Study on the effect of doxorubicin on expressions of genes encoding myocardial sarcoplasmic reticulum Ca~(2+) transport proteins and the effect of taurine on myocardial protection in rabbits

摘要

To investigate the effect of doxorubicin(DOX) on gene expression of the myocardial sarcoplasmic reticulum (SR)Ca~(2+) transport proteins and the mechanism of taurine(Tau) protecting cardiac muscle cells, 9 rabbits were injected with DOX , 8 rabbits with DOX and Tau, and 9 rabbits with normal saline. Cardiac function, concentration of calcium in cardiomyocytes ( Myo [ Ca~(2+) ]_i ), activity of SR Ca~(2+) -ATPase (SERCA2a), level of SERCA2a mRNA and Ca~(2+) released channels(RYR2) mRNA were detected. The left ventricle tissues were observed by electron microscopy. The results showed that cardiac index, left ventricular systolic pressure, activity of SR Ca~(2+) -ATPase and level of SERCA2a mRNA decreased, while Myo[Ca~(2+)]_i increased in DOX-treated rabbits. DOX could not affect the level of RYR2 mRNA. Tau intervention could alleviate the increase of left ventricular diastolic pressure, Myo [ Ca~(2+)]_i and the decrease of SERCA2a mRNA induced by doxorubicin. The results suggested that downregulation of SERCA2a gene expression was an important mechanism of DOX-induced cardiomyopathy and that Tau could partially improve the heart function by reducing calcium overload and alleviating downregulation of SERCA2a mRNA.