瘦素受体及神经肽Y mRNA在肥胖大鼠下丘脑弓状核的表达

以高脂饮食制备肥胖大鼠模型和用寡核苷酸探针在下丘脑弓状核进行原位杂交检测，结果显示肥胖大鼠下丘脑弓状核瘦素受体mRNA和神经肽Y mRNA表达明显增加，提示可能为瘦素受体抵抗所致。     

丝胶对2型糖尿病大鼠下丘脑神经肽Y和瘦素表达的影响

目的探讨彩色蚕茧提取物———丝胶对2型糖尿病大鼠下丘脑神经肽Y(NPY)和瘦素(Leptin)表达的影响。方法 48只雄性SD大鼠随机分为4组(每组12只):正常组、模型组、丝胶组和二甲双胍组。模型组、丝胶组和二甲双胍组均建立链脲佐菌素(STZ)致糖尿病动物模型,以血糖≥16.7 mmol/L为成模标准;丝胶组和二甲双胍组分别于成模后给予丝胶(2.4 g·kg-1·d-1)和二甲双胍(55.33 mg·kg-1·d-1)灌胃,时间均为35 d。采用酶法检测血糖、RT-PCR法检测下丘脑NPY和Leptin mRNA的表达。结果与正常组大鼠相比,模型组大鼠血糖、NPY和Leptin mRNA表达明显升高(P<0.01);丝胶组大鼠血糖、NPY和Leptin mRNA表达明显低于模型组大鼠(P<0.05),且以上指标和二甲双胍组比较无明显差别(P>0.05)。结论丝胶可下调下丘脑NPY和Leptin mRNA的高表达,从而减轻糖尿病时的中枢损伤,进而改善糖尿病的症状,起到一定的治疗作用。     

Ghrelin与肥胖的研究进展

Ghrelin是迄今发现的体内唯一的生长激素促分泌素受体的内源性配体,它在体内通过中枢食欲调节网络,尤其是神经肽Y,促进摄食;并与多种致肥胖因子如瘦素、胰岛素等有相互作用,在肥胖的病理过程中发挥重要作用。其拮抗剂能阻断Ghrelin的促进摄食的作用,有可能成为治疗肥胖的新一代药物。     

老年人单纯收缩期高血压血清瘦素、抵抗素及血浆同型半胱氨酸、神经肽的水平

目的探讨老年单纯收缩期高血压(ISH)患者血清瘦素(Lep)、抵抗素(Res)与血浆同型半胱氨酸(Hcy)、神经肽Y(NPY)的水平,及与其他类型老年高血压患者、健康老年人之间的差异. 方法对ISH组28例、全期型高血压(SDH)组26例、单纯舒张期高血压(IDH)组25例及老年健康对照组21例,采用酶免疫法检测血清Lep、Res,放射免疫法测定血浆Hcy、NPY,同时检测受试者体质指数(BMI)和体内脂肪(BF)百分比. 结果 ISH组、SDH组、IDH组血清Lep[(13.18±1.66)μg/L、(11.91±2.16)μg/L、(10.88±2.31)μg/L]、Res[(31.2±10.3)μg/L、(26.3±8.91)μg/L、(24.2±5.66)μg/L]水平均高于对照组[(7.71±1.28)μg/L和(19.8±7.21)μg/L,P<0.05或P<0.01],ISH组显著高于SDH、IDH组(P<0.05,P<0.01);3个不同类型高血压组患者的血浆Hcy、NPY较对照组增高(P<0.01,P <0.05),而老年ISH组又较SDH、IDH组增高(P<0.01);老年ISH组平均年龄较其他各组明显增高(P <0.01),老年SDH组较IDH组、对照组也增高(P<0.05, P<0.01);老年ISH组BMI也较其他各组明显增高(P<0.05,P<0.01),而且SDH组较老年健康组显著增高(P<0.05).ISH患者 BF百分比与IDH组、老年健康组差异均有显著性(P<0.05).收缩压与Lep、NPY呈正相关(γ=0.256,P <0.05;γ=0.374,P<0.01). 结论 Lep、Res、Hcy及NPY与老年人高血压发病,尤其是老年ISH的发病有关,控制患者血清Lep、Res、血浆Hcy及NPY浓度对预防老年高血压,尤其是ISH的发生或发展可能有积极作用.     

