老年大鼠骨骼肌腺苷酸活化蛋白激酶对胰岛素敏感性的影响

胰岛素抵抗（insulin resistanse IR）是2型糖尿病的主要发病机制和心血管疾病的危险因素。随着年龄的增长,IR和2型糖尿病的发生呈增高趋势,但年龄相关的IR发生的确切机制仍不清楚。有研究表明,腺苷酸活化蛋白激酶（AMPK）通过使其下游酶的磷酸化,在提高脂肪酸氧化方面起了关键作用。我们于2006年10月至2007年2月观察了老年大鼠骨骼肌AMPKα表达和活性，探讨其在脂质堆积和IR中的作用。     

腺苷酸活化蛋白激酶对糖脂代谢的影响

腺苷酸活化蛋白激酶（AMPK）是一种重要的代谢应激蛋白激酶，在运动、缺氧等应激条件下可被高浓度的腺苷酸别构激活，AMPK一旦活化就可以使许多参与葡萄糖摄取和脂肪酸氧化的蛋白磷酸化，促进葡萄糖摄取，增加脂肪酸氧化，增加能量消耗，并且可以调控葡萄糖诱导基因的转录。5-氨基-4-甲酰胺噗唑核糖核苷酸（AICAR）是AMPK的非特异性激动剂，运动的急性效应（增加骨骼肌葡萄糖撮取）和慢性效应（增加葡萄糖转运子4）都可以被AICAR所重复。AMPK可能在2型糖尿病的运动治疗中发挥了重要作用。     

α-硫辛酸对糖尿病大鼠糖外周组织内UCP2 mRNA表达的影响及意义

目的 探讨α-硫辛酸对糖尿病大鼠血脂、血糖、FINS及骨骼肌、脂肪组织内UCP2 mRNA的影响及意义.方法 30只Wistar大鼠随机分为正常对照(NC)组、糖尿病对照(DC)组、α-硫辛酸治疗(LA)组.应用链脲佐菌素(STZ)单次腹腔注射造模.NC组、DC组每只给予生理盐水2 ml/d,LA组60 mg·kg-1·d-1腹腔注射共4 w.测定各组的体重、血糖、糖化血红蛋白(HbA1c)、血脂,并检测脂肪及骨骼肌组织内UCP2 mRNA、丙二醛(MDA)、总抗氧化能力(T-AOC)的水平.结果 DC组甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、HbA1c、胰岛素水平显著高于NC组,而高密度脂蛋白(HDL)水平显著下降,较NC组有显著性差异(P＜0.05);LA组大鼠血浆TG、TC、LDL、HbA1c、胰岛素水平均较DC组显著下降,而HDL显著升高(P＜0.05).DC组脂肪及骨骼肌组织内MDA及UCP2表达水平显著高于NC组,而T-AOC水平显著降低,LA组大鼠组织内MDA水平及UCP2表达均较DC组显著下降,而T-AOC显著升高(P＜0 05).结论 α-硫辛酸干预可明显减少其肝脏、脂肪骨骼肌组织内UCP2表达,改善糖尿病机体的“糖脂毒性”,并进一步改善氧化应激状态,提高机体的抗氧化能力.     

腺苷酸活化蛋白激酶对糖尿病大鼠非酒精性脂肪性肝病的影响

目的 观察腺苷酸活化蛋白激酶（AMPK）在糖尿病大鼠肝脏的表达,探讨其在非酒精性脂肪性肝病（NAFLD）发病中的作用.方法 40只雄性SD大鼠随机分为正常对照（NC）组、饮食诱导肥胖（DIO）组、糖尿病（DM）组.采用Western-blot方法测定肝脏AMPK蛋白表达;HE染色后观察肝脏形态学变化.结果 DIO组血清FIns、HOMA-IR及肝脏TG含量均较NC组升高;DM组FIns、HOMA-IR较NC组及DIO组升高;DIO组肝AMPK蛋白较NC组降低（P＜0.05）;DM组肝AMPK蛋白表达较DIO组降低（P＜0.05）;DM组肝脏磷酸化腺苷酸活化蛋白激酶（p-AMPK）表达较NC组降低（P＜0.01）.结论 AMPK可能参与了肥胖及糖尿病大鼠NAFLD的发生发展.     

