Dedifferentiated cardiomyocytes from chronic hibernating myocardium are ischemia-tolerant

Left ventricular biopsies from 21 patients with clinically diagnosed chronic hibernating myocardium (CHM) were examined by light- and electron microscopy. A mean of 27% of cardiomyocytes were structurally altered and were characterized as hibernating, because of reduced amount of myofibrils and increased glycogen content. Electron microscopy of these cells showed reduction of T-tubules and numerous small mitochondria, but few changes associated with degeneration, acute ischemia or apoptosis. The structural changes found in CHM are reminiscent of dedifferentiation rather than degeneration. The expression patterns of some structural proteins show resemblance with those in embryonic cardiomyocytes.Histochemically, mitochondrial NADH-oxidase and proton translocating ATPase activities were absent, whereas cytochrome c activity was present. Intracellular calcium distribution indicated normally bound sarcolemmal calcium and absence of excess mitochondrial calcium accumulation. Nuclear chromatin ranged from normal to dispersed with only a few nuclei that were clumped. These results suggest that cardiomyocytes from human CHM hearts are structurally altered, but viable, and lack morphologic and cytochemical characteristics suggestive of apoptosis or acute ischemia.     

Reduced sarcoplasmic reticulum Ca2+-ATPase activity and dephosphorylated phospholamban contribute to contractile dysfunction in human hibernating myocardium

Human hibernating myocardium (HHM) is characterized by reversible contractile dysfunction during chronic ischemia. A disturbed calcium-homeostasis is a decisive factor for reduced functional capacity in heart diseases. We therefore investigated calcium-handling proteins in HHM. In 12 patients suffering from multi-vessel coronary artery disease and contractile dysfunction with indication for bypass surgery, HHM was detected preoperatively by thallium scintigraphy, radionuclide ventriculography and dobutamine echocardiography. Transmural biopsies of these regions were taken and analyzed by immunohistochemistry and electron microscopy. Furthermore, SR-calcium ATPase (SERCA2a), phospholamban (PLN), the phosphorylated forms of PLN (PLN-Ser16, PLN-Thr17) as well as sodium-calcium exchanger (NCX) and ryanodine receptor (RyR2) were investigated by RT-PCR and Western-blotting. Additionally, SERCA2a activity was measured by an enzyme-coupled assay. In all patients complete functional recovery could be documented 3 months after revascularization by repeating all preoperative investigations. In HHM maximal SERCA2a activity was significantly reduced (HHM: 424.5± 33.9, control: 609.0± 48.5 nmol ATP mg protein⁻¹ min⁻¹, p≤ 0.05), whereas SERCA2a protein levels were unchanged. mRNA levels (HHM: 1.36± 0.08 vs. control: 0.78± 0.04, p≤ 0.05) and protein amount (HHM:1.67± 0.14 vs. control: 1.00± 0.04, p≤ 0.05) of PLN (A1) were increased resulting in an increased PLN:SERCA2a-ratio. PLN-Ser16 (HHM: 0.60± 0.08 vs. control: 1.00± 0.11, p≤ 0.05) and PLN-Thr17 (HHM: 0.63± 0.11 vs. control: 1.00± 0.06, p≤ 0.05) phosphorylation was significantly decreased. RyR2 and NCX showed no significant alteration. In HHM a decreased activity of SERCA2a due to an impaired phosphorylation of PLN contributes to contractile dysfunction. The increase in the relative ratio of PLN/SERCA2a leads to a decreased calcium affinity of SERCA2a.     

A self-perpetuating vicious cycle of tissue damage in human hibernating myocardium

