Mechanism of the production of reactive nitrogen species during renal ischemic-reperfusion insult

肾缺血再灌注损伤过程中活性氮的产生机制

• 批准号: 13670087
• 负责人: TAMAKI Toshiaki
• 金额: $ 2.24万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670087/
• 关键词: Nitric oxide; HbNO; electron paramagnetic resonance; ACE inhibitor; subtraction method; ischemia-reperfused kidney; ^<15>NO_2; Nitrite; Nitrotyrosine; Electron paramagnetic reson; L-tyrosine; Tyrosine radical; Peroxynitrite

In circulation, nitric oxide(NO) exists as relatively atable hemoglobin-NO adduct(HbNO), which means that the amount of HbNO may reflect the blood NO concentration. HbNO signal has been reported to be successfully detected in human blood using electron paramagnetic resonance(EPR) method. However, there were some difficulties to obtain a fine HbNO signal of nornal blood. We itroduced the EPR signal subtraction method to overcome the difficulties. Using this method, we confirmed that HbNO concentrarion in pentobarbital-anesthetized rats were augmented by infusion of L-arginine but not D-argimine. We also emenstrated that temocapril, an ACE inhibitor, improved abnormalities of NO dynamics in the L-MAME-induced hypertensive rats.After the intravebous infusion of ^<15>NO_2, the left renal artery of a rat was clumped for 40 minutes. Five minutes after the release of left renal occluaion, left and right renal tissues and venous blood were obtained. Hb^<15>NO concentration of renal tissues and venous blood was evaluated using EPR method. Hb^<15>NO concentrarion of left (ischemic) renal tissue is much higher than that of right(non-ischemic) renal tissue. Hb^<15>NO concentration of venous blood in ischemic-reperfused rat is much higher than that in aham operated non-ischemic rat. These results indicate that there is NO generation pathway from NO_2 and ischemic-reperfusion insult stimulates the NO generation from NO_2

在循环中，一氧化氮（NO）以相对稳定的血红蛋白-NO加合物（HbNO）的形式存在，这意味着HbNO的量可以反映血液中NO的浓度。据报道，使用电子顺磁共振（EPR）方法可以成功检测人体血液中的 HbNO 信号。然而，获得正常血液的精细HbNO信号存在一些困难。我们引入了EPR信号减法来克服这个困难。使用这种方法，我们证实了戊巴比妥麻醉大鼠的 HbNO 浓度因输注 L-精氨酸而不是 D-精氨酸而增加。我们还证明ACE抑制剂temocapril改善了L-MAME诱导的高血压大鼠的NO动态异常。静脉输注^ 15 NO_2后，大鼠的左肾动脉凝结40分钟。左肾闭塞解除5分钟后，取左右肾组织及静脉血。使用EPR方法评估肾组织和静脉血的Hb^ 15 NO浓度。左(缺血)肾组织的Hb 15 NO浓度远高于右(非缺血)肾组织。缺血再灌注大鼠的静脉血Hb 15 NO浓度远高于aham手术的非缺血大鼠。这些结果表明存在NO_2生成NO的途径，并且缺血再灌注损伤刺激NO_2生成NO

项目成果

K.Tsuchiya: "The role of thiol and nitrosothiol compounds in the nitric oxide-forming reactions of the iron-N-methyl-D-glucamine dithiocarbamate complex"Biochemical Journal. 367. 771-779 (2002)

K.Tsuchiya：“硫醇和亚硝基硫醇化合物在铁-N-甲基-D-葡萄糖胺二硫代氨基甲酸盐复合物的一氧化氮形成反应中的作用”生物化学杂志。

土屋浩一郎: "亜硝酸と一酸化窒素(NO)"血管. 25. 63-71 (2002)

土屋晃一郎：“亚硝酸盐和一氧化氮 (NO)”血管。25. 63-71 (2002)

S.Kagami: "Requirement for tyrosine kinase-ERK1/2 signaling in α1β1 integrin-mediated collagen matrix remodeling by rat mesangial cells"Experimental Cell Research. 268. 274-283 (2001)

S. Kagami：“大鼠系膜细胞 α1β1 整合素介导的胶原基质重塑中酪氨酸激酶-ERK1/2 信号传导的要求”实验细胞研究 268. 274-283 (2001)。

M.Yoshizumi, T.Kogane, Y.Suzaki, K.Kirima, Moe Kyaw, K.Kirima, K.Ishizawa, K.Tsuchiya, S.Kagami, T.Tamaki: "Ebeelen attenuates oxidative styress-induced apoptosis via the inhibition of the c jun N-terminal kinase and activator protein-1 signaling pathway

M.Yoshizumi、T.Kogane、Y.Suzaki、K.Kirima、Moe Kyaw、K.Kirima、K.Ishizawa、K.Tsuchiya、S.Kagami、T.Tamaki：“Ebeelen 通过抑制来减弱氧化苯乙烯诱导的细胞凋亡

K.Tsuchiya, K.Kirima, M.Yoshizumi, H.Houchi, T.Tamaki, RP.Mason: "The role of thiol and nitrosothiol compounds in the nitric oxide-forming reactions of the iron-N-methyl-D-glucamine dithiocarbamate complex"Biochemical Journal. 367. 771-779 (2002)

K.Tsuchiya、K.Kirima、M.Yoshizumi、H.Houchi、T.Tamaki、RP.Mason：“硫醇和亚硝基硫醇化合物在铁-N-甲基-D-葡萄糖胺的一氧化氮形成反应中的作用