The value of intrapericardial injection with a trans-diaphrag matic approach in the gene therapy of chronic heart failure rats / 中国病理生理杂志

ABSTRACT

AIM: To study the feasibility, security a nd validity of the intrapericardial injection with a trans-diaphragmatic approach in chronic heart failure rats and its value in the study of gene therapy for hea rt diseases, and further investigate whether adeno-associated virual gene transf er of sarcoplasmic reticulum Ca 2+-ATPase (SERCA2a) gene can improve ven tricular function in chronic heart failure (HF) rats. METHODS: An animal model of heart failure was obtained by creati ng descending aortic constriction in rats. Recombinant adeno-associated virus, c arrying enhanced green fluorescent protein (EGFP) gene and recombinant adeno-ass ociated virus carrying SERCA2a gene, were respectively injected into pericardium of heart failure rats in different groups (group HF+EGFP and group HF+SERCA2a) by intrapericardial injection with a trans-diaphragmatic approach. After 30 days , hemodynamic parameters were measured and analyzed. Cryosection was analyzed by fluorescence microscopy to examine the expression of green fluorescent protein, and Western blotting was performed to detect the expression of SERCA2a. RESULTS: Green fluorescence was detected in cryosection of the h earts in all rats in group HF+EGFP and the expression of green fluorescent prote in was ubiquitously. The expression of SERCA2a in all rats in group HF+SERCA2a w as more than those in group HF and group HF+EGFP. And overexpression of SERCA2a improved the systolic and diastolic function of heart failure rats significantly and the hemodynamic parameters were similar with those of the controls. CONCLUSION: The intrapericardial injection with a trans-diaphrag matic approach suggests a simple, safe, efficient and cheap technique for the ge ne therapy of chronic heart failure. Gene thransfer of SERCA2a may be a new appr oach for the treatment of chronic heart failure.