罗格列酮对老年胰岛素抵抗大鼠肝脏腺苷酸活化蛋白激酶α表达及活性的影响

目的 探讨罗格列酮(RGZ)对老年胰岛素抵抗(IR)大鼠肝脏脂肪酸代谢和腺苷酸活化蛋白激酶(AMPK)α表达及活性的影响. 方法 22～24月龄雄性Wistar大鼠随机分为老年对照(OC)组和高脂喂养组.4周后高脂喂养组IR状态形成,再随机分为高脂(HF)组和RGZ干预(RGZ)组,RGZ组予RGZ 3mg·kg~(-1)·d~(-1)灌胃,继续喂养4周.测定肝脏TG和AMPKα1、AMPKα2 mRNA表达,以及AMPKα1、AMPKα2、p-AMPKα蛋白表达. 结果 (1)HF组FPG、FIns、FFA、TC和TG高于OC组;而RGZ干预后这些指标均下降;葡萄糖输注率HF组低于OC组,RGZ组高于HF组(P<0.05或P<0.01).(2)肝脏TG HF组高于OC组,RGZ组低于HF组(P<0.01).(3)肝脏AMPKα1、AMPKα2mRNA表达和蛋白表达三组问无统计学差异(P>0.05);肝脏P-AMPKα蛋白表达HF组低于OC组,RGZ组高于HF组(P<0.05或P<0.01). 结论 高脂饮食导致老年大鼠肝脏脂肪酸代谢异常及IR;RGZ干预后AMPKα活性增加和肝脏脂质堆积减少,IR改善.     

α-硫辛酸对糖尿病大鼠下丘脑组织氧化应激及TRX-1、TXNIP的影响

目的探讨α-硫辛酸(LA)对糖尿病(DM)大鼠下丘脑组织氧化应激及TRX-1、硫氧还蛋白相互作用蛋白(TXNIP)的影响。方法将30只Wistar大鼠随机分为对照组10只、实验组20只。实验组20只用链脲佐菌素制备DM模型,建模成功后分为DM对照组(DC组)、LA干预组(LA组)各10只。对照组给予基础饲料喂养;D组、LA组给予高脂饮食,LA组给予LA干预4周。4周后用RT-PCR法检测各组下丘脑组织TRX-1、TXNIP mRNA表达;比色法检测丙二醛(MDA)、总抗氧化能力(T-AOC)。结果与对照组比较,DC组、LA组MDA、TRX-1mRNA、TXNIPmRNA明显升高,T-AOC明显降低(P<0.01或<0.05);与DC组比较,LA组MDA明显下降,T-AOC、TRX-1mRNA、TXNIP mRNA明显升高(P<0.01或<0.05)。结论 LA可改善DM大鼠的下丘脑氧化应激水平,提高其TRX-1、TXNIP mRNA表达水平。     

α-硫辛酸对2型糖尿病氧化应激状态和内皮功能的影响

目的观察α-硫辛酸对2型糖尿病患者氧化应激状态及血管内皮功能的影响。方法30例2型糖尿病患者每日给予α-硫辛酸600mg,治疗2周,检测治疗前后氧化还原系统指标、全血Na -K -ATP酶活力以及血流介导的内皮依赖性血管舒张功能。结果治疗后患者血清丙二醛含量降低、超氧化物歧化酶活力增高,差异有非常显著性(P<0.01),谷胱甘肽、维生素E含量增加,Na -K -ATP酶活力增强,血流介导的内皮依赖性的血管舒张功能增强,但差异无显著性(P>0.05),总体症状评分明显下降(P<0.01)。结论抗氧化剂α-硫辛酸治疗能改善2型糖尿病患者氧化应激状态及血管内皮功能,缓解临床症状。     

AMP活化蛋白激酶的抗氧化作用

AMP活化蛋白激酶(AMPK)广泛参与细胞代谢,在调节细胞能量代谢过程中起重要作用.另外,AMPK还可以调节机体抗氧化能力,通过调节机体抗氧化防御系统蛋白的表达,如硫氧化还原蛋白(TRX)、NAD(P)H氧化酶、二氧化锰超氧化物歧化酶(MnSOD)、过氧化物酶体增殖物活化受体协同刺激因子(PGC)-1α等,减少机体活性...     

