Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion
Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion
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DOI：
10.1096/fasebj.14.9.1061
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发表时间：
2000-06-01
期刊：
影响因子：
4.8
通讯作者：
Salvemini, D
中科院分区：
文献类型：
--
作者：
Cuzzocrea, S;Misko, TP;Salvemini, D
本研究旨在探讨过亚硝酸根分解催化剂5，10，15，20-tetrakis(2，4，6-trimethyl-3，5-disulfonatophenyl)-porphyrinato铁(Ⅲ)对内脏动脉闭塞性休克(SAO)模型的保护作用。夹闭大鼠肠系膜上动脉和腹主动脉45min，然后松开夹闭(再灌流)，造成SAO休克模型。再灌流60min后处死动物进行组织学和生化检查。SAO休克大鼠血浆中二氢罗丹明123氧化为罗丹明(过氧亚硝酸盐诱导的氧化过程的标志物)在再灌流后显著增加，但不是单独在缺血时。免疫组织化学检查显示，休克大鼠坏死性回肠对硝基酪氨酸的免疫反应性显著增加。SAG休克大鼠组织髓过氧化物酶和丙二醛活性显著升高，回肠远端组织学损伤明显。SAO休克也与显著的死亡率相关(再灌流后2小时存活率为0)。SAG休克大鼠回肠组织切片P-选择素染色阳性，主要定位于血管内皮细胞。SAO休克大鼠回肠组织切片，ICAM-1抗体染色呈弥漫性染色。给予FeTMPS可明显减轻肠缺血再灌注损伤，降低再灌注期脂质和过氧化亚硝酸盐的生成。PN催化剂处理也显著降低SAG休克大鼠组织切片中P-选择素和ICAM-1的染色强度和程度，并提高存活率。我们的结果清楚地表明，过氧亚硝酸盐分解催化剂在SAO中起到保护作用，这种作用可能是由于抑制了黏附分子的表达和与过氧亚硝酸盐相关的途径相关的组织损伤。-Cuzzocrea S.，Misko，TP.，Costantino，C.，Mazzon，E.，Micali，A.，Caputi，A.，Macarthur，H.，Salemini，D.过氧亚硝酸盐分解催化剂在内脏动脉闭塞和再灌注大鼠模型中的有益作用。
The aim of the present study was to investigate the protective effect of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-disulfonatophenyl)-porphyrinato iron (III) (FeTMPS) in a model of splanchnic artery occlusion shock (SAO). SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by release of the clamp (reperfusion). At 60 min after reperfusion, animals were killed for histological examination and biochemical studies. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine (a marker of peroxynitrite-induced oxidative processes) in the plasma of the SAO-shocked rats after reperfusion, but not during ischemia alone. Immunohistochemica1 examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, an index of nitrogen species such as peroxynitrite, in the necrotic ileum in shocked rats. SAG-shocked rats developed a significant increase of tissue myeloperoxidase and malonaldehyde activity, and marked histological injury to the distal ileum. SAO shock was also associated with a significant mortality (0% survival at 2 h after reperfusion). Reperfused ileum tissue sections from SAG-shocked rats showed positive staining for P-selectin localized mainly in the vascular endothelial cells. Ileum tissue sections obtained from SAO-shocked rats and stained with antibody to ICAM-1 showed a diffuse staining. Administration of FeTMPS significantly reduced ischemia/reperfusion injury in the bowel, and reduced lipid and the production of peroxynitrite during reperfusion. Treatment with PN catalyst also markedly reduced the intensity and degree of P-selectin and ICAM-1 staining in tissue sections from SAG-shocked rats and improved survival. Our results clearly demonstrate that peroxynitrite decomposition catalysts exert a protective effect in SAO and that this effect may be due to inhibition of the expression of adhesion molecules and the tissue damage associated with peroxynitrite-related pathways.-Cuzzocrea S., Misko, T. P., Costantino, C., Mazzon, E., Micali, A., Caputi, A. P., Macarthur, H., Salvemini, D. Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion.