Role of poly( ADP-ribose) polymerase-1 on lung ischemia-reperfusion injury in rats: the relation-ship with autophagy / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of poly( ADP-ribose) polymerase-1 ( PARP-1) in lung ischemia-reperfusion ( I/R ) injury in rats and the relationship with autophagy. Methods Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-240 g, were divided into 3 groups (n=8 each) using a random number table method: sham operation group (S group), lung I/R group ( I/R group) and lung I/R plus PARP-1 inhibitor PJ34 group ( I/R+PJ34 group) . The chest was only opened without clamping the left hilum of lung in group S. Lung I/R injury model was established by clam-ping the left hilum of lung for 45 min followed by 120 min reperfusion in I/R and I/R+PJ34 groups. PJ3410 mg/kg was intraperitoneally injected at 30 min before ischemia in group I/R+PJ34, while the equal volume of normal saline was injected in S and I/R groups. The rats were sacrificed at the end of reperfusion, and lungs were removed for microscopic examination of the pathological changes ( with a light microscope) which were scored and for determination of wet to dry weight ratio ( W/D ratio) , cell apoptosis ( by TUNEL) , ex-pression of PARP-1 activity markers ( PAR) , Bcl-2, Bax, microtubule-associated protein 1 light chain 3Ⅰ ( LC3-Ⅰ) , LC3-Ⅱ and Beclin-1 ( using Western blot ) . The apoptosis index, Bcl-2/Bax ratio and LC3-Ⅱ/LC3-Ⅰ ratio were calculated. Results Compared with S group, the W/D ratio, pathological scores, apoptosis index and LC3-Ⅱ/LC3-Ⅰ ratio were significantly increased, the expression of PAR and Beclin-1 was up-regulated, and Bcl-2/Bax ratio was decreased in I/R and I/R+PJ34 groups (P＜0. 05). Compared with I/R group, the W/D ratio, pathological scores, apoptosis index, and LC3-Ⅱ/LC3-Ⅰratio were significantly decreased, the expression of PAR and Beclin-1 was down-regulated, and Bcl-2/Bax ratio was increased in I/R+PJ34 group ( P＜0. 05) . Conclusion PARP-1 activation is involved in lung I/R inju-ry in rats, and the mechanism may be related to increasing autophagy and inducing cell apoptosis.