脑出血大鼠血浆神经肽Y及血清肌酸磷酸激酶MB型的变化

目的　观察实验性脑出血条件下血浆神经肽Y(NPY)及肌酸磷酸激酶MB型 (CK MB)含量的动态变化 ,以探讨脑心综合征的发生机制。方法　采用胶原酶和肝素联合注入尾状核方法建立大鼠脑出血模型 ,测定出血前、出血后 30min、6、12、2 4、4 8及 72h血浆NPY活性及血清CK MB变化。采用放射免疫法测定血浆NPY的变化 ,采用酶反应速率法测定血清CK MB的变化。结果　大鼠脑内血肿开始形成的 6h血浆NPY活性、血清CK MB均较术前水平及对照组显著升高 (P <0 .0 5 ) ,并以脑出血 2 4h血肿高峰期时最为显著 (P <0 .0 1) ,随后逐渐下降 ,72h仍高于术前水平及对照组 (P <0 .0 5 )。结论　脑出血时常伴有血清CK MB改变 ,外周NPY含量升高可能参与脑心综合征的发生发展。     

Ghrelin和下丘脑神经肽Y在2型糖尿病大鼠发病过程中的变化

目的观察在2型糖尿病(T2DM)大鼠模型形成过程中ghrelin和下丘脑神经肽Y(NPY)的变化,探讨ghrelin及NPY在T2DM大鼠发病过程中的作用。方法选择SD大鼠60只,分为对照组15只、高脂饮食诱导肥胖(DIO)4周组(DIO 4周组)15只(高脂饮食喂养4周)、DIO 8周组15只(高脂饮食喂养8周)和T2DM组15只。以DIO结合小剂量链脲佐菌素(15mg/kg)法建立T2DM大鼠模型。应用酶联免疫吸附法检测大鼠空腹血浆及胃组织匀浆ghrelin水平;RT-PCR法检测下丘脑NPY mRNA的表达变化。结果与对照组比较,DIO4周组、DIO8周组和T2DM组大鼠血浆和胃组织ghrelin水平明显降低(P<0.01),NPY mRNA表达明显升高[(1.18±0.14)、(1.54±0.09)和(1.82±0.12)vs(0.88±0.17),P<0.01]。NPY mRNA与ghrelin水平呈负相关(r=-0.989,P<0.01)。结论 ghrelin可能通过刺激下丘脑NPY的合成和分泌,共同参与T2DM的形成。     

下丘脑和神经肽在肥胖形成机制中的研究进展

下丘脑在维持能量代谢活动中发挥关键作用,下丘脑核团之间通过神经肽形成的调控网络是能量平衡的基础.因此,下丘脑能量平衡调节异常可能是肥胖形成的中枢机制.本文对近年肥胖形成的中枢方面的理论以及神经肽在下丘脑内的调节作用进行综述.     

原发性高血压患者血浆瘦素与神经肽Y浓度测定的意义

目的　研究原发性高血压患者神经肽Y与瘦素的相互关系。方法　采用放免分析法测定 2 6例健康对照者和原发性高血压 1级 4 2例、2级 4 6例及 3级 2 8例患者的空腹血浆瘦素 (LE)及神经肽Y (NPY)浓度。结果　血浆LE及NPY浓度均随血压的升高而升高 (F分别为 4 0 2和31 4 ,P均 <0 0 0 1) ,在正常对照组和高血压各组间均有显著性差异。相关分析表明 ,NPY和LE均与血压呈显著正相关 ,控制LE的影响后NPY仍与血压呈正相关 (P均 <0 0 5 ) ,而控制NPY的影响后LE与血压的相关性不再有显著性 (P >0 0 5 )。NPY浓度与LE浓度呈显著正相关 (R =0 5 5 9,P<0 0 0 0 1) ,同时控制性别、血压、血脂、BMI和HOMA IR的影响后两者仍呈显著正相关 (R =0 337,P <0 0 0 0 1)。结论　高血压患者存在瘦素抵抗 ,瘦素抵抗可能是高血压患者NPY升高的主要原因 ,而NPY的升高一方面可使血压升高 ,另一方面可能进一步加重瘦素抵抗。     

