Heart failure(HF)is a global public health problem with high morbidity and mortality.A large number of studies have shown that HF is caused by severe energy metabolism disorders,which result in an insufficient heart e...Heart failure(HF)is a global public health problem with high morbidity and mortality.A large number of studies have shown that HF is caused by severe energy metabolism disorders,which result in an insufficient heart energy supply.This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure,which determine the development of HF and recovery of heart.Current HF therapy acts by reducing heart rate and cardiac preload and afterload,treating the HF symptomatically or delaying development of the disease.Drugs aimed at cardiac energy metabolism have not yet been developed.In this review,we outline the main characteristics of cardiac energy metabolism in healthy hearts,changes in metabolism during HF,and related pathways and targets of energy metabolism.Finally,we discuss drugs that improve cardiac function via energy metabolism to provide new research ideas for the development and application of drugs for treating HF.展开更多
目的探讨磷酸肌酸钠对一次力竭运动大鼠心肌线粒体能量代谢变化的影响,探讨磷酸肌酸钠对应激心肌的保护机制。方法雄性Wistar大鼠36只,随机分为对照组(n=12)、一次力竭组(n=12)、磷酸肌酸钠组(n=12)。实验结束后测定各组心肌ATP含量及...目的探讨磷酸肌酸钠对一次力竭运动大鼠心肌线粒体能量代谢变化的影响,探讨磷酸肌酸钠对应激心肌的保护机制。方法雄性Wistar大鼠36只,随机分为对照组(n=12)、一次力竭组(n=12)、磷酸肌酸钠组(n=12)。实验结束后测定各组心肌ATP含量及血浆肾上腺素(E)、去甲肾上腺素(NE)、游离脂肪酸(FFA)浓度,并采用RT-PCR及Western blotting检测心肌线粒体解偶联蛋白2(UCP2)表达情况。结果与对照组相比,一次力竭组、磷酸肌酸钠组血浆FFA、E、NE浓度均增高(P<0.05),心肌ATP含量均降低。RT-PCR及Western blotting结果显示,一次力竭组、磷酸肌酸钠组UCP2 m RNA表达量分别较对照组增加64%、24%,UCP2蛋白表达量分别较对照组增加65%、26%。相关分析显示,心肌组织UCP2表达量与血浆FFA浓度呈显著正相关(r=0.98,P<0.01),血浆FFA浓度与血浆E、NE水平呈显著正相关(r=0.93,r=0.88,P<0.01)。结论力竭运动后心肌组织UCP2表达量显著上调,ATP合成减少,能量代谢障碍,可能是运动导致心源性猝死的机制之一。补充外源性磷酸肌酸钠可拮抗运动应激导致的UCP2表达升高,增加ATP储备,改善心肌能量代谢,可能对运动导致的心源性猝死预防有一定的积极作用。展开更多
Background:Shensong Yangxin Capsule (SSYX),traditional Chinese medicine,has been used to treat arrhythmias,angina,cardiac remodeling,cardiac fibrosis,and so on,but its effect on cardiac energy metabolism is still n...Background:Shensong Yangxin Capsule (SSYX),traditional Chinese medicine,has been used to treat arrhythmias,angina,cardiac remodeling,cardiac fibrosis,and so on,but its effect on cardiac energy metabolism is still not clear.The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) Ⅱ-induced cardiac hypertrophy.Methods:We used 2 μl (10-6 mol/L) AngⅡ to treat neonatal rat cardiomyocytes (NRCMs) for 48 h.Myocardial α-ac tinin staining showed that the myocardial cell volume increased.Expression of the cardiac hypertrophic marker-brain natriuretic peptide (BNP) messenger RNA (mRNA) also increased by real-time polymerase chain reaction (PCR).Therefore,it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed.Then,NRCMs were treated with 1 μl of different concentrations of SSYX (0.25,0.5,and 1.0 μg/ml) for another 24 h.To explore the time-depend effect of SSYX on energy metabolism,0.5 μg/ml SSYX was added into cells for 0,6,12,24,and 48 