摘要
Aim To investigate the inotropic effect of PF-04957325, a phosphodiesterase type 8 inhibitor, in normal rats and its underlying molecular mechanism. Methods The techniques of in vivo rat left ventricular pressure-volume loop (P-V loop) and isolated perfusion rat heart were used to analyze the hemodynamics and positive inotropic effect of rat hearts. The Ca transient induced by field stimulation was used to analyze the hemodynamics of sarcoplasmic reticulum (SR) Ca + uptaking. Western blot was used to analyze the phosphorylation levels of SR phospolamban (PLB) and ryanodine receptor type 2 (RyR2). Results The P-V loop experiment indicated that PF-04957325 (0.5 mg · kg
摘要
Heart failure from various cardiovascular diseases is a serious threat to human health. Systolic and diastolic dysfunction are the basic characteristics of heart failure. SERCA2a, a key enzyme for calcium transport, regulates intracellular free calcium ion concentration, affecting the myocardial diastolic process. This article mainly summarized the structure and function of SERCA2a gene, the expression and regulation of SERCA2a in heart failure, and the current situation of drug therapy, gene therapy and clinical research targeting SERCA2a gene.
摘要
Objective To investigate the effect and mechanism of recombinant adenovirus associated vi-rus type 1 (rAAV1) mediated SERCA2a gene transfer on cardiac function in canine with heart failure (HF). Methods 20 healthy male beagle dogs were randomly divided into control group,HF group,HF+EGFP group and HF+SERCA2a group,5 dogs in each group. The canine cardiac function,apoptosis and MMP-9 expression in cardiac myocytes were detected by TUNEL and immunohistochemistry methods. Results The left ventricular dia-stolic diameter (LVDD),left ventricular systolic diameter (LVSD) and left ventricular posterior wall dimension (LVPWD)in the HF and HF+EGFP groups,were significantly higher than those of the control and HF+SERCA2a groups,and the ejection fraction(EF)in the former two groups was significantly lower than that of the control group and HF+SERCA2a group(P<0.05). The left ventricular systolic pressure(LVSP)and left ventricular maximal rate of pressure rise(+dp/dtmax)in the HF and HF+EGFP groups were both significantly lower than those of the control group and HF+SERCA2a group,while left ventricular end diastolic pressure(LVEDP)and left ventricular maximal rate of pressure decline(-dp/dtmax)significantly higher than those of the control and HF+SERCA2a groups(P<0.05). The apoptosis index of HF+SERCA2a group was significantly lower than that of group HF and group HF+EGFP(P<0.05). The MMP-9 light density of HF+SERCA2a group was significantly higher than that of the control group(P < 0.05). Conclusion RAAV1 mediated CA2a SER gene transfer can effectively improve the cardiac function of HF dog,probably by inhibiting the apoptosis of cardiac muscle cells and down-regulating the expression of MMP-9.
摘要
Objective To investigate the effect and mechanism of recombinant adenovirus associated vi-rus type 1 (rAAV1) mediated SERCA2a gene transfer on cardiac function in canine with heart failure (HF). Methods 20 healthy male beagle dogs were randomly divided into control group,HF group,HF+EGFP group and HF+SERCA2a group,5 dogs in each group. The canine cardiac function,apoptosis and MMP-9 expression in cardiac myocytes were detected by TUNEL and immunohistochemistry methods. Results The left ventricular dia-stolic diameter (LVDD),left ventricular systolic diameter (LVSD) and left ventricular posterior wall dimension (LVPWD)in the HF and HF+EGFP groups,were significantly higher than those of the control and HF+SERCA2a groups,and the ejection fraction(EF)in the former two groups was significantly lower than that of the control group and HF+SERCA2a group(P<0.05). The left ventricular systolic pressure(LVSP)and left ventricular maximal rate of pressure rise(+dp/dtmax)in the HF and HF+EGFP groups were both significantly lower than those of the control group and HF+SERCA2a group,while left ventricular end diastolic pressure(LVEDP)and left ventricular maximal rate of pressure decline(-dp/dtmax)significantly higher than those of the control and HF+SERCA2a groups(P<0.05). The apoptosis index of HF+SERCA2a group was significantly lower than that of group HF and group HF+EGFP(P<0.05). The MMP-9 light density of HF+SERCA2a group was significantly higher than that of the control group(P < 0.05). Conclusion RAAV1 mediated CA2a SER gene transfer can effectively improve the cardiac function of HF dog,probably by inhibiting the apoptosis of cardiac muscle cells and down-regulating the expression of MMP-9.
摘要
Objective To observe the abnormity of heart function in rats with pressure overload-induced left ventricular hypertrophy and the changes of NCX,SERCA2a expression in myocardial tissues. Methods Cardiac hypertrophy was induced by clipping the abdominal aorta in rats. The cardiac hypertrophy was evaluated by Left ventricular weight index(LVWI,left ventricular weight/body weight). NCX, SERCA2a mRNA and protein expressions in left ventricular tissues were determined by half-quantitative RT-PCR and Western blot normalized to abundance of GAPDH mRNA and protein,respectively. Results LVSP and LVEDP were obviously enhanced(P