@phdthesis{oai:nagasaki-u.repo.nii.ac.jp:00004687,
 author = {畑地, 豪},
 month = {Sep},
 note = {Background: Ischemia-reperfusion (I/R) injury after lung transplantation causes alveolar damage, lung edema, and acute rejection. Poly(adenosine diphosphate-ribose) polymerase (PARP) is a single-stranded DNA repair enzyme that induces apoptosis and necrosis after DNA damage caused by reactive oxygen species. We evaluated tissue protective effects of the PARP inhibitor (PARP-i) PJ34 against pulmonary I/R injury.
Methods: Rats (total n=45) underwent a thoracotomy with left hilar isolation and saline administration (sham group) or thoracotomy with hilar clamping and saline administration (I/R group) or PJ34 administration (PARP-i group). Parameters were measured for 7 days after reperfusion.
Results: Pathologic analysis revealed that reperfusion injury was drastically suppressed in the PARP-i group 2 days after reperfusion. Terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling?positive cells were significantly decreased in the PARP-i group compared to the I/R group (P<0.05). Accordingly, the wet-to-dry lung ratio in the I/R group was significantly higher compared with the PARP-i group (P=0.025). Four hours after reperfusion, serum tissue necrosis factor-α and interleukin-6 were significantly suppressed in the PARP-i group compared with the I/R group (P<0.05). Serum derivatives of reactive oxygen metabolites increased quickly and remained high in the I/R and PARP-i groups from 4 hr until 7 days after reperfusion. Interestingly, the serum biologic antioxidant potential in the PARP-i group was significantly higher than that in the I/R group from day 2 until day 7.
Conclusion: The PARP-i decreased inflammation and tissue damage caused by pulmonary I/R injury. These beneficial effects of the PARP-i may be correlated with its antioxidative efficacy., 長崎大学学位論文 学位記番号:博(医歯薬)甲第704号 学位授与年月日:平成26年9月3日, Author: Go Hatachi, Tomoshi Tsuchiya, Takuro Miyazaki, Keitaro Matsumoto, Naoya Yamasaki, Naoyuki Okita, Atsushi Nanashima, Yoshikazu Higami, Takeshi Nagayasu, Citation: Transplantation, 98(6), pp.618-624; 2014, Nagasaki University (長崎大学), 博士(医学) (2014-09-03)},
 school = {Nagasaki University (長崎大学)},
 title = {The Poly(Adenosine Diphosphate-Ribose) Polymerase Inhibitor PJ34 Reduces Pulmonary Ischemia-Reperfusion Injury in Rats},
 year = {2014}
}