Recently, we proposed the hypothesis that a vicious cycle exists in human hibernating myocardium (HM) between the progression of myocyte degeneration and the development of fibrosis [1]. We now investigated the pathomechanism of this cycle in more detail and established a correlation between the severity of the morphological changes and the degree of postoperative functional recovery of HM.HM was diagnosed by dobutamine echocardiography, thallium-201 scintigraphy and radionuclide ventriculography. Functional recovery was present at 3 months after coronary bypass surgery but remained unchanged at 15 months. Forty patients were subdivided into 2 groups: A with complete and B with incomplete recovery. Biopsies taken during surgery and studied by electron microscopy, immunocytochemistry, rt-PCR, and morphometry revealed myocyte degeneration and inflammatory and fibrinogenic changes in a widened interstitial space. We report here for the first time an upregulation of TGF-₁ evident by a 5-fold increase of fibroblasts and macrophages exhibiting a TGF-₁ content 3-fold larger than in control, and a > 3-fold increase in TGF-₁ mRNA by rt-PCR. The number of angiotensin converting enzyme (ACE) containing structures was increased (n/mm²: control - 11.4, A - 17.6, B - 19.2, control vs. A and B, p < 0.05). Fibrosis was more severe in group B than A or control (%: C - 10.1; A - 21.2; B - 40.6; p < 0.05). Capillary density was significantly reduced (n/mm²: C - 1152; A - 782; B - 579, p < 0.05) and intercapillary distance was widened (m: C - 29.5, A - 36.1, B - 43.3, p < 0.05). The number of CD 3 (n/mm²: C - 5.0; A - 9.6; B - 9.4, ns) and CD 68 positive cells (n/mm²: C - 37.2; A - 80.7; B - 55.0, C vs. A p < 0.05) was elevated in HM as compared to control indicating an inflammatory reaction. Cut-off points for functional recovery are fibrosis > 32%, capillary density < 660/mm² and intercapillary distance > 39.0 m.In HM a self-perpetuating vicious cycle of tissue alterations leads to progressive replacement fibrosis and continuous intracellular degeneration which should be interrupted by early revascularization.     

Effects of a low-voltage static electric field on energy metabolism in astrocytes

Mouse astrocytes (glial cells) in primary cultures were exposed to a low-voltage static DC electric field with no current flow and thus with no generation of magnetic fields. The electric field altered the rate of glycolysis, measured by 2-deoxyglucose accumulation. The magnitude and direction of this effect depended on the polarization of the field and the applied voltage. The maximum effect was an increase of ∼30%, which occurred with field across the cells at an intensity that can be calculated to be 0.3 mV/cm or less. Reversal of the polarization converted the stimulation to a small but statistically significant inhibition. Bioelectromagnetics 18:77–80, 1997. © 1997 Wiley-Liss, Inc.     

The changes in the energy metabolism of human muscle induced by training

The biochemical effects of training programmes have been studied with a kinetic model of central metabolism, using enzyme activities and metabolite concentrations measured at rest and after 30 s maximum-intensity exercise, collected before and after long and short periods of training, which differed only by the duration of the rest intervals. After short periods of training the glycolytic flux at rest was three times higher than it had been before training, whereas during exercise the flux and energy consumption remained the same as before training. Long periods of training had less effect on the glycolytic flux at rest, but increased it in response to exercise, increasing the contribution of oxidative phosphorylation.     

Alteration of energy production by the heart in CRF patients undergoing peritoneal dialysis

Cardiovascular disease is commonly observed in patients with chronic renal failure and this is a leading cause of death in patients with end-stage renal disease undergoing maintenance dialysis. Myocardial energy production is a very crucial aspect of cardiac function. Therefore, to evaluate energy metabolism of myocardial muscle in peritoneal dialysis (PD) patients, we carried out the following study using Magnetic resonance spectroscopy (MRS).Fourteen chronic renal failure patients and eight healthy volunteers were enrolled. The ratio of the phosphocreatine peak to the beta-phosphate to ATP peak (PCr/-ATP) was calculated from their MR spectra obtained by ³¹P-MR spectroscopy (Gyroscan S15, Philips). To determine the correlation between cardiac function and energy status, the left atrial diameter, the left ventricular (LV) end-diastolic diameter, the ejection fraction, the fraction of shortening and the LV mass index were measured by echocardiography. Peripheral blood sampling was also performed for creatinine, blood urea nitrogen, hematocrit, hemoglobin, ₂-microglobuline, intact parathyroid hormone.PCr/-ATP was significantly lower in PD (1.03 ± 0.15 vs. 1.40 ± 0.18: p = 0.0002), although all patients showed normal systolic function. No correlation was found between PCr/-ATP and cardiac function or hematological or biochemical markers. A negative correlation was present between PCr/-ATP and dialysis duration (r = 0.57, p < 0.05).Altered energy status of the myocardium in PD should be considered even if the patients did not show any systolic dysfunction. ³¹P-MRS is a useful tool to evaluate the energy status of the myocardium.     