神经肽Y Y5受体基因反义寡核苷酸脑室给药对大鼠血清瘦素、胰岛素及TNF-α水平的影响

目的 观察神经肽Y Y5(NPY Y5)受体基因反义寡核苷酸脑室给药对伴糖尿病缺血再灌注(I/R)大鼠血清瘦素、胰岛素与TNF-α水平的影响.方法 链脲佐菌素空腹腹腔注射制备糖尿病大鼠模型,线栓法闭塞大脑中动脉制作脑I/R大鼠模型;治疗组经导管向脑室注入50 μg(5 μg/μl)NPY Y5受体基因反义寡核苷酸,每天3次给药,连续用药3 d;采用ELISA双抗体夹心法测定血清TNF-α与瘦素含量,放射免疫法测定胰岛素含量. 结果 I/R损伤后,大鼠血清瘦素、胰岛素、TNF-α水平较对照组显著升高(P＜0.05,P＜0.01);NPY Y5受体基因反义脱氧核苷酸侧脑室注射干预后,其血清瘦素、胰岛素水平明显下降(P＜0.05),TNF-α水平显著降低(P＜0.01).结论 神经肽Y Y5受体基因反义寡核苷酸侧脑室给药可降低伴糖尿病I/R大鼠的血清瘦素、TNF-α与胰岛素水平,改善外周瘦素抵抗与胰岛素抵抗(IR),促进脑梗死恢复.     

Influence of short- and long-term treadmill exercises on levels of ghrelin, obestatin and NPY in plasma and brain extraction of obese rats

This study aims to clarify the effects of exercise on levels of appetite regulatory hormones in plasma and hypothalamus of obese rats. Diet-induced obese rats undergo short- (40 min) and long-term (40 min, 5 days/week for 8 weeks) exercises. The rats ran at a speed of 20 m/min on a 5° slope treadmill. Rats undergoing short-term exercise were divided into C, E0, E1, E3, E12, and E24. Rats undergoing long-term exercise (LE) were compared to long-term control (LC). Concentrations of ghrelin, obestatin, and neuropeptide Y (NPY) were measured using radio immuno-assay. Expression of ghrelin receptor (GHSR-1a), putative obestatin receptor (GPR-39), and NPY in the hypothalamus was measured by quantitative RT-PCR. After short-term exercise, the plasma concentrations of ghrelin and obestatin were not changed, but NPY decreased. Ghrelin and obestatin in the hypothalamus decreased, and recovered 12 until 24 h. NPY increased and recovered after 24 h. Expression of GHSR-1a and NPY was not changed and GPR-39 was not observed. In LE, these changes are different in plasma and hypothalamus. It would be concluded appetite and body weight of obese rats are decreased by exercise through reduced level of ghrelin in the hypothalamus. Obestatin seems to have no effect in exercise-induced change in appetite.     

The change of plasma ghrelin and leptin levels by the development of type 2 diabetes mellitus in patients with alcohol dependence

Background: There have been lots of studies about the relationship between chronic use of alcohol and the development of type 2 diabetes mellitus (T2DM). Chronic use of alcohol can be affected by the altered level of ghrelin and leptin which regulate food‐seeking behavior having similar mechanism of controlling alcohol‐craving behavior. Those peptides are known to be correlated with T2DM. Ghrelin and leptin also have been regarded as possible regulators of glucose metabolism and insulin function. Hence, there is the possibility that ghrelin and leptin can be related with deteriorated pathophysiology of T2DM in alcoholic patients. Methods: Patients with alcohol dependence diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) underwent an 75 g oral glucose‐tolerance test (OGTT), to classify them to normal glucose tolerance (NGT, n = 52), pre‐diabetes including impaired glucose tolerance (IGT), impaired fasting glucose level (IFG) and combination of IGT and IFG (Pre‐DM, n = 26) and T2DM (n = 24) groups. Fasting plasma ghrelin and leptin levels were compared among groups. Results: There was no difference of ghrelin concentration among the groups but the leptin concentration was significantly different between NGT and T2DM group (p < 0.05). Increased leptin levels were significantly correlated with body mass index (BMI), insulin level, and insulin resistance. Conclusions: Chronic alcohol drinking might produce leptin resistance which makes leptin significantly correlated with fasting insulin concentration and insulin resistance. Therefore, we suppose that increased level of leptin by chronic alcohol use could be one of the main mechanisms that develop insulin resistance in alcoholic patients.     

