Effects of recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfection on inflammatory cytokine in isolated rat hearts with myocardial ischemia-reperfusion injury

Abstract

Objective To investigate the effects of recombinant adeno-associated virus (rAAV)-mediated heme oxygenase-1 (HO-1) gene transfer on inflammatory cytokine in isolated rat hearts with myocardial ischemia-reperfusion (I/R) injury. Methods Thirty male SD rats weighing 220-280 kg were randomly divided into 3 groups: group Ⅰ normal control (n=6); group Ⅱ normal saline + I/R (n=12) and group Ⅲ rAAV-HO-I +I/R (n=12). In group Ⅲ rAAV-mediated HO-1 was injected intramuscularly at 4 points on the anterior and posterior wall of left ventricle along the left anterior descending branch of coronary artery. In group Ⅱ normal saline was injected instead of rAAV- HO-1 gene. Six animals in each group were sacrificed 3 months after the gene delivery in group Ⅱ and Ⅲ The expression of HO-1 in the injected myocardium was determined by immuno-histnchemical technique. The isolated rat hearts were perfased with an oxygenated (95% O_2-5% CO_2) K-H solution at 37℃ in a Langendorff apparatus and subjected to 40 min of global ischemia followed by 45 min of reperfusion in group Ⅱ and Ⅲ. The left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) anti ±dp/dt_(max) were measured recorded at 15 min of post-preparation equilibration and at 15, 30 and 45 min of repcrfusion. TNF-α and IL-6 contents in myocardium were measured Results The HO-1 expression was significantly higher in group Ⅲ than in group Ⅱ (P < 0.05 or 0.01). The left ventricular function was significantly better and TNF-α and IL-6 contents in myocardium were significantly lower in group Ⅲ than in group Ⅱ (P <0.05 or 0.01). Conclusion rAAV-mediatcd HO-1 gene transfer can protect myocardium against I/R injury in isolated rat hearts through inhibition of inflammatory cytokine production. Key words: Heme oxygenase (decyclizing); Myocardial reperfusion injury; Transfection; Adenoviridae