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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.\nMethods: 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.\nResults: 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\u003c0.05). 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The Poly(Adenosine Diphosphate-Ribose) Polymerase Inhibitor PJ34 Reduces Pulmonary Ischemia-Reperfusion Injury in Rats
http://hdl.handle.net/10069/35827
http://hdl.handle.net/10069/3582742d88aca-eb56-4f44-a1ca-351bfb78920b
名前 / ファイル | ライセンス | アクション |
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ISYK704_Hatachi.pdf (8.8 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2015-09-08 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | The Poly(Adenosine Diphosphate-Ribose) Polymerase Inhibitor PJ34 Reduces Pulmonary Ischemia-Reperfusion Injury in Rats | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Ischemia-reperfusion injury | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | PARP inhibitor | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | PJ34 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Antioxidants | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
畑地, 豪
× 畑地, 豪 |
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著者別名 | ||||||
姓名 | Hatachi, Go | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 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 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Author: Go Hatachi, Tomoshi Tsuchiya, Takuro Miyazaki, Keitaro Matsumoto, Naoya Yamasaki, Naoyuki Okita, Atsushi Nanashima, Yoshikazu Higami, Takeshi Nagayasu | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Citation: Transplantation, 98(6), pp.618-624; 2014 | |||||
書誌情報 |
Transplantation 巻 98, 号 6, p. 618-624, 発行日 2014-09-03 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 00411337 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1097/TP.0000000000000305 | |||||
権利 | ||||||
権利情報 | c 2014 Lippincott Williams & Wilkins. | |||||
権利 | ||||||
権利情報 | This article is publised under the terms of the Creative Commons License Attribution-NonCommerical No Derivative 3.0 which allows readers to disseminate and reuse the article, as well as share and reuse the scientific material. It does not permit commercial exploitation or the creation of derivative works without specific permission. To view a copy of this license visit http://creativecommons.org/licenses/by-nc-nd/3.0. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
その他のタイトル | ||||||
その他のタイトル | ポリADPリボースポリメレース阻害薬(PJ34)はラットにおける肺虚血再灌流障害を軽減する | |||||
出版者 | ||||||
出版者 | Lippincott Williams & Wilkins | |||||
関係URI | ||||||
識別子タイプ | HDL | |||||
関連識別子 | http://hdl.handle.net/10069/34876 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 17301 | |||||
学位授与機関名 | Nagasaki University (長崎大学) | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2014-09-03 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲医歯薬第704号 | |||||
学位の種類 | ||||||
課程博士 | ||||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Nagasaki University (長崎大学), 博士(医学) (2014-09-03) |