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塞来昔布(一种选择性 COX-2 抑制剂)对大鼠肝缺血/再灌注诱导的氧化应激的影响。

The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats.

机构信息

Department of Pediatric Surgery, Dicle University Medical School, 21280 Diyarbakir, Turkey.

出版信息

Hepatol Res. 2006 Feb;34(2):76-83. doi: 10.1016/j.hepres.2005.11.003. Epub 2005 Dec 27.

Abstract

This study examined the effects of celecoxib on hepatic ischemia/reperfusion (I/R) injury in rats. A total of 40 male Sprague-Dawley rats weighing 190-210g were randomized into 4 groups of 10: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats that underwent liver ischemia for 1h followed by reperfusion for 45min; (4) I-R/Celecoxib group: rats pretreated with celecoxib (3mgkg(-1), i.p.) 40min before liver I/R. Tc-99m sulfur colloid images were used to measure the uptake ratio and perfusion index. Liver tissues were taken to determine SOD, CAT, GSH-Px, and MDA levels and for biochemical and histological evaluation. The plasma ALT, AST, GGT, and LDH activities were higher in group 3 than in group 4. The uptake ratio was significantly lower in group 3 compared to groups 1, 2, and 4. In addition, in group 4, the uptake ratio and perfusion index were also significantly higher compared to group 3. MDA values and the hepatic injury score decreased, while the SOD, CAT, and GSH-Px values increased in group 4 compared to group 3. In group 3, hepatocytes were swollen with marked vacuolization. Group 4 showed well preserved liver parenchyma with hepatocytes arranged radially around the central vein; there were regular sinusoidal structures with normal morphology without any signs of congestion. We showed that celecoxib has beneficial effects in hepatic I/R injury and may protect the liver.

摘要

这项研究旨在探讨塞来昔布对大鼠肝缺血/再灌注(I/R)损伤的影响。将 40 只雄性 Sprague-Dawley 大鼠(体重 190-210g)随机分为 4 组,每组 10 只:(1)对照组:未处理动物的数据;(2)假手术组:仅进行手术操作,但不进行肝 I/R,并给予生理盐水;(3)I/R 组:大鼠肝缺血 1h 后再灌注 45min;(4)I-R/Celecoxib 组:大鼠在肝 I/R 前 40min 预先给予塞来昔布(3mgkg(-1),腹腔注射)。采用 Tc-99m 硫胶体显像测定摄取率和灌注指数。取肝组织测定 SOD、CAT、GSH-Px 和 MDA 水平,并进行生化和组织学评估。与第 4 组相比,第 3 组大鼠血浆 ALT、AST、GGT 和 LDH 活性更高。与第 1、2 和 4 组相比,第 3 组的摄取率明显更低。此外,与第 3 组相比,第 4 组的摄取率和灌注指数也明显更高。与第 3 组相比,第 4 组 MDA 值和肝损伤评分降低,而 SOD、CAT 和 GSH-Px 值升高。第 3 组肝细胞肿胀,有空泡化明显。第 4 组肝组织保存良好,肝细胞呈放射状排列围绕中央静脉;有正常形态的规则窦状结构,无任何充血迹象。我们表明,塞来昔布对肝 I/R 损伤具有有益作用,可能对肝脏具有保护作用。

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