脑卒中患者急性期血浆抵抗素和瘦素水平及其相关性研究

目的探讨脑卒中患者急性期血浆抵抗素、瘦素水平及与年龄、血压、血糖(Glu)、血脂、胰岛素的关系。方法选择59例脑出血(脑出血组)患者、54例脑梗死(脑梗死组)患者和57例健康老年人(对照组),采用酶联免疫法测定各组患者空腹血浆抵抗素、瘦素水平,同时检测空腹Glu、血脂、胰岛素,测量血压,进行各组比较。结果无论脑出血组还是脑梗死组抵抗素、瘦素水平都明显高于对照组,差异有显著性(P<0.05)。采用相关分析发现,脑出血组抵抗素和收缩压(SBP)、Glu、胰岛素均呈显著正相关(P<0.01),脑梗死组抵抗素和Glu、TG、胰岛素均呈显著正相关(P<0.05)。脑出血组瘦素和SBP、Glu、胰岛素均呈显著正相关(P<0.05或P<0.01),和高密度脂蛋白呈显著负相关(P<0.05),脑梗死组瘦素和SBP、DBP、Glu、胰岛素均呈显著正相关(P<0.05或P<0.01),脑出血组、脑梗死组抵抗素和瘦素浓度都呈显著正相关(P<0.05)。结论脑卒中急性期血浆抵抗素、瘦素水平升高,可能通过联合影响机体能量代谢和平衡,在脑卒中发生过程中发挥重要调控作用。     

二甲双胍刺激肝脏瘦素受体基因表达上调血浆可溶性瘦素受体水平

目的 探讨二甲双胍上调血浆可溶性瘦素受体(soluble leptin receptor,sOB-R)的可能机制.方法 42只6～8周龄健康雄性C57BL/6小鼠,按随机数字表法分为正常饮食(CD)组(n=21)及高脂饮食(HF)组(n=21).喂养5月后,CD组及HF组分别再随机分为3个亚组,每组7只,分别予蒸馏水(不用药对照组),二甲双胍50、200 mg/(kg·d)灌胃,灌胃15 d后取其血浆及肝、肾组织.ELISA法检测小鼠血浆可溶性瘦素受体(soluble leptin receptor,sOB-R)水平,Real-time PCR检测肝、肾脏组织中瘦素受体基因(OB-Rt、OB-Ra、OB-Rb、OB-Rc、OB-Rd)及解聚素样金属蛋白酶10(a disintegrin and metalloproteinase 10,ADAM10)、ADAM17基因的表达,Western blot检测肝、肾脏组织中ADAM10、ADAM17蛋白的表达.结果 与不用药对照组比较,给予不同剂量的二甲双胍后均能升高CD组和HF组小鼠血浆sOB-R,CD组中二甲双胍200 mg/(kg·d)组与其他2组比较,HF组中二甲双胍50、200 mg/(kg·d)组与不用药对照组比较,差异有统计学意义(P ＜0.05,P＜0.01);sOB-R水平升高具有二甲双胍剂量依赖性效应.二甲双胍能上调肝脏瘦素受体基因OB-Rt mRNA的表达,并呈剂量依赖性升高,HF组瘦素受体上升更为明显;瘦素受体亚型OB-Ra、OB-Rc、OB-Rd的上升趋势与OB-Rt趋势一致.肾脏组织中,瘦素受体基因OB-Rt、OB-Ra、OB-Rb、OB-Rc、OB-Rd的表达水平在二甲双胍用药组及不用药对照组相比没有显著变化,CD组与HF组之间也没有显著差异.肝脏和肾脏组织中ADAM10、ADAM17表达量在CD组与HF组、二甲双胍用药组及不用药对照组之间均无显著改变.结论 二甲双胍能显著上调血浆sOB-R水平,该作用主要是通过刺激肝脏瘦素受体基因表达实现的,最主要的来源是肝脏的短型瘦素受体.     

Quantitative trait loci for obesity and insulin resistance (Nob1, Nob2) and their interaction with the leptin receptor allele (LeprA720T/T1044I) in New Zealand obese mice

