese subfertile or infertile men and those from animal studies following leptin treatment, and discuss the possible link between leptin and reproductive dysfunction in obese men. The large amounts of leptin secreted by the adipose tissue and its higher circulating levels could indeed be responsible for the higher prevalence of infertility in obese men.     

Role of selective leptin resistance in diet-induced obesity hypertension

Leptin is an adipocyte-derived hormone that plays a key role in the regulation of body weight through its actions on appetite and metabolism. Leptin also increases sympathetic nerve activity (SNA) and blood pressure. We tested the hypothesis that diet-induced obesity is associated with resistance to the metabolic actions of leptin but preservation of its renal SNA and arterial pressure effects, leading to hypertension. Mice were fed a high-fat diet for 10 weeks to induce moderate obesity. The decrease in food intake and body weight induced by intraperitoneal or intracerebroventricular leptin was significantly attenuated in the obese mice. Regional SNA responses to leptin were differentially altered in diet-induced obese mice. Renal SNA response to leptin was preserved, whereas lumbar and brown adipose tissue SNA responses were attenuated in obese mice. Radiotelemetric arterial pressure was approximately 10 mmHg higher in obese mice. Furthermore, the increase in arterial pressure in response to long-term (12 days) leptin treatment was preserved in obese mice. Thus, mice with diet-induced obesity exhibit circulating hyperleptinemia and resistance to the metabolic actions of leptin. However, there is preservation of the renal sympathetic and arterial pressure responses to leptin, which represent a potential mechanism for the adverse cardiovascular consequences of obesity.