h.Mitochondria was assessed by MitoTracker staining and confocal microscopy.mRNA and protein expression of mitochondrial biogenesis-related genes-Peroxisome proliferator-activated receptor-γ coactivator-1 α (PGC-1 α),energy balance key factor -adenosine monophosphate-activated protein kinase (AMPK),fatty acids oxidation factor-camitine palmitoyltransferase-1 (CPT-1),and glucose oxidation factor-glucose transporter-4 (GLUT-4) were measured by PCR and Western blotting analysis.Results:With the increase in the concentration of SSYX (from 0.25 to 1.0 μg/ml),an increased mitochondrial density in Angll-induced cardiomyocytes was found compared to that of those treated with Angll only (0.25 μg/ml,18.3300 ± 0.8895 vs.24.4900 ± 0.9041,t =10.240,P 〈 0.0001;0.5 μg/ml,18.3300 ± 0.8895 vs.25.9800 ± 0.8187,t =12.710,P 〈 0.0001;and 1.0 μg/ml,18.3300 ± 0.8895 vs.24.2900 ± 1.3120,t =9.902,P 〈 0.0001;n =5 per dosage group)展开更多
Ginseng, the root of Panax ginseng C. A. Mayer, has long been used clinically in China to treat various diseases. Multiple effects of ginseng, such as antitumor, antiinflammatory, antiallergic, antioxidative, antidiab...Ginseng, the root of Panax ginseng C. A. Mayer, has long been used clinically in China to treat various diseases. Multiple effects of ginseng, such as antitumor, antiinflammatory, antiallergic, antioxidative, antidiabetic and antihypertensive have been confirmed by modern medicine. Recently, the clinical utilization of ginseng to treat heart diseases has increased dramatically. The roles of ginseng in protecting heart are foci for research in modern medical science and have been partially demonstrated, and the mechanisms of protection against coronary artery disease, cardiac hypertrophy, heart failure, cardiac energy metabolism, cardiac contractility, and arrhythmia are being uncovered progressively. However, more studies are needed to elucidate the complex mechanisms by which ginseng protects heart. All such studies will provide evidence of ginseng's clinical application, international promotion, and new drug development.展开更多
Background: Shen-Fu injection (SFI) can attenuate ischemia-reperfusion injury, protect cardiac function, and improve microcirculation during cardiopulmonary resuscitation. We hypothesized that SFI may also have an ...Background: Shen-Fu injection (SFI) can attenuate ischemia-reperfusion injury, protect cardiac function, and improve microcirculation during cardiopulmonary resuscitation. We hypothesized that SFI may also have an influence on myocardial metabolism during ventrictdar fibrillation (VF). In this study, we used SFI pretreatment prior to VF to discuss the changes of myocardial metabolism and catecholamine (CA) levels during untreated VF, trying to provide new evidence to the protection of SFI to myocardiurn. Methods: Twenty-four pigs were divided into three groups: Saline group (SA group), SFI group, and SHAM operation group (SHAM group). Thirty minutes prior to the induction of VF, the SFI group received 0.24 mg/ml SFI