腺苷酸活化蛋白激酶对糖脂代谢的影响

腺苷酸活化蛋白激酶 (AMPK)是一种重要的代谢应激蛋白激酶 ,在运动、缺氧等应激条件下可被高浓度的腺苷酸别构激活 ,AMPK一旦活化就可以使许多参与葡萄糖摄取和脂肪酸氧化的蛋白磷酸化 ,促进葡萄糖摄取 ,增加脂肪酸氧化 ,增加能量消耗 ,并且可以调控葡萄糖诱导基因的转录。 5 氨基 4 甲酰胺咪唑核糖核苷酸 (AICAR)是AMPK的非特异性激动剂 ,运动的急性效应 (增加骨骼肌葡萄糖摄取 )和慢性效应 (增加葡萄糖转运子 4 )都可以被AICAR所重复。AMPK可能在 2型糖尿病的运动治疗中发挥了重要作用。     

磷酸化腺苷酸活化蛋白激酶α在脂肪变性人肝癌HepG2细胞中的表达及其意义

目的观察腺苷酸活化蛋白激酶(AMPK)α磷酸化在Hep G2细胞脂变模型中的表达及意义。方法 Hep G2细胞予油酸和棕榈酸组成的0.3 mmol/L游离脂肪酸(FFA)诱导24 h后,建立脂肪变性Hep G2细胞模型,并设置对照组比较。诱导成功后,采用油红O染色观察细胞内脂滴蓄积状态;采用全自动生化仪检测细胞上清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)含量和细胞内甘油三酯(TG)含量;采用生物试剂盒检测细胞内超氧化物歧化酶(SOD)和丙二醛(MDA)含量的变化,运用Western印迹法检测各组细胞AMPKα和磷酸化AMPKα(p AMPKα)蛋白的表达。结果与对照组比较,模型组细胞内橘红色脂滴大量形成,且细胞内TG和MDA含量明显升高(P0.01),SOD含量水平明显下降(P0.01),p AMPKα蛋白表达均显著降低(P0.01)。结论 FFA诱导的脂肪变性Hep G2细胞模型可以出现脂质代谢紊乱和氧化应激状态,其机制可能与细胞内p AMPKα蛋白的激活减少有关。     

α-硫辛酸对糖尿病小鼠骨骼肌谷氨酰胺6磷酸果糖转氨酶1表达的影响

测定了四氧嘧啶制成的糖尿病小鼠模型骨骼肌的谷氨酰胺石磷酸果糖转氨酶1（GFATl）的mRNA表达水平。给予d硫辛酸治疗的糖尿病小鼠，骨骼肌内丙二醛水平低于不予治疗的糖尿病小鼠，而骨骼肌内GFAT-1的mRNA表达水平也低于不治疗组。     

2型糖尿病大鼠骨骼肌基因表达谱研究

用基因芯片技术比较2型糖尿病大鼠和正常大鼠骨骼肌基因表达谱的差异。糖尿病大鼠有157种基因下调，100种基因上调，部分基因与胰岛素抵抗、糖脂代谢相关。     

Effect of hyperglycemia on signal transduction in skeletal muscle from diabetic Goto-Kakizaki rats

We determined basal and insulin-stimulated responses on signaling intermediates in soleus skeletal muscle from male Wistar and diabetic Goto-Kakizaki (GK) rats. Rats were infused with glucose (5 or 20 mm) for 3 h, followed by a continuous infusion of saline or insulin (3 U/kg.h) for 20 min. Under euglycemic and hyperglycemic conditions, basal and insulin-stimulated action on phosphatidylinositol (PI) 3-kinase, protein kinase B/Akt, and ERK were reduced in GK rats, whereas insulin-stimulated protein kinase C (PKC)zeta activity was not altered. Interestingly, basal PKCzeta activity was increased under hyperglycemic conditions in GK and Wistar rats. This finding of increased PKCzeta activity was confirmed in vitro in isolated soleus muscle exposed to high extracellular glucose, and occurred concomitant with an increase in PI-dependent kinase 1 (PDK-1) activity. The glucose effects were not specific to PKCzeta, because an increase in phosphorylation of PKCalpha/beta and PKCdelta, but not PKCtheta, in isolated soleus muscle exposed to 25 mm glucose was observed. In conclusion, insulin signaling defects in diabetic GK rats are not corrected by an acute normalization of glycemia. Interestingly, acute hyperglycemia leads to a parallel increase in PDK-1, PKCalpha/beta, PKCdelta, and PKCzeta phosphorylation/activity via a PI 3-kinase-protein kinase B/Akt-independent mechanism. The long-term consequence of elevated PDK-1 and PKC phosphorylation/activity should be considered in the context of diabetes mellitus, as hyperglycemia is a clinical feature of this disease.     

