The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE ...The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.展开更多
SIRT1,a mammalian ortholog of yeast silent information regulator 2(Sir2),is an NAD+-dependent protein deacetylase that plays a critical role in the regulation of vascular function.The current study aims to investigate...SIRT1,a mammalian ortholog of yeast silent information regulator 2(Sir2),is an NAD+-dependent protein deacetylase that plays a critical role in the regulation of vascular function.The current study aims to investigate the functional significance of deacetylase activity of SIRT1 in heart.Here we show that the early postnatal hearts expressed the highest level of SIRT1deacetylase activity compared to adult and aged hearts.We generated transgenic mice with cardiac-specific expression of a dominant-negative form of the human SIRT1(SIRT1H363Y),which represses endogenous SIRT1 activity.The transgenic mice displayed dilated atrial and ventricular chambers,and died early in the postnatal period.Pathological,echocardiographic and molecular phenotype confirmed the presence of dilated cardiomyopathy.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling analysis revealed a greater abundance of apoptotic nuclei in the hearts of transgenic mice.Furthermore,we show that cardiomyocyte apoptosis caused by suppression of SIRT1 activity is,at least in part,due to increased p53acetylation and upregulated Bax expression.These results indicate that dominant negative form of SIRT1(SIRT1H363Y)overexpression in mouse hearts causes cardiomyocyte apoptosis and early-onset heart failure,suggesting a critical role of SIRT1 in preserving normal cardiac development during the early postnatal period.展开更多
OBJECTIVE: To investigate the effect of Lingguizhugan decoction (LGZGD) on changes of cardiac structure and function, and its putative mechanism of action, by investigating mRNA and protein expression of myocardial nu...OBJECTIVE: To investigate the effect of Lingguizhugan decoction (LGZGD) on changes of cardiac structure and function, and its putative mechanism of action, by investigating mRNA and protein expression of myocardial nuclear factor kappa B(NF-κB), and the plasma content of NF-κB in rats with chronic heart failure.METHODS: The chronic heart failure (CHF) model in rats was induced by coronary artery ligation.Sham operation was performed in control rats. Six weeks after the procedure, rats were randomly classified into the various treatment groups: model CHF, Captopril (4.4 mg/kg), low LGZGD dose (2.1 g/kg), medium LGZGD dose (4.2 g/kg), and high LG-ZGD dose (8.4 g/kg). Treatments continued for 4 consecutive weeks. Changes of hemodynamic indices were observed by the PowerLab data acquisition and analysis system. Morphological changes of myocardium were observed by hematoxylin and eosin staining, and Masson staining. The mRNA and protein expression of myocardial NF-κB were detected by reverse transcription-polymerase chain reaction and western blotting, respectively. The plasma content of NF-κB was detected by enzyme-linked immuno-sorbent assay.RESULTS: CHF rats showed significant dysfunction in hemodynamic indices and in cardiac structure.Compared with the sham operation group, mRNA expression of myocardial NF-κB and plasma content of NF-κB of the model group was significantly increased. All three doses of LGZGD, and Captopril,improved the hemodynamic dysfunction, and inhibited the change of cardiac structure while significantly improving the survival rate. Furthermore,compared with the model group, mRNA expression of myocardial NF-κB and plasma content of NF-κB were significantly reduced by all dosage groups of LGZGD as well as the\Captopril group.CONCLUSION: In CHF rats, LGZGD improves changes of cardiac structure and function via its inhibition of NF-κB.展开更多
OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divide...OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divided into six groups (n=10) as follows: (a) propranolol dinitrate control group, given propranolol dinitrate 0.02 g/kg for 10 days before I/R, (b) SWTX with a high dose group, given SWTX 1.5 g/kg for 10 days before I/R, (c) SWTX with a medium dose group, given SWTX 1.25 g/kg for 10 days before I/R, (d) sham group (Sham), in which the rat heart was exposed by pericardiotomy but without I/R, (e) SWTX with a low dose group, given SWTX 1.0 g/kg for 10 days before I/R, and (f) I/R injury group. Rats were intragastrically pretreated with propranolol dinitrate orSWTX. After that, the operation to cause ischemia and reperfusion was conducted.The histopathologic changes of rat hearts were observed by hematoxylin and eosin staining and transmission electron microscopy. Ca2+ homeostasis protein expression was determined by western blot. RESULTS: After SWTX pretreatment, the development of ultrastructural pathological changes from IR injury was attenuated. A decrease in the expression of B-cell lymphoma 2 associated X protein, and an increase in the expression of B-cell lymphoma 2 were observed. An increased activation of extracellular signal regulated kinases were found. Compared with the sham group, the expression of sarcoplasmic reticulum calcium-ATPase, phospholamban, and calsequestrin were all up-regulated after pretreatment with SWTX. CONCLUSION: The protective mechanism of SWTX pretreatment on myocardial I/R injury might be related to its effect on maintaining the balance of calcium homeostasis in rat heart.展开更多
文摘The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.
