Role of poly(ADP-ribose) polymerase activation in development of multiple organ failure in ischemia-reperfusion injury
聚(ADP-核糖)聚合酶激活在缺血再灌注损伤中多器官衰竭发展中的作用
基本信息
- 批准号:14571165
- 负责人:
- 金额:$ 2.05万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2002
- 资助国家:日本
- 起止时间:2002 至 2003
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Purpose : We evaluated the cytoprotective effects of 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) polymerase (PARP), in multiple organ failure in ischemia-reperfusion injury.Methods : Rats, administered either 3AB (3AB group) or saline (control group), were subjected to intestinal ischemia (90 minutes) and reperfusion. Sham group rats underwent simple laparotomy. 3AB improved the survival rate and tissue blood flow after intestinal ischemia-reperfusion.Results : Compared with sham group rats, intestinal and hepatic ATP levels in the control group and 3AB group were decreased after intestinal ischemia-reperfusion. The 3AB group, however, had significantly higher intracellular ATP levels in the intestine as well as liver than the control group. Moreover, histological evaluation revealed that the 3AB group had less intestinal mucosal damage than the control group. Control rats showed positive staining of the residual basal intestinal mucosa by immunohistological staining of TUNEL, 8-hydroxyguanosine, PARP and PARP-85kD segment, while 3AB-treated rats did not. In the liver, both the control group and 3AB group had a higher ratio of PARP-positive stained cells compared with the sham group. The control group, however, had a higher ratio of PARP-85kD segment-staining cells, a very sensitive indicator of apoptosis, than the 3AB and sham groups.Conclusion : We concluded that inhibition of poly(ADP-ribose) polymerase activation could ameliorate multiple organ failure by preserving intracellular ATP levels in ischemia-reperfusion injury.
目的:研究聚adp核糖聚合酶(PARP)抑制剂3-氨基苯甲酰胺(3AB)在缺血再灌注损伤多器官功能衰竭中的细胞保护作用。方法:大鼠分别给予3AB (3AB组)和生理盐水(对照组)进行肠缺血(90分钟)和再灌注。假手术组大鼠行单纯剖腹手术。3AB可提高肠缺血再灌注后的存活率和组织血流量。结果:与假手术组大鼠比较,对照组和3AB组大鼠肠缺血再灌注后肠道和肝脏ATP水平均降低。然而,3AB组在肠道和肝脏的细胞内ATP水平明显高于对照组。组织学评价显示,3AB组肠黏膜损伤程度小于对照组。TUNEL、8-羟基鸟苷、PARP和PARP- 85kd段免疫组织染色显示对照组大鼠残留基础肠黏膜阳性,而3ab处理大鼠未见阳性。在肝脏中,对照组和3AB组的parp阳性染色细胞比例均高于假手术组。然而,与3AB和sham组相比,对照组的PARP-85kD片段染色细胞比例更高,这是一种非常敏感的细胞凋亡指标。结论:抑制多聚腺苷核糖聚合酶激活可通过维持缺血再灌注损伤时细胞内ATP水平来改善多器官功能衰竭。
项目成果
期刊论文数量(30)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Shimizu T, Yonekura T et al.: "Late onset of right Bochdalek's hernia with strangulation of the omentum"Acta Paediatr. 91. 483-485 (2002)
Shimizu T、Yonekura T 等人:“伴有大网膜绞窄的右侧 Bochdalek 疝迟发”Acta Paediatr。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
肝部分虚血再還流障害のDNA障害とATP枯渇に対する3-aminobenzamideの抑制効果に関する実験的検討
3-氨基苯甲酰胺抑制部分肝缺血再灌注损伤引起的DNA损伤和ATP耗竭的实验研究
- DOI:
- 发表时间:2002
- 期刊:
- 影响因子:0
- 作者:山内勝治;米倉竹夫;など
- 通讯作者:など
虚血再灌流におけるpoly(ADP-ribose)polymeraseの活性化と多臓器不全発生のメカニズムの検討
缺血再灌注过程中聚(ADP-核糖)聚合酶的激活及多器官功能衰竭的机制研究
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:野上隆司;米倉竹夫;など
- 通讯作者:など
Yamauchi K, Yonekura et al.: "Benign transient non-organic ileus of neonates"Eur J Pediatr Surg. 12. 168-174 (2002)
Yamauchi K、Yonekura 等人:“新生儿良性短暂性非器质性肠梗阻”Eur J Pediatr Surg。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
3-aminobenzamide inhibits DNA damage and consumption of intracellular ATP in hepatic ischemia reperfusion.
3-aminobenzamide 抑制肝缺血再灌注过程中的 DNA 损伤和细胞内 ATP 的消耗。
- DOI:
- 发表时间:2002
- 期刊:
- 影响因子:0
- 作者:Yamauchi K;Yonekura T;et al.
- 通讯作者:et al.
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YONEKURA Takeo其他文献
YONEKURA Takeo的其他文献
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{{ truncateString('YONEKURA Takeo', 18)}}的其他基金
Interaction of nitric oxide and reactive oxygen on ADP-ribose-polymerase activation DNA damage
一氧化氮和活性氧相互作用对 ADP-核糖聚合酶激活 DNA 损伤的影响
- 批准号:
12671186 - 财政年份:2000
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mechanism of multiple organ failure caused by interaction of nitric oxide and oxidant stress
一氧化氮与氧化应激相互作用引起多器官衰竭的机制
- 批准号:
10671142 - 财政年份:1998
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Nitric oxide and superoxide in ishcemia/reperfusion injury
一氧化氮和超氧化物在缺血/再灌注损伤中的作用
- 批准号:
08671400 - 财政年份:1996
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)