The effect of alpha-lipoic acid on NOS dispersion in the lung of streptozotocin-induced diabetic rats

Oxidative stress and impaired bioactivity of nitric oxide (NO) play an important role in the organ pathogenesis and angiopathic complications of diabetes mellitus. In this study, we evaluated the effects of alpha-lipoic acid (ALA) on nitric oxide synthase (NOS) in lung tissues. ALA is a strong antioxidant. We wonder how it can affect oxidative stress and NO in the lung cells and vessels of diabetic rats. Wistar rats were divided into four groups; control, diabetic [65 mg/kg streptozotocin (STZ) for 15 days], STZ+ALA-treated (65 mg/kg ALA every 2 days for 15 days), and ALA-only-treated animals. At the end of the experimental period, lipid peroxidation, superoxide dismutase (SOD), and inducible NOS (iNOS) and endothelial NOS (eNOS) distribution were evaluated. Oxidative stress decreased with ALA in diabetic animals, and SOD also increased with ALA. iNOS and eNOS increased in diabetic animals, and ALA prevented iNOS increment in lung tissues. As a result, ALA can prevent some diabetic effects on the lungs and can also protect from vascular damages.     

神经生长因子对糖尿病大鼠运动终板和骨骼肌纤维的作用

外源性应用神经生长因子3个月有促进糖尿病大鼠脊髓前角运动神经元、运动终板、骨骼肌纤维的形态和功能恢复的作用。     

钒酸盐对糖尿病大鼠骨骼肌GLUT4基因表达的影响

观察钒酸欠对ＳＴＺ糖尿病大鼠糖代谢的影响地这一作用产生的机理进行了探讨。以０．５ｍｇ／ｍｌ钒酸钠溶液作为饮用水治疗三周后，糖尿病治疗组的血糖低于非治疗组３７．５％，但仍较正常组高。而骨骼肌中ＧＬＵＴ４ｍＲＮＡ含量较非治疗组高７３．８％，但仍代于正常组。     

Reduced alpha-lipoic acid synthase gene expression exacerbates atherosclerosis in diabetic apolipoprotein E-deficient mice

ObjectivesTo study the effects of reduced lipoic acid gene expression on diabetic atherosclerosis in apolipoprotein E null mice (Apoe^?/?).Methods and resultsHeterozygous lipoic acid synthase gene knockout mice (Lias^+/?) crossed with Apoe^?/? mice were used to evaluate the diabetic effect induced by streptozotocin on atherosclerosis in the aortic sinus of the heart. While diabetes markedly increased atherosclerotic plaque size in Apoe^?/? mice, a small but significant effect of reduced expression of lipoic acid gene was observed in diabetic Lias^+/?Apoe^?/? mice. In the aortic lesion area, the Lias^+/?Apoe^?/? mice exhibited significantly increased macrophage accumulation and cellular apoptosis than diabetic Lias^+/+Apoe^?/? littermates. Plasma glucose, cholesterol, and interleukin-6 were also higher. These abnormalities were accompanied with increased oxidative stress including a decreased ratio of reduced glutathione/oxidized glutathione in erythrocytes, increased systemic lipid peroxidation, and increased Gpx1 and MCP1 gene expression in the aorta.ConclusionsDecreased endogenous lipoic acid gene expression plays a role in development of diabetic atherosclerosis. These findings extend our understanding of the role of antioxidant in diabetic atherosclerosis.     

糖尿病大鼠骨骼肌的早期超微结构改变

链脲佐菌素复制的糖尿病大鼠在第4周和对照组相比，出现骨骼肌线粒体数目增加，线粒体变性、肿胀和排列紊乱。     

Effect of alpha-lipoic acid on lipid profile in rats fed a high-fructose diet

This study investigated the effect of administration of alpha-lipoic acid (LA) on lipid metabolism in high fructose-fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.