Ghrelin改善果糖诱导大鼠胰岛素抵抗的机制研究

32只雄性SD大鼠分为正常对照组(n=16)和果糖组(n=16),分别予以正常饮水和10％果糖4周,2组再分别以生理盐水和50 nmol/kg胃促生长素(Ghrelin)干预6周(每组n=8),测定空腹血糖、血脂和胰岛素等生化指标,RT-PCR检测大鼠骨骼肌胰岛素受体(Ins-R) mRNA表达水平,Western印迹法检测胰岛素受体底物1(IRS-1)的磷酸化水平.结果显示,高果糖组大鼠血浆胰岛素浓度和稳态模型评估的胰岛素抵抗指数(HOMA-IR)均较正常对照组明显升高[(13.1±3.6对9.0±1.5)μU/ml,P＜O.05;2.78±0.14对1.81 ±0.13,P＜0.01)],而高果糖喂养的大鼠经Ghrelin干预后胰岛素水平[(9.6±2.5) μU/ml,P＜0.05]和HOMA-IR(1.96±0.12,P＜0.01)明显降低,骨骼肌Ins-R mRNA表达和IRS-1磷酸化水平明显升高(P＜0.01),提示Ghrelin可能通过恢复骨骼肌Ins-R和受体后功能,改善胰岛素抵抗.     

Effect of chronic hypoxia on leptin, insulin, adiponectin, and ghrelin

The endocrine system plays an important role in the adaptation to hypoxia. The aim of this study was to assess the effect of chronic hypoxia on insulin, adiponectin, leptin, and ghrelin levels in a neonatal animal model. Sprague-Dawley rats were placed in a normobaric hypoxic environment at birth. Controls remained in room air. Rats were killed at 2 and 8 weeks of life. Insulin, adiponectin, leptin, and ghrelin were measured. At 2 weeks of life, there was no significant difference in insulin, adiponectin, and leptin levels between the hypoxic and control rats. The only statistically significant difference was found in ghrelin levels, which were lower in the hypoxic group (3.19 ± 3.35 vs 24.52 ± 5.09 pg/mL; P < .05). At 8 weeks of life, insulin was significantly higher in the hypoxic group (0.72 ± 0.14 vs 0.44 ± 0.26 ng/mL; P < .05) and adiponectin was significantly lower (1257.5 ± 789.5 vs 7817.3 ± 8453.7 ng/mL; P < .05). Leptin and ghrelin did not show significant difference in this age group, but leptin level per body weight was higher in the hypoxic group. Finally, we conclude that 2 weeks of continuous neonatal hypoxic exposure leads to a decrease in plasma ghrelin only with no significant change in insulin, adiponectin, and leptin and that 8 weeks of hypoxia leads to a decrease in adiponectin with an increase in insulin despite a significant decrease in weight.     

Circulating leptin and insulin in obese patients with and without type 2 diabetes mellitus: relation to ghrelin and oxidative stress

Aim

This case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients.

Methods

Thirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits.

Results

Serum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes.

Conclusions

Our results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients.     

Ghrelin与能量平衡及糖代谢的关系

Ghrelin是生长激素促分泌物受体的第一个内源性配体,具有促进生长激素分泌、促进摄食、减少脂肪利用等作用,并与胰岛素、瘦素等相互作用,影响能量平衡及糖代谢,因而与肥胖、胰岛素抵抗及2型糖尿病密切相关。进一步研究ghrelin的作用对研究肥胖、胰岛素抵抗、2型糖尿病的发生、发展过程具有指导意义。     

