Abstract: Objective To study the new prevention and treatment method of hypertrophic myocardium by silencing the calcineurin Aβ（CaNAβ） gene. Methods Thirty adult Wistar rats were randomly divided into sham operation group,hypertrophic model group,RNAi group which was further divided into intra-pericardial intervention group,pericardial intervention group,and sublingual vein intervention group.The animals were killed with samples taken 6 days after transfection.Routine laboratory test was performed to detect hepatic and renal function and myocardial enzyme.Serum levels of CaNAβ,atrial natriuretic factor（ANF）,and β-myosin heavy chain（β-MHC） gene mRNA were measured by RT-PCR.Expression of CaNAβ in myocardial tissue was detected with immunofluorescence staining. Results The serum levels of CaNAβ,ANF,and β-MHC mRNA were higher in hypertrophic model group than in sham operation group（P＜0.05） and significantly lower in intramyocardial intervention group than in hypertrophic model group,pericardial intervention group and negative control group（P＜0.05）.Immunofluorescence staining of myocardiocytes was weaker in intrapericardial intervention group than in hypertrophic model group（P＜0.05）.No significant difference was found in plasma GPT/GOT,Ua/Cr/UN and CK/CK-MB/LDH levels among the 6 groups. Conclusion Intrapericardial injection of plasmid,use of microbubbles plus enzymes and ultrasound,can improve the transfection of plasmid in animal myocardial tissue.CaNAβgene intervention can inhibit expression of hypertrophy-related ANF and β-MHC genes with no significant damage to the heart,lung,liver and kidney tissues.