Impairment of glucose metabolism and energy transfer in the hypertriglyceridemic rat heart

The metabolic pathways involved in ATP production in hypertriglyceridemic rat hearts were evaluated. Hearts from male Wistar rats with sugar-induced hypertriglyceridemia were perfused in an isolated organ system. Mechanical performance, oxygen uptake and beat rate were evaluated under perfusion with different oxidizable substrates. Age- and weight-matched animals were used as control. The hypertriglyceridemic (HTG) hearts showed a decrease in the mechanical work and slight diminution in the oxygen uptake when perfused with glucose, pyruvate or lactate. No differences were found when perfused with palmitate, octanoate or -hydroxybutyrate. The glycolytic flux in HTG hearts was 2.4 times lower than in control hearts. Phosphofructokinase-I (PFK-I) was 16% decreased in HTG hearts, whereas pyruvate kinase activity did not change. The increased levels of glucose-6hyphen;phosphate in HTG heart, suggested a flux limitation by the PFK-I. Pyruvate dehydrogenase in its active form (PDHa) diminished as well. The PDHa level in the HTG hearts was restored to control values by dichloroacetate; however, this addition did not significantly improve the mechanical performance. Levels of ATP and phosphocreatine as well as total creatine kinase activity and the MB fraction were significant lower in the HTG hearts perfused with glucose. The data suggested that supply of ATP by glucose oxidation did not suffice to support cardiac work in the HTG hearts; this impairment was exacerbated by the diminution of the creatine kinase system output.     

ATG7 regulates energy metabolism,differentiation and survival of Philadelphia-chromosome-positive cells

A major drawback of tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) is that primitive CML cells are able to survive TKI-mediated BCR-ABL inhibition, leading to disease persistence in patients. Investigation of strategies aiming to inhibit alternative survival pathways in CML is therefore critical. We have previously shown that a nonspecific pharmacological inhibition of autophagy potentiates TKI-induced death in Philadelphia chromosome-positive cells. Here we provide further understanding of how specific and pharmacological autophagy inhibition affects nonmitochondrial and mitochondrial energy metabolism and reactive oxygen species (ROS)-mediated differentiation of CML cells and highlight ATG7 (a critical component of the LC3 conjugation system) as a potential specific therapeutic target. By combining extra- and intracellular steady state metabolite measurements by liquid chromatography-mass spectrometry with metabolic flux assays using labeled glucose and functional assays, we demonstrate that knockdown of ATG7 results in decreased glycolysis and increased flux of labeled carbons through the mitochondrial tricarboxylic acid cycle. This leads to increased oxidative phosphorylation and mitochondrial ROS accumulation. Furthermore, following ROS accumulation, CML cells, including primary CML CD34⁺ progenitor cells, differentiate toward the erythroid lineage. Finally, ATG7 knockdown sensitizes CML progenitor cells to TKI-induced death, without affecting survival of normal cells, suggesting that specific inhibitors of ATG7 in combination with TKI would provide a novel therapeutic approach for CML patients exhibiting persistent disease.     

Effects of iloprost,a PGI2 derivative,on ischemic myocardial energy and carbohydrate metabolism in dogs