through an intravenous injection: the SA group received an equal amount of sodium chloride solution. The interstitial fluid from the left ventricle (LV) wall was collected through the microdialysis tubes during VF. Adenosine diphosphate (ADP), adenosine triphosphate (ATP), and Na^+-K^+-ATPase and Ca2^+-ATPase enzyme activities were measured after untreated VF. Peak-to-trough VF amplitude and median frequency were analyzed for each of these 5-s intervals. Results: The levels of glucose and glutamate were lower after VF in both the SA and SFI groups, compared with baseline, and the levels in the SFI group were higher than those in the SA group. Compared with baseline, the levels of lactate and the lactate/pyruvate ratio increased after VF in both SA and SFI groups, and the levels in the SFI group were lower than those in the SA group. In both the SA and SFI groups, the levers of dopamine, norepinephrine, and epinephrine increased significantly. There were no statistical differences between the two groups. The content of ATE ADE and phosphocreatine in the SF1 group was higher than those in the SA group. The activity ofLV Na^+-K^+-ATPase was significantly higher in the SFI group than in the SA group. Amplitude mean spectrum area (AMSA) was significan展开更多
基金support of National Key Research and Development Program(2018YFC1707205,China)Sichuan Provincial Administration of Traditional Chinese Medicine Research Project(2018NQ008,China)。
文摘Heart failure(HF)is a global public health problem with high morbidity and mortality.A large number of studies have shown that HF is caused by severe energy metabolism disorders,which result in an insufficient heart energy supply.This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure,which determine the development of HF and recovery of heart.Current HF therapy acts by reducing heart rate and cardiac preload and afterload,treating the HF symptomatically or delaying development of the disease.Drugs aimed at cardiac energy metabolism have not yet been developed.In this review,we outline the main characteristics of cardiac energy metabolism in healthy hearts,changes in metabolism during HF,and related pathways and targets of energy metabolism.Finally,we discuss drugs that improve cardiac function via energy metabolism to provide new research ideas for the development and application of drugs for treating HF.
文摘目的探讨磷酸肌酸钠对一次力竭运动大鼠心肌线粒体能量代谢变化的影响,探讨磷酸肌酸钠对应激心肌的保护机制。方法雄性Wistar大鼠36只,随机分为对照组(n=12)、一次力竭组(n=12)、磷酸肌酸钠组(n=12)。实验结束后测定各组心肌ATP含量及血浆肾上腺素(E)、去甲肾上腺素(NE)、游离脂肪酸(FFA)浓度,并采用RT-PCR及Western blotting检测心肌线粒体解偶联蛋白2(UCP2)表达情况。结果与对照组相比,一次力竭组、磷酸肌酸钠组血浆FFA、E、NE浓度均增高(P<0.05),心肌ATP含量均降低。RT-PCR及Western blotting结果显示,一次力竭组、磷酸肌酸钠组UCP2 m RNA表达量分别较对照组增加64%、24%,UCP2蛋白表达量分别较对照组增加65%、26%。相关分析显示,心肌组织UCP2表达量与血浆FFA浓度呈显著正相关(r=0.98,P<0.01),血浆FFA浓度与血浆E、NE水平呈显著正相关(r=0.93,r=0.88,P<0.01)。结论力竭运动后心肌组织UCP2表达量显著上调,ATP合成减少,能量代谢障碍,可能是运动导致心源性猝死的机制之一。补充外源性磷酸肌酸钠可拮抗运动应激导致的UCP2表达升高,增加ATP储备,改善心肌能量代谢,可能对运动导致的心源性猝死预防有一定的积极作用。
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 81670363).
