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

吲哚美辛对小鼠肾缺血再灌注损伤的保护作用(英文)

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 a （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 F1α. 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.

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5 mg/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7 mg/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5 mg/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5 mg/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。