Effects of iloprost, which is a stable prostacyclin analogue, on the ischemic myocardium were examined in the open-chest dog heart, in terms of biochemical parameters. Ischemia was initiated by ligating the left anterior descending coronary artery. When the coronary artery was ligated for 3 min, the levels or glycogen, fructose-1,6-diphosphate (FDP), adenosine triphosphate and creatinephosphate decreased, and the levels of glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), lactate, adenosine diphosphate and adenosine monophosphate increased. During ischemia, therefore, energy charge potential was significantly decreased from 0.89±0.01 to 0.82±0.01, and ([G6P]+[F6P])/[FDP] and [lactate]/[pyruvate] ratios were significantly increased from 1.75±0.30 to 29.05±5.70 and 13±3 to 393±112, respectively. Iloprost (0.1, 0.3, or 1 g·kg^–1) was injected intravenously 5 min before the onset of ischemia. Iloprost (0.1, 0.3, and 1 g·kg^–1) reduced the ischemia-induced decrease in energy charge potential to 94, 74, and 86%, respectively, the increase in ([G6P]+[F6P]/[FDP] to 38, 29, 32%, respectively, and the increase in [lactate]/[pyruvate] to 67, 45, 65%, respectively. These results suggest that iloprost lessens the myocardial metabolic derangements produced by ischemia, and the most potent effect was obtained at the dose of 0.3 g·kg^–1.     

Lactate and glucose as energy substrates during, and after, oxygen deprivation in rat hippocampal acute and cultured slices

The effects of raised brain lactate levels on neuronal survival following hypoxia or ischemia is still a source of controversy among basic and clinical scientists. We have sought to address this controversy by studying the effects of glucose and lactate on neuronal survival in acute and cultured hippocampal slices. Following a 1-h hypoxic episode, neuronal survival in cultured hippocampal slices was significantly higher if glucose was present in the medium compared with lactate. However, when the energy substrate during the hypoxic period was glucose and then switched to lactate during the normoxic recovery period, the level of cell damage in the CA1 region of organotypic cultures was significantly improved from 64.3 +/- 2.1 to 74.6 +/- 2.1% compared with cultures receiving glucose during and after hypoxia. Extracellular field potentials recorded from the CA1 region of acute slices were abolished during oxygen deprivation for 20 min, but recovered almost fully to baseline levels with either glucose (82.6 +/- 10.0%) or lactate present in the reperfusion medium (108.1 +/- 8.3%). These results suggest that lactate alone cannot support neuronal survival during oxygen deprivation, but a combination of glucose followed by lactate provides for better neuroprotection than either substrate alone.     

Norepinephrine inhibits energy metabolism of human peripheral blood mononuclear cells via adrenergic receptors

Previous studies demonstrated that the adaptive response to stressors and inflammatory signals involves the activation of the automotic nervous system. Catecholamines have been shown to modulate the activity of various immune effector cells directly via membrane adrenergic receptors. Here, we investigated immediate effects of norepinephrine on energy metabolism of immune cells. Norepinephrine inhibits oxygen consumption of human peripheral blood mononuclear cells at concentrations that are relevant to its physiological range. The -adrenoreceptor antagonist propranolol, but not the -adrenoreceptor antagonist phentolamine reversed the norepinephrine induced inhibition in quiescent cells. Conversely, phentolamine but not propranolol is capable of blocking norepinephrine mediated effects in mitogen activated human peripheral blood mononuclear cells. Our data indicate that the sensitization of - and -adrenoreceptors on immune cells is differentially regulated, and that these processes depend on the activation state of these cells. These findings have important implications for the understanding of stress-induced suppression of immune function and may contribute to the elucidation of the pathogenesis of immunologically mediated diseases.     

Cerebral ischemia: Changes in brain choline,acetylcholine, and other monoamines as related to energy metabolism

The relationship of cerebral neurotransmitters acetylcholine (ACh), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT) to the energy state of the brain was examined in mice at various times following complete ischemia produced by decapitation, in gerbils submitted to transient global ischemia (10 min bilateral carotid artery occlusion, 5 or 30 min recirculation), and in rats 24 hr after irreversible microembolism. Ischemia caused significant reductions in brain monoamine concentrations. The alterations in NA, DA, and 5HT levels persisted during recirculation and were unrelated to energy restoration. They were accompanied by an increase in the concentrations of related metabolites, suggesting that synthesis was unable to compensate for the release of the transmitters at early post-ischemic time periods. As described for the catecholamines and 5HT, ischemia resulted in a significant decrease in ACh level, but recirculation was associated with a rapid increase in ACh concentration. Impaired synthesis and/or increased release of ACh can be responsible for the decrease in ACh concentration during ischemia. Early post-ischemic elevation of ACh may be related to the large increase in brain choline brought about by ischemia.     

