Journal of Zhejiang University

Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.8 P.735-742

Protective effect of indomethacin in renal ischemia-reperfusion injury in mice*

Author(s): Sheng-hong Zhu^1,2,Li-jia Zhou¹,Hong Jiang¹,Rong-jun Chen¹,Chuan Lin¹,Shi Feng¹,Juan Jin¹,Jiang-hua Chen¹,Jian-yong Wu¹
Affiliation(s): 1. 1. Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China more
Corresponding email(s): wujianyong@medmail.com.cn
Key Words: Non-steroidal anti-inflammatory drug (NSAID), Indomethacin (IMT), Ischemia-reperfusion injury (IRI), Dosage, Protective effect

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Sheng-hong Zhu, Li-jia Zhou, Hong Jiang, Rong-jun Chen, Chuan Lin, Shi Feng, Juan Jin, Jiang-hua Chen, Jian-yong Wu. Protective effect of indomethacin in renal ischemia-reperfusion injury in mice[J]. Journal of Zhejiang University Science B, 2014, 15(8): 735-742.

@article{title="Protective effect of indomethacin in renal ischemia-reperfusion injury in mice",
author="Sheng-hong Zhu, Li-jia Zhou, Hong Jiang, Rong-jun Chen, Chuan Lin, Shi Feng, Juan Jin, Jiang-hua Chen, Jian-yong Wu",
journal="Journal of Zhejiang University Science B",
volume="15",
number="8",
pages="735-742",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300196"
}

%0 Journal Article
%T Protective effect of indomethacin in renal ischemia-reperfusion injury in mice
%A Sheng-hong Zhu
%A Li-jia Zhou
%A Hong Jiang
%A Rong-jun Chen
%A Chuan Lin
%A Shi Feng
%A Juan Jin
%A Jiang-hua Chen
%A Jian-yong Wu
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 8
%P 735-742
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300196

TY - JOUR
T1 - Protective effect of indomethacin in renal ischemia-reperfusion injury in mice
A1 - Sheng-hong Zhu
A1 - Li-jia Zhou
A1 - Hong Jiang
A1 - Rong-jun Chen
A1 - Chuan Lin
A1 - Shi Feng
A1 - Juan Jin
A1 - Jiang-hua Chen
A1 - Jian-yong Wu
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 8
SP - 735
EP - 742
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300196

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Objective: To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs (NSAIDs) in renal ischemia-reperfusion injury (IRI) and the cyclooxygenase (COX)-1/2 blockade association by indomethacin (IMT) in the mice model. Methods: After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses: 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine (SCr) using enzyme-linked immunosorbent assay (ELISA) kits. Kidney samples were analyzed by hematoxylin and eosin (H&E) and immunohistochemistry stainings. Results: The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage. The tumor necrosis factor α (TNF-α) activity in renal homogenates and interleukin 6 (IL-6) activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B₂ to 6-keto-prostaglandin F_1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions: There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.

吲哚美辛对小鼠肾缺血再灌注损伤的保护作用

研究目的：在小鼠模型中利用吲哚美辛阻断COX-1/2通路，探讨非甾体类抗炎药对肾缺血再灌注损伤的保护作用。
创新要点：非甾体类抗炎药被认为具有肾毒性，本研究首次在小鼠模型中探讨非甾体类抗炎药对肾缺血再灌注损伤的保护作用。
研究方法：小鼠左侧肾蒂夹闭后，通过腹腔注射不同剂量的吲哚美辛，在肾缺血再灌注损伤24小时后，获取血液和肾脏标本。利用酶联免疫（ELISA）试剂盒测定血清肌酐和细胞因子浓度来评估肾功能，肾组织样本进行苏木精-伊红染色和免疫组化分析。
重要结论：腹腔注射吲哚美辛5mg/kg组的小鼠血清肌酐值与对照组相比显著降低，肾小管损伤也显著减轻（见图1和2）；腹腔注射5和7mg/kg吲哚美辛组的小鼠血清肾肿瘤坏死因子-α和白介素-6的浓度显著降低（见图3a和3b）；腹腔注射3和5mg/kg吲哚美辛组的小鼠血清血栓素B2与6-酮前列腺素F1α的比值明显降低（见图3c）；腹腔注射5mg/kg吲哚美辛组小鼠肾组织COX-1和COX-2染色较弱（见图4）。因此，吲哚美辛对小鼠肾缺血再灌注损伤的作用与其剂量相关，在某个特定的剂量范围内具有肾保护作用。吲哚美辛对小鼠肾缺血再灌注损伤的保护作用与阻断COX-1/2有关。
非甾体类抗炎药；吲哚美辛；缺血再灌注损伤；剂量；保护作用