解耦联蛋白在心肌中的表达与心力衰竭

位于心肌线粒体内膜上的解耦联蛋白 (UCPs) ,作为质子通道驱散氧化呼吸时形成的H 梯度 ,使产能转化为产热 ,从而增加呼吸 ,阻止ATP形成 ,并抑制活性氧族的产生 ,最终阻止了心肌细胞的程序性死亡。脂肪酸、寒冷、甲状腺激素、肾上腺素等能调控UCPs的浓度和活性。UCPs在心力衰竭中的作用仍然不清楚 ,有待进一步研究     

外源性CoQ10对大鼠心肌损伤中解偶联蛋白2基因表达的影响

目的:观察解偶联蛋白2(UCP2)mRNA在大鼠损伤心肌中的表达及应用外源性辅酶Q10(CoQ10)后,UCP2 mRNA表达的变化及其对心肌的保护作用。方法:采用大剂量异丙肾上腺素(ISO)多点皮下注射造成大鼠心肌损伤模型,36只健康SD大鼠随机平均分为3组:对照组I、SO组、ISO+CoQ10组。Ⅱ导联心电图检测心肌缺血损伤程度,光镜观察心肌病理损伤程度,生化方法检测心肌内超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,RT-PCR方法检测心肌细胞内UCP2 mRNA的表达水平。结果:ISO+CoQ10组与ISO组比较,心肌病理损伤程度明显减轻,J点下降减少,MDA含量显著减少,SOD活性增强,UCP2 mRNA的表达明显增加(P<0.01)。结论:UCP2 mRNA的高表达可起到保护心肌的作用,而CoQ10能通过介导其高表达发挥治疗作用。     

解偶联蛋白2对非酒精性脂肪肝病肝细胞氧化应激的影响

非酒精性脂肪肝是临床常见疾病,其发病机理尚未完全明确,氧化应激被认为是其机理之一,文章就解偶联蛋白2对非酒精性脂肪肝肝细胞氧化应激的影响作一综述。     

Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians

Aims/hypothesis Uncoupling protein-2 (UCP2) is thought to play a role in insulin secretion and the development of obesity. In this study, we investigated the effects of genetic variation in UCP2 on type 2 diabetes and obesity, as well as on metabolic phenotypes related to these diseases, in Pima Indians.Methods The coding and untranslated regions of UCP2, and approximately 1 kb of the 5 upstream region, were sequenced in DNA samples taken from 83 extremely obese Pima Indians who were not first-degree relatives.Results Five variants were identified: (1) a –866G/A in the 5 upstream region; (2) a G/A in exon 2; (3) a C/T resulting in an Ala55Val substitution in exon 4; and (4, 5) two insertion/deletions (ins/del; 45-bp and 3-bp) in the 3 untranslated region. Among the 83 subjects whose DNA was sequenced, the –866G/A was in complete genotypic concordance with the Ala55Val and the 3-bp ins/del polymorphism. The G/A polymorphism in exon 2 was extremely rare. To capture the common variation in this gene for association analyses, the –866G/A variant (as a representative of Ala55Val and the 3-bp ins/del polymorphism) and the 45-bp ins/del were also genotyped for 864 full-blooded Pima Indians. Neither of these variants was associated with type 2 diabetes or body mass index. However, in a subgroup of 185 subjects who had undergone detailed metabolic measurements, these variants were associated with 24-h energy expenditure as measured in a human metabolic chamber (p=0.007 for the 45-bp ins/del and p=0.03 for the –866G/A after adjusting for age, sex, family membership, fat-free mass and fat mass).Conclusions/interpretation Our data indicate that variation in UCP2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in Pima Indians.     

南京地区2型糖尿病患者解偶联蛋白2基因-866G/A多态性与胰岛功能相关性研究

目的研究南京地区汉族人群2型糖尿病解偶联蛋白2(UCP2)基因启动子区-866G/A多态性与胰岛功能的相关性。方法对2006年1～9月在南京大学医学院附属鼓楼医院收集的229例2型糖尿病患者以及196例正常对照者UCP2基因-866G/A位点进行基因分型,并行口服葡萄糖耐量加同步胰岛素释放试验检测胰岛B细胞分泌功能及胰岛素敏感性。结果UCP2基因-866G/A位点的基因型频率和等位基因频率在2型糖尿病与对照组中分布差异有显著性意义(分别为χ2=6.555,P=0.038;χ2=6.363,P=0.012),2型糖尿病组中A/A基因型和A等位基因频率显著高于正常对照(分别为OR=1.99,OR=1.42,均P<0.05);2型糖尿病组中G/A、A/A基因型携带者的早期相胰岛素分泌均低于G/G基因型携带者[1.55(0.77,2.40)对2.46(1.44,4.70),1.23(0.43,2.71)对2.46(1.44,4.70),均P<0.01]。结论UCP2基因启动子区-866G/A多态性与南京地区汉族人群2型糖尿病及胰岛功能存在相关性,UCP2基因可能是2型糖尿病的易患基因之一。     

Prolongation of tension on reoxygenation following myocardial hypoxia: a possible role for mitochondria in muscle relaxation.

The mechanism for tension prolongation during reoxygenation following myocardial hypoxia was investigated. It was found that prior addition of isoproterenol, reserpine, quinidine, lidocaine and insulin or a change in pH, temperature, stimulation rate, preload or duration of hypoxia did not qualitatively alter the appearance of the phenomenon. On reoxygenating hypoxic preparations in the presence of 5, 10 or 20% oxygen, tension prolongation was clearly present when little increase in isometric tension was evident. Inhibition of glycolysis by iodoacetate did not alter the appearance of the phenomenon during reoxygenation. Three respiratory inhibitors, antimycin A, rotenone and cyanide, at concentrations which did not prevent an increase in isometric tension during recovery from myocardial hypoxia, all completely prevented the appearance of tension prolongation. Two uncouplers of oxidative phosphorylation, 2–4 dinitrophenol and carbonyl cyanide m-chlorophenyl hydrazone at concentrations large enough to lead to mechanical deterioration despite the presence of oxygen, failed to prevent the appearance of tension prolongation upon reoxygenation. It is concluded that myocardial respiratory activity, independent of ability to generate high energy phosphate, appears capable of altering the duration of mechanical events during reoxygenation of hypoxic heart muscle.     

酒精性肝病大鼠肝组织解偶联蛋白2的表达

解偶联蛋白(UCP)是线粒体内膜上可以调节质子跨膜转运的载体蛋白,具有解偶联活性,目前共发现5个亚型[1-2].其中U CP2通过调节质子跨膜转运参与能量消耗和脂质代谢,可能参与酒精性肝病(ALD)发病过程中的氧化应激与脂质过氧化.本研究旨在应用酒精灌胃建立大鼠ALD模型,动态观察UCP2蛋白及mRNA的表达情况,以探讨UCP2在ALD发病过程中的作用及其机制,为有效防治ALD提供新的理论依据.     

瘦素、脂肪酸对大鼠胰岛细胞解偶联蛋白2 mRNA表达的影响

以瘦素、脂肪酸作用于体外培养的大鼠胰岛细胞，以甘油三酯含量，解偶联蛋白2 mRNA表达水平为指标，显示瘦素通过外周途径调节产热，脂肪酸可损害胰岛功能。     

Medium-Chain Triglyceride Activated Brown Adipose Tissue and Induced Reduction of Fat Mass in C57BL/6J Mice Fed High-fat Diet

Objective To investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT). Methods 30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein ofβ3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05). Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.