Abstract Aims/hypothesis. To locate genes responsible for obesity and insulin resistance, a backcross model of New Zealand obese (NZO) mice with the lean Swiss/Jackson Laboratory (SJL) strain was stablished. Results. In female NZO x F1 backcross mice, two major quantitative trait loci for variables of obesity (body weight, body mass index, total body fat) and insulin resistance (hyperinsulinaemia) were identified on chromosomes 5 (Nob1) and 19 (Nob2) close to the markers D5Mit392 and D19Mit91. The aberrant alleles have presumably contributed by the NZO genome. Whereas Nob1 contributed mainly to higher body weight, Nob2 seemed to mainly aggravate insulin resistance independent of obesity. The leptin receptor variant of NZO (Lepr ^A720T/T1044I) failed to alter any of the variables of obesity. It seemed, however, to enhance the effect of Nob1 on body weight and that of Nob2 on serum insulin concentration. When expressed in COS-7 cells, Lepr ^A720T/T1044I produced a normal basal and maximum activation with a minor increase in the EC₅₀ of leptin. Conclusions/interpretation. The data identify two new quantitative trait loci that are responsible for a major part of obesity and hyperinsulinaemia as produced by recessive genes in NZO mice. Lepr ^A720T/T1044I alone cannot produce obesity, but may enhance the effects of other obesity/insulin resistance genes in this mouse model. [Diabetologia (2000) 43: 1565–1572] Received: 20 March 2000 and in final revised form: 11 August 2000     

Effects of high-intensity exercise on leptin and testosterone concentrations in well-trained males

Objective: A number of investigations have examined the effect of exercise on leptin concentrations, because leptin is associated with obesity, satiety, and reproductive function. High-intensity exercise is known to increase testosterone, an inhibitor of leptin. The objective of the study was to determine whether the leptin responses to a progressive, intermittent exercise protocol were related to serum testosterone concentrations. Most previous studies have examined leptin responses to low or moderately high exercise intensities. A second objective was to determine whether leptin responses were different than previous experiments using intermittent moderate and high-intensity exercise. Methods: Well-trained runners completed strenuous intermittent exercise consisting of treadmill running at 60, 75, 90, and 100% VO _2max and a subsequent resting control trial was also conducted. Results: There were significant increases in mean serum levels of leptin and testosterone with both quickly returning to baseline during recovery, but no relationship between the two hormones was found. After examining individual data for both hormones, it was discovered that subjects could be classified as leptin responders or nonresponders, whereas testosterone increased in all subjects. Responders had elevated serum leptin levels at baseline and exhibited increases after high-intensity exercise, whereas nonresponders did not show changes in leptin during exercise. Conclusions: Data suggest testosterone levels do not acutely affect leptin responses to exercise or 1-h of recovery. Moreover, varied leptin responses to intense exercise in comparable well-trained runners was observed and was associated with baseline leptin concentrations.     

Serum leptin levels in gastric cancer patients and the relationship with insulin resistance

Introduction

Serum leptin levels have been examined in various cancers, with conflicting results. However, there is limited information regarding serum leptin levels and insulin resistance in gastric cancer patients. Therefore, we aimed to investigate serum leptin levels, performance status, insulin levels and insulin resistance in patients with gastric cancer. In addition, we examined the relationship between these measurements and leptin levels.

Material and methods

Thirty-nine patients with gastric cancer and 30 control subjects were enrolled in the study. Serum leptin, total protein, albumin, growth hormone, insulin and glucose levels were measured. The homeostasis model assessment (HOMA) was used to assess insulin resistance.

Results

Serum levels of insulin, glucose and growth hormone and insulin resistance were significantly lower in gastric cancer patients than controls (p < 0.05 for all). In the Pearson correlation analysis, insulin resistance was found to be significantly correlated with serum leptin levels in gastric cancer patients (r = 0.320, p = 0.047). We observed a significant negative correlation between performance status and insulin resistance in patients with cachexia (r = –0.512, p = 0.030), while no association was found in non-cachectic patients.

Conclusions

We concluded that serum leptin levels are significantly lower in gastric cancer patients. In addition, gastric cancer patients have decreases in insulin levels, insulin resistance and growth hormone levels. This study found a positive association between serum leptin levels and insulin resistance. Moreover, there is a negative association between serum leptin levels and growth hormone levels. Thus, low insulin and growth hormone levels may suppress the production of leptin in gastric cancer patients.     

COPD患者体内血清瘦素与hs-CRP的相关性

目的 探究血清瘦素（LP）和高敏C反应蛋白（hs-CRP）水平在慢性阻塞性肺疾病（COPD）患者体内浓度的临床变化及两者间的相关性.方法 纳入依据COPD诊治指南中确诊的急性加重期的患者102例为急性加重期组,缓解期的患者132例定为稳定期组,体检健康者158名定为对照组.收集患者相关临床资料,采用比浊法检测血清高敏C反应蛋白水平,酶联免疫吸附法测定血清瘦素水平.应用Pearson相关分析分析瘦素与C反应蛋白及其他因素的相关性.结果 急性加重期组血清瘦素和高敏C反应蛋白水平最高,血清瘦素水平和高敏C反应蛋白水平三组间比较差异有统计学意义（P＜0.05）.经简单相关分析显示,血清瘦素和C反应蛋白间有相关性（r=0.435,P＜0.05）.结论 无论是COPD的缓解期还是急性加重期均存在炎症反应.血清瘦素在COPD的发病机制中可能通过炎症反应参与病变的相关过程.