慢性心力衰竭犬心肌过表达肌浆网Ca^(2+)-ATP酶的安全性分析

Safety of Sarcoplasmic Reticulum Ca^(2+)-ATPase Gene Transfer by Intramyocardium Administration in Chronic Heart Failure Beagles

目的研究心肌注射法转导肌浆网Ca2+-ATP酶(SERCA2a)基因治疗慢性心力衰竭犬的安全性。方法检测SER-CA2a基因转导心力衰竭犬的心肌酶学、心肌组织内cAMP含量、心肌耗氧量、心律失常及系统炎症指标、肝肾功能。结果 SER-CA2a基因转导治疗不增加细胞内cAMP浓度,心律失常的发生率和心肌氧耗未增加,未引起明显的全身炎症反应和肝肾功能的损伤。结论 SERCA2a基因转导是一种安全的治疗策略。

Objective To assess the safety of intramyocardium injection of sarcoplasmic reticulum Ca2＋-ATPase（SERCA2a）to rescue chronic heart failure beagles.MethodsThe heart failure beagles were assessed with myocardium enzymology,cAMP content of myocardium,myocardial oxygen consumption,arrhythmia,systemic inflammation factors,and the function of liver and kidney after SERCA2a gene transferred.ResultsThere were no increase of cAMP content,no more arrhythmia,myocardial oxygen consumption,no apparente systemic inflammation,and no injures to hepatic and renal function.ConclusionOverexpression of SERCA2a by intramyocardium injection is relatively safe.