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过氧亚硝酸盐分解催化剂FeTMPyP对幼鼠肠道缺血再灌注损伤具有部分保护作用。

Peroxynitrite decomposition catalyst FeTMPyP provides partial protection against intestinal ischemia and reperfusion injury in infant rats.

作者信息

Stefanutti Giorgio, Pierro Agostino, Smith Virpi V, Klein Nigel J, Eaton Simon

机构信息

Units of Paediatric Surgery, Institute of Child Health, London, WC1N 1EH, United Kingdom.

出版信息

Pediatr Res. 2007 Jul;62(1):43-8. doi: 10.1203/PDR.0b013e31806790c0.

DOI:10.1203/PDR.0b013e31806790c0
PMID:17515836
Abstract

Free radicals are important in development of intestinal ischemia-reperfusion (I/R) injury, leading to intestinal and pulmonary damage. We evaluated the effects of peroxynitrite decomposition catalyst FeTMPyP in infant intestinal I/R. Suckling rats underwent 40 min intestinal ischemia + 90 min reperfusion. At reperfusion, animals received saline or FeTMPyP. Groups were (n = 11 per group): 1) control+saline; 2) I/R+saline; 3) I/R+FeTMPyP. Increased histologic injury and ICAM-1 expression were observed in ileum of both I/R+saline and I/R+FeTMPyP rats, but P-selectin expression was increased in I/R+saline animals only versus controls. Myeloperoxidase (neutrophil infiltration marker) was increased in ileum and lungs of I/R+saline rats, but FeTMPyP prevented this in the ileum. I/R+saline animals showed higher malondialdehyde (lipid peroxidation marker) in ileum and lungs versus both control+saline and I/R+FeTMPyP rats. Glutathione was decreased in all I/R animals, but oxidized and total glutathione were higher in I/R+FeTMPyP than the I/R+saline group. Nitrate+nitrite concentration (systemic nitric oxide production) was elevated in I/R+saline but not in I/R+FeTMPyP animals. FeTMPyP provides limited protection against intestinal I/R in neonatal rats by reducing ileal P-selectin expression, systemic nitric oxide production, neutrophil infiltration in ileum and lipid peroxidation in both lungs and ileum; and preserving intestinal antioxidant capacity.

摘要

自由基在肠道缺血再灌注(I/R)损伤的发展过程中起着重要作用,会导致肠道和肺部损伤。我们评估了过氧亚硝酸盐分解催化剂FeTMPyP对幼鼠肠道I/R的影响。乳鼠经历40分钟的肠道缺血 + 90分钟的再灌注。在再灌注时,动物接受生理盐水或FeTMPyP。分组如下(每组n = 11):1)对照组 + 生理盐水;2)I/R + 生理盐水;3)I/R + FeTMPyP。在I/R + 生理盐水组和I/R + FeTMPyP组的大鼠回肠中均观察到组织学损伤增加和ICAM - 1表达增加,但与对照组相比,仅I/R + 生理盐水组动物的P - 选择素表达增加。髓过氧化物酶(中性粒细胞浸润标志物)在I/R + 生理盐水组大鼠的回肠和肺中增加,但FeTMPyP可预防回肠中的这种情况。与对照组 + 生理盐水组和I/R + FeTMPyP组大鼠相比,I/R + 生理盐水组动物的回肠和肺中的丙二醛(脂质过氧化标志物)更高。所有I/R组动物的谷胱甘肽均减少,但I/R + FeTMPyP组的氧化型和总谷胱甘肽高于I/R + 生理盐水组。I/R + 生理盐水组的硝酸盐 + 亚硝酸盐浓度(全身一氧化氮产生)升高,但I/R + FeTMPyP组动物未升高。FeTMPyP通过降低回肠P - 选择素表达、全身一氧化氮产生、回肠中性粒细胞浸润以及肺和回肠中的脂质过氧化;并保留肠道抗氧化能力,为新生大鼠的肠道I/R提供有限的保护。

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