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Aim To explore the effeet of riboflavin on the establishment of pressure overload-induced heart failure model in mice by thoracic aortie constrietion (TAC ) and its preventive mechanism.Methods Eight-week-old SPF C57BL/6J mice were seleeted and divided into four groups; Sham group.Sham + ribofla¬vin group, TAC group and TAC + riboflavin group.A mouse heart failure model was constructed in the TAC group.The miee in the TAC + riboflavin group were given riboflavin by gavage one week before and eight weeks after the operation.The cardiac ultrasound inde¬xes, the changes of cardiac morphology and mitochon¬drial function indexes, the expression of apoptosis pro¬teins, ATP content, SCAD mRNA and protein expres¬sion, enzyme activity and flavin adenine dinucleotide (FAD) content in myocardial tissues were detected.Hie free fatty acid content in serum and myocardial tis¬sues were also detected.Results Compared with the sham group, the cardiac function indexes of the mice in the TAC group decreased, anrl typical heart failure occurred.Moreover, the expression of SCAD, enzyme activity, ATP and FAD content in the myocardium sig-nificantly decreased, and the free fatty acid content in myocardium and serum significantly increased.Com¬pared with the TAC group, after riboflavin treatment, the cardiac function of mice in TAC + Riboflavin group was significantly improved.In addition, ATP content, SCAD expression, enzyme activity and FAD content in myocardium all significantly increased, and free fatty acid content in myocardium and serum markedly de¬creased.Conclusions Riboflavin may improve myo-cardial energy metabolism by increasing FAD content and activating SCAD, thereby inhibiting pressure over¬load-induced heart failure in mice.
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OBJECTIVE:To explore the effects of acadesine on myocardial energy metabolism of model dogs with myocardial ischemia-reperfusion injury (MIRI) after cardiopulmonary bypass (CPB). METHODS:Dogs were randomly divided into control group,model group,acadesine low-dose,high-dose groups(0.8,3.2 mg/kg),6 in each group. All dogs received CPB. Except for control group,dogs in other groups were reduced for MIRI model,and perfused St.Thomas cardiac cardioplegia lipid containing rel-evant drugs 60 min after main artery block. The uptake rates of myocardial glucose and free fatty acid(FFA),creatine kinase isoen-zyme(CK-MB)concent in venous sinus plasma and adenosine triphosphate(ATP)content in mitochondria were detected and calcu-lated before bypass and after 15,60,90 min of reperfusion. Left ventricular systolic pressure(LVSP)and left ventricular end dia-stolic pressure(LVEDP)were analyzed,and mRNA expression of adenylate-activated protein kinase(AMPK)and protein expres-sion of phosphorylated AMPK(p-AMPK)in myocardial tissue were detected. RESULTS:Before bypass,all indexes in each group had no statistic significances(P>0.05). After bypass,compared with control group,uptake rates of myocardial glucose and FAA, ATP content,mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in model group and each administration group were obviously decreased(P<0.05);LVEDP and CK-MB concent in plasma were obviously increased(P<0.05). Compared with model group,uptake rates of myocardial glucose and FAA,ATP content,mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in each administration group were obviously increased (P<0.05);LVEDP and CK-MB concent in plasma were obviously decreased (P<0.05);and high-dose group showed more obvious change than that of low-dose group (P<0.05). CONCLUSIONS:Acadesine can promote the AMPK phosphorylation,contribute to the myocardial glucose and FFA uptake to promote the increase of ATP in myocardial mitochondria and relieve MIRI after CPB.