Hormonal protection in acute pancreatitis by ghrelin,leptin and melatonin

Acute pancreatitis is a nonbacterial disease of the pancreas.The severe form of this ailment is characterized by high mortality.Whether acute pancreatitis develops as the severe type or resolves depends on the intensity of the inflammatory process which is counteracted by the recruitment of innate defense mechanisms.It has been shown that the hormones ghrelin,leptin and melatonin are able to modulate the immune function of the organism and to protect the pancreas against inflammatory damage.Experimental studies have demonstrated that the application of these substances prior to the induction of acute pancreatitis significantly attenuated the intensity of the inflammation and reduced pancreatic tissue damage.The pancreatic protective mechanisms of the above hormones have been related to the mobilization of non-specific immune defense,to the inhibition of nuclear factor kappa B and modulation of cytokine production,to the stimulation of heat shock proteins and changes of apoptotic processes in the acinar cells,as well as to the activation of antioxidant system of the pancreatic tissue.The protective effect ofghrelin seems to be indirect and perhaps dependent on the release of growth hormone and insulin-like growth factor 1.Leptin and ghrelin,but not melatonin,employ sensory nerves in their beneficial action on acute pancreatitis.It is very likely that ghrelin,leptin and melatonin could be implicated in the natural protection of the pancreatic gland against inflammatory damage because the blood levels of these substances increase in the initial phase of pancreatic inflammation.The above hormones could be a part of the innate resistance system which might remove noxious factors and could suppress or attenuate the inflammatory process in the pancreas.     

Role of feeding-related pathways in alcohol dependence: A focus on sweet preference, NPY, and ghrelin

Converging research evidence suggests that alcohol and food-seeking behaviors share common neural pathways. There is preclinical and clinical evidence linking the consumption of sweets to alcohol intake in both animals and humans. In addition, a growing body of animal and human literature suggests the involvement of "feeding-related" peptides in alcohol-seeking behavior. In particular, both central and peripheral appetitive peptides have shown a possible role in alcohol dependence. The present mini-review will summarize the literature on the link between sweet preference and alcohol dependence, and on the role of feeding-related peptides in alcohol dependence. Specifically, in an attempt to narrow the field, the present mini-review will focus on 2 specific pathways, the central neuropeptide Y and the peripheral gut peptide ghrelin. Although more research is needed, data available suggest that studying feeding-related pathways in alcohol dependence may have theoretic, biologic, diagnostic, and therapeutic implications.     

代谢综合征幼鼠脑组织ghrelin含量与代谢紊乱关系的研究

目的 通过建立幼年代谢综合征大鼠模型,探讨其脑组织ghrelin的含量及其与肥胖、代谢紊乱的关系.方法 将40只3周龄断乳幼鼠(雌、雄各20只)按随机数字表法随机分为3组:即普通饮食组(NC组)、高脂饮食组(FC组)、高脂及高盐饮食组(FSC组),分别予普通饮食、高脂饮食、高脂及高盐饮食.4周后,测量血压、体重、腹围、内脏脂肪重量等指标,取血测血脂指标,经胃管注入50％葡萄糖(2 g/kg)行口服葡萄糖耐量试验(OGTT)及胰岛素释放试验,测定各时间点血糖及胰岛素浓度.处死后取脑组织,ELISA法测定3组幼鼠脑组织内ghrelin的含量.结果 (1) FSC组的收缩压、舒张压、腹围、内脏脂肪重量均高于NC组(q=12.016,7.183,1.449,1.095,P＜0.05),FSC组内脏脂肪重量高于FC组(q=1.657,P ＜0.05).(2) FSC组的总胆固醇、甘油三酯和低密度脂蛋白-胆固醇水平均显著高于NC组,而高密度脂蛋白-胆固醇水平低于NC组(q=6.915,2.231,2.472,-2.456,P＜0.05),FSC组的甘油三酯水平高于FC组(q=3.055,P＜0.05),高密度脂蛋白-胆固醇水平低于FC组(q=-2.302,P ＜0.05).(3)FSC组OGTT及胰岛素释放试验中0,60,120,180 min的血糖及胰岛素水平均高于NC组(q=2.586,3.786,1.171,4.028,11.136,7.558,13.003,6.189,P＜0.05).同时,FSC组稳态模型评估-胰岛素抵抗指数亦高于NC组(q=8.352,P＜0.05),FSC组0,60,120,180 min胰岛素水平均显著高于FC组(q=8.956,4.433,11.220,5.641,P＜0.05).(4)FSC组脑组织内ghrelin的含量低于NC组(q=-0.506,P＜0.05),而FC组脑组织内ghrelin的含量高于NC组(q=1.686,P＜0.05).结论 高盐、高脂饮食可建立幼年代谢综合征大鼠模型.其脑组织ghrelin可能通过增强食欲、促进摄食等行为,在中枢水平对代谢综合征及肥胖的发生、发展过程起重要作用.