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氧自由基在大鼠转流性结肠炎发病机制中的重要性。

The importance of oxygen free radicals in the etiopathogenesis of diversion colitis in rats.

作者信息

Martinez Carlos Augusto Real, Ribeiro Marcelo Lima, Gambero Alessandra, Miranda Daniel Duarte da Conceição, Pereira José Aires, Nadal Sidney Roberto

机构信息

Santa Casa Faculty of Medical Sciences, USF, Sao Paulo, Brazil.

出版信息

Acta Cir Bras. 2010 Oct;25(5):387-95. doi: 10.1590/s0102-86502010000500002.

Abstract

PURPOSE

Quantify the levels of oxidative DNA damage of epithelial colon cells comparing segments with and without fecal stream.

METHODS

Sixty Wistar rats were subjected to deviation of fecal stream by proximal colostomy and a distal mucosal fistula. Animals were divided into three experimental groups that were sacrificed 6, 12 and 24 weeks after surgery. In each experimental group, five animals underwent laparotomy without intestinal deviation (sham subgroup). The diagnosis of colitis was made by histopathological analysis and the inflammatory activity index by graduated scale. The neutrophil infiltration was determined by myeloperoxidase tissue levels and the intensity of oxidative DNA damage by comet assay. The Mann-Withney and Student t test were used to compare the results among experimental subgroups and the Kruskal-Wallis test for variance analysis, adopting a significance level of 5% (p<0.05).

RESULTS

Colon segments without fecal stream was shown higher histological inflammatory score of the colon wall after 12 and 24 weeks (p=0.001) that increased with the time of diversion (p=0.01). The activity of myeloperoxidase in segments without fecal stream decreased with the time (p=0.001). Oxidative DNA damage levels were significantly higher in the segments without fecal stream, (p=0.0001), independent of time of colon diversion, and increase with the time (p=0.0007).

CONCLUSIONS

Colon segments without fecal stream showed high levels of oxidative DNA damage related to histological alterations observed in diversion colitis. The levels of oxidative DNA damage in segments devoid of the fecal stream increase with the time of intestinal exclusion.

摘要

目的

比较有和没有粪便流的结肠段上皮细胞中氧化性DNA损伤的水平。

方法

60只Wistar大鼠通过近端结肠造口术和远端黏膜瘘使粪便流改道。动物被分为三个实验组,在手术后6、12和24周处死。在每个实验组中,五只动物接受了无肠道改道的剖腹手术(假手术亚组)。通过组织病理学分析诊断结肠炎,并通过分级量表评估炎症活动指数。通过髓过氧化物酶组织水平测定中性粒细胞浸润,通过彗星试验测定氧化性DNA损伤的强度。采用Mann-Withney检验和Student t检验比较各实验亚组的结果,采用Kruskal-Wallis检验进行方差分析,显著性水平为5%(p<0.05)。

结果

无粪便流的结肠段在12周和24周后显示出结肠壁更高的组织学炎症评分(p=0.001),且随着改道时间增加(p=0.01)。无粪便流的结肠段中髓过氧化物酶的活性随时间降低(p=0.001)。无粪便流的结肠段中氧化性DNA损伤水平显著更高(p=0.0001),与结肠改道时间无关,并随时间增加(p=0.0007)。

结论

无粪便流的结肠段显示出与改道性结肠炎中观察到的组织学改变相关的高水平氧化性DNA损伤。无粪便流的结肠段中氧化性DNA损伤水平随肠道排除时间增加。

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