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OBJECTIVE:To explore the effects of acadesine on myocardial energy metabolism of model dogs with myocardial ischemia-reperfusion injury (MIRI) after cardiopulmonary bypass (CPB). METHODS:Dogs were randomly divided into control group,model group,acadesine low-dose,high-dose groups(0.8,3.2 mg/kg),6 in each group. All dogs received CPB. Except for control group,dogs in other groups were reduced for MIRI model,and perfused St.Thomas cardiac cardioplegia lipid containing rel-evant drugs 60 min after main artery block. The uptake rates of myocardial glucose and free fatty acid(FFA),creatine kinase isoen-zyme(CK-MB)concent in venous sinus plasma and adenosine triphosphate(ATP)content in mitochondria were detected and calcu-lated before bypass and after 15,60,90 min of reperfusion. Left ventricular systolic pressure(LVSP)and left ventricular end dia-stolic pressure(LVEDP)were analyzed,and mRNA expression of adenylate-activated protein kinase(AMPK)and protein expres-sion of phosphorylated AMPK(p-AMPK)in myocardial tissue were detected. RESULTS:Before bypass,all indexes in each group had no statistic significances(P>0.05). After bypass,compared with control group,uptake rates of myocardial glucose and FAA, ATP content,mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in model group and each administration group were obviously decreased(P<0.05);LVEDP and CK-MB concent in plasma were obviously increased(P<0.05). Compared with model group,uptake rates of myocardial glucose and FAA,ATP content,mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in each administration group were obviously increased (P<0.05);LVEDP and CK-MB concent in plasma were obviously decreased (P<0.05);and high-dose group showed more obvious change than that of low-dose group (P<0.05). CONCLUSIONS:Acadesine can promote the AMPK phosphorylation,contribute to the myocardial glucose and FFA uptake to promote the increase of ATP in myocardial mitochondria and relieve MIRI after CPB.
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Aim To further study the molecular mecha-nism of the herbs with hot nature on the regulational action on TRPV1 channel based on the 7900 Real-time PCR instrument. Methods 7900 PCR instrument was applied to detect the intracellular flurescence of TRPV1 channel in the dorsal root ganglions ( DRG ) neurons and the effect on the TRPV1 ’ s thermo-sensational functions of the selected 11 ingredients from hot herbs was explored. Results TRPV1 channels could be ac-tivated by gradually elevated temperature; the activa-tion process could be blocked by the TRPV1 specific blocking agent capsaizepine. Most of the ingredients from hot-nature herbs had the potential to up-regualate TRPV1 channel function. Conclusions The estab-lished TRPV1 channel detection system based on PCR instrument is suitable for the analysis of regulational functions of drugs on the heat-activated TRPV1 chan-nel;the functions of hot herbs may be related to the up-regualtional effects of its active ingredients on the TRPV1 channel which will further up-regulate energy metabolism.
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AIM:To investigate the effect of short-chain acyl-CoA dehydrogenase ( SCAD) on collagen expres-sion and proliferation of rat cardiac fibroblasts and to explore the relationship between SCAD and cardiac fibrosis . METHODS:The model of proliferation and collagen expression of rat cardiac fibroblasts induced by angiotensin II was es -tablished.After treatment with siRNA-1186, the expression of SCAD at mRNA and protein levels , fatty acids beta oxida-tion rate, ATP, the enzyme activity of SCAD and free fatty acids in the rat cardiac fibroblasts were determined . RESULTS:The mRNA and protein expression of SCAD was decreased in the rat cardiac fibroblasts induced by angiotensin II compared with the control cells , and the expression of collagen I and collagen III was significantly upregulated .Com-pared with negative control group , SCAD expression and activity , fatty acid beta-oxidation rate and ATP significantly de-creased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the rat cardiac fibroblasts , and the expression of collagen I and collagen III was significantly up-regulated.CONCLUSION:The expression and synthesis disorder of collagen may be triggered by down-regulation of SCAD .SCAD may be a promising therapeutic target for myocar-dial fibrosis .
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AIM:To investigate the change of short-chain acyl-CoA dehydrogenase (SCAD) expression during cardiomyocyte apoptosis and to explore the relationship between SCAD and cardiomyocyte apoptosis .METHODS: The neonatal rat cardiomyocytes treated by tert-butyl hydroperoxide (tBHP) were used as the model of cardiomyocyte apoptosis . The cell viability , the expression of SCAD at mRNA and protein levels , the activity of SCAD and the content of free fatty acids were determined .RESULTS:The mRNA and protein expression of SCAD decreased in the cardiomyocyte apoptosis model.Compared with negative control group , SCAD expression and activity were both significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the cardiomyocytes .Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP .CONCLUSION: Down-regulation of SCAD may play an important role in primary cardiomyocyte apoptosis .Increase in the expression of SCAD may become an impor-tant part in intervening cardiomyocyte apoptosis .