Lipid Peroxidation, Tissue Necrosis, and Metabolic and Mechanical Recovery of Isolated Reperfused Rat Heart as a Function of Increasing Ischemia

Isolated Langendorff-perfused rat hearts, after 30 min of preperfusion, were submitted to increasing times of global normothermic ischemia (1, 2, 5, 10, 20 and 30 min) or to the same times of ischemia followed by 30 min of reperfusion. Analysis of malondialdehyde, ascorbic acid, oxypurines, nucleosides, nicotinic coen-zymes and high-energy phosphates was carried out by HPLC on neutralized perchloric acid extracts of freeze-clamped tissues. In addition, maximum rate of intra-ventricular pressure development and cardiac output of malondialdehyde, lactate dehydrogenase, oxypurines and nucleosides were monitored during both preperfusion and reperfusion. Besides decreasing energy metabolites and nicotinic coenzyme pool, prolonged ischemia produced oxidation of significant amounts of hypoxanthine and xanthine to uric acid and generation of detectable levels of malondialdehyde (0.002 μmollg dry weight). After oxygen and substrate readmission, tissue and perfusate malondialdehyde increased only if previous ischemia was longer than 5 min, while lactate dehydrogenase was detected in perfusate of reperfused hearts following 10, 20, and 30 min of ischemia. Highest values of tissue malondialdehyde and total malondialdehyde output were recorded in reperfused hearts subjected to 30 min of ischemia (0.043 μmol/g dry weight and 0.069 μmol/ 30 min/g dry weight, respectively). Since tissue malondialdehyde was observed without detectable lactate dehydrogenase release in perfusate, it might be stated that malondialdehyde generation (i.e., lipid peroxidation) temporally preceded lactate dehydrogenase release (i.e., tissue necrosis). In reperfused hearts, evaluation of myocardial energy state and of mechanical recovery allowed us to determine times of ischemia beyond which reperfusion did not positively affect these metabolic and functional parameters. Main findings are that, under these experimental conditions, lipid peroxidation might be the cause and not the consequence of tissue necrosis and that duration of ischemia might be the factor deciding effectiveness of reperfusion.     

Effect of changes in diet energy density on feed intake, milk yield and metabolic parameters in dairy cows in early lactation

The purpose of this experiment was to investigate how early lactating cows adjust their metabolism and production to acute, but moderate changes in the energy density of the diet. Sixty dairy cows were randomly assigned to one of four treatments: two change-over groups (HNH and NHN) and two control groups (HHH and NNN), where H and N refer to a high and normal energy density in the total mixed ration (TMR), respectively. The experimental period covered the first 9 weeks post calving, which was split up in three 3-week periods. Thus, cows assigned to HNH or NHN shifted TMR in weeks 4 and 7 after calving while cows assigned to HHH or NNN were fed the same TMR for all 9 weeks. Results from cows on treatment HNH were compared with group HHH while cows on treatment NHN were compared with group NNN. When the diet changed from N to H and H to N, cows increased and decreased their dry-matter intake (DMI), respectively compared with control groups. Cows adjusted milk yield accordingly to changes in DMI, although not always significantly. Energy-corrected milk yield was not significantly affected by any of the changes in the energy density of the diet but generally showed same tendencies as milk yield. Non-esterified fatty acids (NEFA), beta-hydroxybutyrate in blood and milk and triacylglycerol and glycogen content in the liver were not significantly affected by changes in the energy density of the diet, except from NEFA at one change. Glucose increased more when the diet changed from N to H and increased less when the diet changed from H to N, compared with control groups, although not always significantly. Collectively, these results suggest that cows adjust their DMI and partly milk yield according to the energy density of the diet and therefore only limited effects were observed in physiological parameters.     

Aspects of astrocyte energy metabolism,amino acid neurotransmitter homoeostasis and metabolic compartmentation

Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.     

