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帕瑞昔布预处理可减轻大鼠肝脏缺血/再灌注损伤。

Pretreatment of parecoxib attenuates hepatic ischemia/reperfusion injury in rats.

作者信息

Zhang Tao, Ma Yi, Xu Kang-Qing, Huang Wen-Qi

机构信息

Department of Anesthesiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Organ transplantation center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

出版信息

BMC Anesthesiol. 2015 Nov 17;15:165. doi: 10.1186/s12871-015-0147-0.

DOI:10.1186/s12871-015-0147-0
PMID:26577339
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4647808/
Abstract

BACKGROUND

Previous studies showed that cyclooxygenase(COX) was involved in ischemia/reperfusion (I/R) injuries. Parecoxib, a selective inhibitor for COX -2, has been shown to have protective properties in reducing I/R injury in the heart, kidney and brain. The aim of this study was to investigate the effects of parecoxib on hepatic I/R and to explore the underlying mechanisms.

METHODS

Fifty-two Sprague-Dawley rats were randomly divided into three groups: the sham-operation (Sham) group, the hepatic ischemia/reperfusion (I/R) group, and the parecoxib pretreated I/R (I/R + Pare) group. Partial warm ischemia was produced in the left and middle hepatic lobes of Sprague-Dawley rats for 60 min, followed by 6 h of reperfusion. Rats in the I/R + Pare group received parecoxib (10 mg/kg) intraperitoneally twice a day for three consecutive days prior to ischemia. Blood and tissue samples from the groups were collected 6 h after reperfusion, and a survival study was performed.

RESULTS

Pretreatment with parecoxib prior to I/R insult significantly reduced I/R-induced elevations of aminotransferases, and significantly improved the histological status of the liver. Parecoxib significantly suppressed inflammatory cascades, as demonstrated by attenuations in TNF-α and IL-6. Parecoxib significantly inhibited iNOS and nitrotyrosine expression after I/R and significantly attenuated I/R-induced apoptosis. The 7-day survival rate was increased by pre-administration of parecoxib.

CONCLUSIONS

Administration of parecoxib prior to hepatic I/R attenuates hepatic injury through inhibition of inflammatory response and nitrosative stress.

摘要

背景

先前的研究表明，环氧化酶（COX）参与了缺血/再灌注（I/R）损伤。帕瑞昔布是一种COX-2选择性抑制剂，已被证明在减轻心脏、肾脏和大脑的I/R损伤方面具有保护作用。本研究的目的是探讨帕瑞昔布对肝脏I/R的影响，并探索其潜在机制。

方法

52只Sprague-Dawley大鼠随机分为三组：假手术（Sham）组、肝脏缺血/再灌注（I/R）组和帕瑞昔布预处理的I/R（I/R + Pare）组。对Sprague-Dawley大鼠的左肝中叶和中叶进行部分热缺血60分钟，然后再灌注6小时。I/R + Pare组的大鼠在缺血前连续三天每天腹腔注射帕瑞昔布（10mg/kg）两次。再灌注6小时后收集各组的血液和组织样本，并进行生存研究。

结果

在I/R损伤前用帕瑞昔布预处理可显著降低I/R诱导的转氨酶升高，并显著改善肝脏的组织学状态。帕瑞昔布显著抑制炎症级联反应，TNF-α和IL-6的减弱证明了这一点。帕瑞昔布在I/R后显著抑制iNOS和硝基酪氨酸表达，并显著减轻I/R诱导的细胞凋亡。预先给予帕瑞昔布可提高7天生存率。

结论

在肝脏I/R之前给予帕瑞昔布可通过抑制炎症反应和亚硝化应激减轻肝脏损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/fa713d1d130c/12871_2015_147_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/27d029e3e578/12871_2015_147_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/0c824fee273b/12871_2015_147_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/a5213fbfefab/12871_2015_147_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/87ea51f50981/12871_2015_147_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/59371127b569/12871_2015_147_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/fa713d1d130c/12871_2015_147_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/27d029e3e578/12871_2015_147_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/0c824fee273b/12871_2015_147_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/a5213fbfefab/12871_2015_147_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/87ea51f50981/12871_2015_147_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/59371127b569/12871_2015_147_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b30c/4647808/fa713d1d130c/12871_2015_147_Fig6_HTML.jpg

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