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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

基本信息

批准号：
12671186
负责人：
YONEKURA Takeo
金额：
$ 2.18万
依托单位：
KINKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

Purpose : To reveal the mechanism of ischemia reperfusion injury, we evaluate intracellular ATP levels and DNA damage and organ damage in ischemia reperfusion with inhibition of poly(ADP-ribose) polymerase activation and NO production. Methods : 60 min. ischemia and 180 min. reperfusion in the 70% liver of the male Wister rats were performed. The 3AB group rats received PARS inhibitor, 3-aminobenzamide, and the L-NAME group rats received NO inhibitor, L-NAME, before ischemia. The control group rats were infused saline. The sham group rats were treated only dissection of portal area without ischemia reperfusion. Tissue damage and DNA damage was evaluated both in the ischemia reperfused liver (IR-liver) and the non-ischemia reperfused liver (NIR-liver). Nitrotyrosine stain was performed for evaluating tissue damage by ONOO-. Serum ALP levels, intrahepatic ATP levels and Nitrotyrosine levels were also evaluated in each group. Results : The L-NAME group had highest serum ALT levels compare … More d with the control and the 3AB groups. The control and the L- NAME groups had severe tissue and DNA damages in the IR-liver, while the 3AB group had mild tissue and DNA damages in the IR-liver. There were not differences in the NIR-liver among 4 groups. The IR-love in the control and the 3AB groups had high nitrotyrosine staining. They also had high tissue concentrations of nitrotyrosine. The L-NAME group did not have any nitrotyrosine staining or production. In the IR-liver, the 3AB group had higher intrahepatic ATP levels than the control and the L-NAME groups. In the NIR-liver, although the control and the L-NAME groups had lower levels of intrahepatic ATP levels compared with the sham group, the 3AB group had same intrahepatic ATP levels as the sham group. Conclusion : We concluded that multiple organ failure developed in the ischemia reperfusion injury would be due to consumption of intracellular ATP with activation of PARS to repair DNA damage caused by free radicals in ischemia reperfusion. Less

目的：为了揭示缺血再灌注损伤的机制，我们通过抑制聚（ADP-核糖）聚合酶的活化和NO的产生来评价缺血再灌注时细胞内ATP水平和DNA损伤以及器官损伤。方法：雄性Wister大鼠70%肝脏缺血60 min，再灌注180 min。3AB组在缺血前给予PARS抑制剂3-氨基苯甲酰胺，L-NAME组在缺血前给予NO抑制剂L-NAME。对照组输注生理盐水。假手术组大鼠仅行门脉区切除，不进行缺血再灌注。在缺血再灌注肝（IR-肝）和非缺血再灌注肝（NIR-肝）中评价组织损伤和DNA损伤。硝基酪氨酸染色评价ONOO-对组织的损伤。还评价了各组的血清ALP水平、肝内ATP水平和硝基酪氨酸水平。结果：L-NAME组血清ALT水平最高， ...更多信息 d与对照组和3AB组比较。对照组和L-NAME组IR肝组织和DNA损伤严重，而3AB组IR肝组织和DNA损伤轻微。4组间肝脏NIR无差异。对照组和3AB组的IR-love具有高的硝基酪氨酸染色。他们也有高浓度的硝基酪氨酸组织。L-NAME组没有任何硝基酪氨酸染色或产生。在IR-肝脏中，3AB组的肝内ATP水平高于对照组和L-NAME组。在NIR-肝脏中，尽管对照组和L-NAME组的肝内ATP水平低于假手术组，但3AB组的肝内ATP水平与假手术组相同。结论：我们认为，在缺血再灌注损伤中发生的多器官功能衰竭可能是由于细胞内ATP的消耗和PARS的激活，以修复缺血再灌注中自由基引起的DNA损伤。少