Metabolic effects of TiO2 nanoparticles,a common component of sunscreens and cosmetics,on human keratinocytes

The long-term health risks of nanoparticles remain poorly understood, which is a serious concern given their prevalence in the environment from increased industrial and domestic use. The extent to which such compounds contribute to cellular toxicity is unclear, and although it is known that induction of oxidative stress pathways is associated with this process, the proteins and the metabolic pathways involved with nanoparticle-mediated oxidative stress and toxicity are largely unknown. To investigate this problem further, the effect of TiO₂ on the HaCaT human keratinocyte cell line was examined. The data show that although TiO₂ does not affect cell cycle phase distribution, nor cell death, these nanoparticles have a considerable and rapid effect on mitochondrial function. Metabolic analysis was performed to identify 268 metabolites of the specific pathways involved and 85 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. Importantly, the uptake of nanoparticles into the cultured cells was restricted to phagosomes, TiO₂ nanoparticles did not enter into the nucleus or any other cytoplasmic organelle. No other morphological changes were detected after 24-h exposure consistent with a specific role of mitochondria in this response.     

Effect of BCAA intake during endurance exercises on fatigue substances,muscle damage substances,and energy metabolism substances

The increase rate of utilization of branched-chain amino acids (BCAA) by muscle is reduced to its plasma concentration during prolonged exercise leading to glycogen. BCAA supplementation would reduce the serum activities of intramuscular enzymes associated with muscle damage. To examine the effects of BCAA administration on fatigue substances (serotonin, ammonia and lactate), muscle damage substances (CK and LDH) and energy metabolism substances (FFA and glucose) after endurance exercise. Subjects (n = 26, college-aged males) were randomly divided into an experimental (n = 13, EXP) and a placebo (n = 13, CON) group. Subjects both EXP and CON performed a bout of cycle training (70% VO₂max intensity) to exhaustion. Subject in the EXP were administrated BCAA (78ml/kg·w) prior to the bout of cycle exercise. Fatigue substances, muscle damage substances and energy metabolism substances were measured before ingesting BCAAs and placebos, 10 min before exercise, 30 min into exercise, immediately after exercise, and 30 min after exercise. Data were analyzed by two-way repeated measure ANCOVA, correlation and statistical significance was set at p < 0.05. The following results were obtained from this study; 1. In the change of fatigue substances : Serotonin in the EXP tended to decreased at the 10 min before exercise, 30 min into exercise, post exercise, and recovery 30 min. Serotonin in the CON was significantly greater than the EXP at the10 min before exercise and recovery 30. Ammonia in the EXP was increased at the 10 min before exercise, 30 min into exercise, and post exercise, but significantly decreased at the recovery 30min (p < 0.05). Ammonia in the CON was significantly lower than the EXP at the 10 min before exercise, 30 min into exercise, and post exercise (p < 0.05). Lactate in the EXP was significantly increased at the 30 min into exercise and significantly decreased at the post exercise and recovery 30 min. Lactate in the CON was significantly lower than the EXP at the post exercise (p < 0.05). 2. In the change of muscle damage substances : CK in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. CK in the CON was greater than the EXP. LDH in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. LDH in the CON was higher than the EXP. 3. In the change of energy metabolism substances :Glucose in the EXP tended to decrease at the 10 min before exercise, 30 min into exercise, post exercise and recovery 30 min. Glucose in the CON was significantly greater than the EXP at the recovery 30 min (p < .05). FFA in both EXP and CON was increased at the post exercise and recovery 30 min. % increase for FFA in the EXP was greater than the CON at the post exercise and recovery 30 min. 4. The relationship of the fatigue substances, muscle damage substances and energy metabolism substances after endurance exercise indicated strongly a positive relationship between LDH and ammonia and a negative relationship between LDH and FFA in the EXP. Also, there were a strong negative relationship between glucose and FFA and a positive relationship between glucose and serotonin in the EXP. There was a strong positive relationship between CK and LDH and a strong negative relationship between FFA and glucose in the CON. These results indicate that supplementary BCAA decreased serum concentrations of the intramuscular enzymes as CK and LDH following exhaustive exercise. This observation suggests that BCAA supplementation may reduce the muscle damage associated with endurance exercise.     