基金supported by the National Natural Science Foundation of China(31271227,81161120551)the National Basic Research Program of China(2011CB503902)
文摘SIRT1,a mammalian ortholog of yeast silent information regulator 2(Sir2),is an NAD+-dependent protein deacetylase that plays a critical role in the regulation of vascular function.The current study aims to investigate the functional significance of deacetylase activity of SIRT1 in heart.Here we show that the early postnatal hearts expressed the highest level of SIRT1deacetylase activity compared to adult and aged hearts.We generated transgenic mice with cardiac-specific expression of a dominant-negative form of the human SIRT1(SIRT1H363Y),which represses endogenous SIRT1 activity.The transgenic mice displayed dilated atrial and ventricular chambers,and died early in the postnatal period.Pathological,echocardiographic and molecular phenotype confirmed the presence of dilated cardiomyopathy.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling analysis revealed a greater abundance of apoptotic nuclei in the hearts of transgenic mice.Furthermore,we show that cardiomyocyte apoptosis caused by suppression of SIRT1 activity is,at least in part,due to increased p53acetylation and upregulated Bax expression.These results indicate that dominant negative form of SIRT1(SIRT1H363Y)overexpression in mouse hearts causes cardiomyocyte apoptosis and early-onset heart failure,suggesting a critical role of SIRT1 in preserving normal cardiac development during the early postnatal period.
基金Supported by the National Natural Science Fund of China(No.30973707)National Natural Science Fund of China Youth Project(No.81202631)+1 种基金Natural Science Fund of Anhui Province(No.070413262X)Anhui Provincial Science and Technology Projects (No.10021303024)
文摘OBJECTIVE: To investigate the effect of Lingguizhugan decoction (LGZGD) on changes of cardiac structure and function, and its putative mechanism of action, by investigating mRNA and protein expression of myocardial nuclear factor kappa B(NF-κB), and the plasma content of NF-κB in rats with chronic heart failure.METHODS: The chronic heart failure (CHF) model in rats was induced by coronary artery ligation.Sham operation was performed in control rats. Six weeks after the procedure, rats were randomly classified into the various treatment groups: model CHF, Captopril (4.4 mg/kg), low LGZGD dose (2.1 g/kg), medium LGZGD dose (4.2 g/kg), and high LG-ZGD dose (8.4 g/kg). Treatments continued for 4 consecutive weeks. Changes of hemodynamic indices were observed by the PowerLab data acquisition and analysis system. Morphological changes of myocardium were observed by hematoxylin and eosin staining, and Masson staining. The mRNA and protein expression of myocardial NF-κB were detected by reverse transcription-polymerase chain reaction and western blotting, respectively. The plasma content of NF-κB was detected by enzyme-linked immuno-sorbent assay.RESULTS: CHF rats showed significant dysfunction in hemodynamic indices and in cardiac structure.Compared with the sham operation group, mRNA expression of myocardial NF-κB and plasma content of NF-κB of the model group was significantly increased. All three doses of LGZGD, and Captopril,improved the hemodynamic dysfunction, and inhibited the change of cardiac structure while significantly improving the survival rate. Furthermore,compared with the model group, mRNA expression of myocardial NF-κB and plasma content of NF-κB were significantly reduced by all dosage groups of LGZGD as well as the\Captopril group.CONCLUSION: In CHF rats, LGZGD improves changes of cardiac structure and function via its inhibition of NF-κB.
基金Supported by a Grant from the National Natural Sciences Foundation of China(No.81060368)
文摘OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divided into six groups (n=10) as follows: (a) propranolol dinitrate control group, given propranolol dinitrate 0.02 g/kg for 10 days before I/R, (b) SWTX with a high dose group, given SWTX 1.5 g/kg for 10 days before I/R, (c) SWTX with a medium dose group, given SWTX 1.25 g/kg for 10 days before I/R, (d) sham group (Sham), in which the rat heart was exposed by pericardiotomy but without I/R, (e) SWTX with a low dose group, given SWTX 1.0 g/kg for 10 days before I/R, and (f) I/R injury group. Rats were intragastrically pretreated with propranolol dinitrate orSWTX. After that, the operation to cause ischemia and reperfusion was conducted.The histopathologic changes of rat hearts were observed by hematoxylin and eosin staining and transmission electron microscopy. Ca2+ homeostasis protein expression was determined by western blot. RESULTS: After SWTX pretreatment, the development of ultrastructural pathological changes from IR injury was attenuated. A decrease in the expression of B-cell lymphoma 2 associated X protein, and an increase in the expression of B-cell lymphoma 2 were observed. An increased activation of extracellular signal regulated kinases were found. Compared with the sham group, the expression of sarcoplasmic reticulum calcium-ATPase, phospholamban, and calsequestrin were all up-regulated after pretreatment with SWTX. CONCLUSION: The protective mechanism of SWTX pretreatment on myocardial I/R injury might be related to its effect on maintaining the balance of calcium homeostasis in rat heart.
