Peroxynitrite attenuates hepatic ischemia-reperfusion injury
Peroxynitrite attenuates hepatic ischemia-reperfusion injury
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DOI：
10.1152/ajpcell.2000.279.6.c1970
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发表时间：
2000-12-01
影响因子：
5.5
通讯作者：
Wong, PYK
中科院分区：
文献类型：
--
作者：
Liu, P;Xu, BH;Wong, PYK
在本研究中，我们研究了过氧亚硝基阴离子对再灌注损伤的影响，使用大鼠肝脏缺血再灌注（HI/R）模型。肝脏左叶和中叶缺血30分钟，然后再灌注4小时。A组和B组大鼠为假手术对照组，接受溶媒或过氧亚硝酸盐; C组和D组大鼠分别接受HI/R并接受过氧亚硝酸盐或溶媒。在再灌注后0、60和120分钟，通过门静脉导管以推注的方式给予2 μ mol/kg体重的过氧亚硝酸盐（稀释于盐水（pH 9.0，4 ℃）中）。结果显示，与D组相比，C组缺血肝叶超氧化物生成量和血浆谷丙转氨酶（ALT）活性分别降低了43%和45%。C组与D组相比，缺血肝叶和循环白细胞中的白细胞积聚分别减少40%和27%。C组缺血肝叶P-选择素和细胞间粘附分子-1（ICAM-1）mRNA与甘油醛-3-磷酸脱氢酶（GAPDH）mRNA的比值较D组降低。A组和B组在血浆ALT活性、循环白细胞、超氧化物生成和缺血肝叶中白细胞浸润方面无差异。此外，血液动力学参数（即，平均动脉血压、心脏指数、心搏指数和全身血管阻力）在组B、C和D之间没有显著差异。这些结果表明，通过门静脉给予过氧亚硝酸盐仅具有局部效应。生理浓度的外源性过氧亚硝酸盐减弱白细胞-内皮细胞相互作用，减少白细胞浸润。缺血肝叶白细胞浸润减少的机制可能与P-选择素和ICAM-1 mRNA表达减少有关。过氧亚硝酸盐给药的净效应可能是减少粘附分子介导的白细胞依赖性再灌注损伤。
In the present study, we examined the effects of peroxynitrite on reperfusion injury using a rat model of hepatic ischemia-reperfusion (HI/R). The left and median lobes of the liver were subjected to 30 min of ischemia, followed by 4 h of reperfusion. Groups A and B rats were sham-operated controls that received vehicle or peroxynitrite; groups C and D rats were subjected to HI/R and received peroxynitrite or vehicle, respectively. A dose of 2 mu mol/kg body wt of peroxynitrite, diluted in saline (pH 9.0, 4 degreesC), was administered as a bolus through a portal vein catheter at 0, 60, and 120 min after reperfusion. Results showed that superoxide generation in the ischemic lobes of the liver and plasma alanine aminotransferase (ALT) activity of group C were decreased by 43% and 45%, respectively, compared with group D. Leukocyte accumulations in the ischemic lobes of liver and circulating leukocytes were decreased by 40% and 27%, respectively, in group C vs. D. The ratios of mRNA of P-selectin and intercellular adhesion molecule-1 (ICAM-1) to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA extracted from the ischemic lobes of the liver of group C were decreased compared with group D. There were no differences between the groups A and B in terms of plasma ALT activity, circulating leukocytes, superoxide generation, and leukocyte infiltration in the ischemic lobes of the liver. Moreover, hemodynamic parameters (i.e., mean arterial blood pressure, cardiac index, stroke index, and systemic vascular resistance) were not significantly different among groups B, C, and D. These results suggest that administration of peroxynitrite via the portal vein only has a local effect. Exogenous peroxynitrite at physiological concentrations attenuates leukocyte-endothelial interaction and reduces leukocyte infiltration. The mechanism of the reduction of leukocyte infiltration into ischemic lobes of the liver appears because of decreased expression of mRNA of P-selectin and ICAM-1. The net effect of administration of peroxynitrite may be to reduce adhesion molecule-mediated, leukocyte-dependent reperfusion injury.