Intragastric administration of AMG517, a TRPV1 antagonist,enhanced activity-dependent energy metabolism via capsaicin-sensitive sensory nerves in mice

ABSTRACT

Transient receptor potential vanilloid 1 (TRPV1), a nociceptive cation channel, is known to play roles in regulating the energy metabolism (EM) of the whole body. We previously reported that TRPV1 antagonists such as AMG517 enhanced EM in mice, however, these mechanisms remain unclear. The aim of this study was to explore the mechanisms underlying the enhancement of EM by AMG517, a selective TRPV1 antagonist, in mice. Respiratory gas analysis indicated that intragastric administration of AMG517 enhanced EM along with increasing locomotor activity in mice. Next, to clarify the possible involvement with afferent sensory nerves, including the vagus, we desensitized the capsaicin-sensitive sensory nerves of mice by systemic capsaicin treatment. In the desensitized mice, intragastric administration of AMG517 did not change EM and locomotor activity. Therefore, this study indicated that intragastric administration of AMG517 enhanced EM and increased locomotor activity via capsaicin-sensitive sensory nerves, including vagal afferents in mice.     

长期异相睡眠剥夺对大鼠能量代谢及血清甲状腺素水平的影响

目的：探讨长期异相睡眠剥夺对大鼠能量代谢及血清甲状腺素水平的影响。方法：采用小平台水环境法建立长期异相睡眠剥夺大鼠模型;检测其能量代谢变化;放射免疫法检测血清中甲状腺素水平。结果：睡眠剥夺后大鼠摄食量由（75.06±25.37）g/（d.kg）增加到（122.30±20.43）g/（d.kg）,体重由（360.89±43.01）g减轻到（295.97±37.95）g,体温由（37.62±1.12）℃先升高到（39.00±0.87）℃后又降低至（37.72±0.84）℃,基础代谢率由（1.69±0.36）mlO2/（g.h）增加到（2.40±0.09）mlO2/（g.h）与对照组相比差异显著（P〈0.05）;血清中游离三碘甲状腺原氨酸（FT3）水平由（3.38±0.88）pmol/L降低到（2.38±0.83）pmol/L,游离甲状腺素（FT4）由（14.62±3.62）pmol/L降低到（8.26±2.80）pmol/L与对照组相比差异显著（P〈0.05）。结论：长期异相睡眠剥夺可以显著影响大鼠的能量代谢和血清甲状腺素水平。     

天津开发区滨海生态防护圈组成群落的生物量、物质和能量结构

构成天津开发区滨海生态防护圈的 4种群落的生物量和能量现存量分别为 ,乔 灌 草群落 2 8 5 5t·hm-2 、5 2 5 91× 10 9J·hm-2 ,灌木群落 2 8 11t·hm-2 、5 0 3 2 7× 10 9J·hm-2 ,草本群落 2 4 30t·hm-2 、35 5 6 8× 10 9J·hm-2 ,灌 草群落 4 2 1t·hm-2 、75 5 2× 10 9J·hm-2 ,都大大超过了原生植被碱蓬群落 ( 0 2 75t·hm-2 、3 6 1× 10 9J·hm-2 )。具有复层结构的乔 灌 草群落和灌 草群落在生物量和能量现存量的分配上 ,都是优势层占据绝对优势地位 ,而且在各群落中生物量和能量分配比例很接近 :乔 灌 草群落中乔木层占 84 34%和 84 4 3%、灌木层占14 89%和 14 84 %、草本层仅占 0 77%和 0 73% ;灌 草群落中灌木层占 80 0 8%和 80 5 1%、草本层占 19 95 %和 19 4 9%。 4种群落对N、P、K、Na、Ca、Mg、Cl- 7种元素的现存总量从大到小依次为草本群落 ( 2 4 81 87kg·hm-2 )、灌木群落 ( 5 18 16kg·hm-2 )、乔 灌 草群落 ( 4 99 4 9kg·hm-2 )、灌 草群落 ( 99 2 2kg·hm-2 ) ,大于原生碱蓬群落 ( 2 8 34kg·hm-2 )。草本群落对Na和Cl-有着极大的吸收和积累 ,分别达到 5 2 1 6 8kg·hm-2 和 14 2 9 15kg·hm-2 。元素现存量在复层结构的乔 灌 草群落和灌 草群落