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.
Background and aims： Ingestion of paraquat （PQ）, a widely used herbicide, can cause severe toxicity in humans, leading to a poor survival rate and prognosis. One of the main causes of death by PQ is PQ-induced pul- monary fibrosis, for which there are no effective therapies. The aim of this study was to evaluate the effects of ra- pamycin （PAPA） on inhibiting PQ-induced pulmonary fibrosis in mice and to explore its possible mechanisms. Methods： Male C57BL/6J mice were exposed to either saline （control group） or PQ （10 mg/kg body weight, intraper- itoneally; test group）. The test group was divided into four subgroups： a PQ group （PQ-exposed, non-treated）, a PQ＋RAPA group （PQ-exposed, treated with RAPA at I mg/kg intragastrically）, a PQ＋MP group （PQ-exposed, treated with methylprednisolone （MP） at 30 mg/kg intraperitoneally）, and a PQ＋MP＋RAPA group （PQ-exposed, treated with MP at 30 mg/kg intraperitoneally and with PAPA at 1 mg/kg intragastrically）. The survival rate and body weight of all the mice were recorded every day. Three mice in each group were sacrificed at 14 d and the rest at 28 d after intox- ication. Lung tissues were excised and stained with hematoxylin-eosin （H＆E） and Masson＇s trichrome stain for his- topathological analysis. The hydroxyproline （HYP） content in lung tissues was detected using an enzyme-linked im- munosorbent assay （ELISA） kit. The expression of transforming growth factor-β1 （TGF-β1） and α-smooth muscle actin （α-SMA） in lung tissues was detected by immunohistochemical staining and Western blotting. Results： A mice model of PQ-induced pulmonary fibrosis was established. Histological examination of lung tissues showed that PAPA treatment moderated the pathological changes of pulmonary fibrosis, including alveolar collapse and interstitial collagen depo- sition. HYP content in lung tissues increased soon after PQ intoxication but had decreased significantly by the 28th day after PAPA treatment. Immunohistoche