文摘Background:Shensong Yangxin Capsule (SSYX),traditional Chinese medicine,has been used to treat arrhythmias,angina,cardiac remodeling,cardiac fibrosis,and so on,but its effect on cardiac energy metabolism is still not clear.The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) Ⅱ-induced cardiac hypertrophy.Methods:We used 2 μl (10-6 mol/L) AngⅡ to treat neonatal rat cardiomyocytes (NRCMs) for 48 h.Myocardial α-ac tinin staining showed that the myocardial cell volume increased.Expression of the cardiac hypertrophic marker-brain natriuretic peptide (BNP) messenger RNA (mRNA) also increased by real-time polymerase chain reaction (PCR).Therefore,it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed.Then,NRCMs were treated with 1 μl of different concentrations of SSYX (0.25,0.5,and 1.0 μg/ml) for another 24 h.To explore the time-depend effect of SSYX on energy metabolism,0.5 μg/ml SSYX was added into cells for 0,6,12,24,and 48 h.Mitochondria was assessed by MitoTracker staining and confocal microscopy.mRNA and protein expression of mitochondrial biogenesis-related genes-Peroxisome proliferator-activated receptor-γ coactivator-1 α (PGC-1 α),energy balance key factor -adenosine monophosphate-activated protein kinase (AMPK),fatty acids oxidation factor-camitine palmitoyltransferase-1 (CPT-1),and glucose oxidation factor-glucose transporter-4 (GLUT-4) were measured by PCR and Western blotting analysis.Results:With the increase in the concentration of SSYX (from 0.25 to 1.0 μg/ml),an increased mitochondrial density in Angll-induced cardiomyocytes was found compared to that of those treated with Angll only (0.25 μg/ml,18.3300 ± 0.8895 vs.24.4900 ± 0.9041,t =10.240,P 〈 0.0001;0.5 μg/ml,18.3300 ± 0.8895 vs.25.9800 ± 0.8187,t =12.710,P 〈 0.0001;and 1.0 μg/ml,18.3300 ± 0.8895 vs.24.2900 ± 1.3120,t =9.902,P 〈 0.0001;n =5 per dosage group)
基金Supported by National Natural Science Foundation of China (No.81173367 and No.30873234)Beijing Key Disciplines Project of Traditional Chinese Medicine(No.JZZ-312)
文摘Ginseng, the root of Panax ginseng C. A. Mayer, has long been used clinically in China to treat various diseases. Multiple effects of ginseng, such as antitumor, antiinflammatory, antiallergic, antioxidative, antidiabetic and antihypertensive have been confirmed by modern medicine. Recently, the clinical utilization of ginseng to treat heart diseases has increased dramatically. The roles of ginseng in protecting heart are foci for research in modern medical science and have been partially demonstrated, and the mechanisms of protection against coronary artery disease, cardiac hypertrophy, heart failure, cardiac energy metabolism, cardiac contractility, and arrhythmia are being uncovered progressively. However, more studies are needed to elucidate the complex mechanisms by which ginseng protects heart. All such studies will provide evidence of ginseng's clinical application, international promotion, and new drug development.
基金This work was supported b-y grants from the National Natural Science Foundation of China (No. 81372025) and the Beijing Natural Science Foundation (No. 7132092).
文摘Background: Shen-Fu injection (SFI) can attenuate ischemia-reperfusion injury, protect cardiac function, and improve microcirculation during cardiopulmonary resuscitation. We hypothesized that SFI may also have an influence on myocardial metabolism during ventrictdar fibrillation (VF). In this study, we used SFI pretreatment prior to VF to discuss the changes of myocardial metabolism and catecholamine (CA) levels during untreated VF, trying to provide new evidence to the protection of SFI to myocardiurn. Methods: Twenty-four pigs were divided into three groups: Saline group (SA group), SFI group, and SHAM operation group (SHAM group). Thirty minutes prior to the induction of VF, the SFI group received 0.24 mg/ml SFI through an intravenous injection: the SA group received an equal amount of sodium chloride solution. The interstitial fluid from the left ventricle (LV) wall was collected through the microdialysis tubes during VF. Adenosine diphosphate (ADP), adenosine triphosphate (ATP), and Na^+-K^+-ATPase and Ca2^+-ATPase enzyme activities were measured after untreated VF. Peak-to-trough VF amplitude and median frequency were analyzed for each of these 5-s intervals. Results: The levels of glucose and glutamate were lower after VF in both the SA and SFI groups, compared with baseline, and the levels in the SFI group were higher than those in the SA group. Compared with baseline, the levels of lactate and the lactate/pyruvate ratio increased after VF in both SA and SFI groups, and the levels in the SFI group were lower than those in the SA group. In both the SA and SFI groups, the levers of dopamine, norepinephrine, and epinephrine increased significantly. There were no statistical differences between the two groups. The content of ATE ADE and phosphocreatine in the SF1 group was higher than those in the SA group. The activity ofLV Na^+-K^+-ATPase was significantly higher in the SFI group than in the SA group. Amplitude mean spectrum area (AMSA) was significan