Huang Jianhua, Ito Yoshinori, Morikawa Masayuki, Uchida Hiroaki, Kobune Masayoshi, Sasaki Katsunori, Abe Tomio, Hamada Hirofumi
Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan.
Biochem Biophys Res Commun. 2003 Nov 7;311(1):64-70. doi: 10.1016/j.bbrc.2003.09.160.
Ischemia and reperfusion (I/R) injury causes the progression of cardiac dysfunction. The prevention of cardiomyocyte-loss due to I/R injury is important for the treatment of heart failure. Therefore, we employed antiapoptotic Bcl-xL protein to prevent I/R injury in the heart and evaluated the cardioprotective effect of Bcl-xL transduction by adenoviral vector (Adv) after I/R injury. Adv with Bcl-xL gene was injected in the rat heart 4 days prior to I/R. The prevention of cardiac performance-loss and the reduction of cardiac apoptosis, after 30min ischemia and 30min reperfusion of global I/R, were demonstrated in the heart with adenoviral Bcl-xL transduction. Also, significant reductions of the infarct size and serum creatine kinase levels were observed in the heart transduced with Bcl-xL gene compared with control after 30min ischemia and 24h reperfusion of the left anterior coronary artery. Thus, Bcl-xL may serve as a potential therapeutic tool for cardioprotection.
缺血再灌注(I/R)损伤会导致心脏功能障碍的进展。预防因I/R损伤导致的心肌细胞丢失对于心力衰竭的治疗至关重要。因此,我们采用抗凋亡的Bcl-xL蛋白来预防心脏的I/R损伤,并评估腺病毒载体(Adv)介导的Bcl-xL转导在I/R损伤后对心脏的保护作用。在I/R前4天,将携带Bcl-xL基因的Adv注入大鼠心脏。在进行30分钟全心缺血和30分钟再灌注后,腺病毒介导的Bcl-xL转导的心脏表现出心脏功能丧失的预防以及心脏细胞凋亡的减少。此外,在左冠状动脉前降支进行30分钟缺血和24小时再灌注后,与对照组相比,转导Bcl-xL基因的心脏梗死面积和血清肌酸激酶水平显著降低。因此,Bcl-xL可能作为一种潜在的心脏保护治疗工具。