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L. Nežić, R. Škrbić, L. Amidžić
0 2018.

Simvastatin protects against endotoxin induced acute lung injury and apoptosis via activation of survivin/NF-κB signaling pathway

Background: It is considered that acute lung injury (ALI) is an uncontrolled inflammation, mainly attributed to the release of inflammatory mediators and extensive apoptosis. Aim: As simvastatin exerts antiinflammatory properties by regulating cellular signaling pathways, we explored its effects on ALI development and apoptotosis of immune and epithelial cells in endotoxic shock. Methods: Male Wistar rats were intraperitoneally injected with 0.25 of the medial lethal dose of endotoxin (lipopolysaccharide, LPS). Simvastatin was given orally (10, 20, 40 mg/kg, per group) as a five-day pre-treatment prior to a single dose of LPS, and 48 afterwards the animals were sacrificed. Lung tissue inflammatory damage was assessed by histopathological examination (haematoxylin-eosin staining), and expressed as a tissue damaged score (TDS). Apoptosis was analysed by TUNEL (DNA fragmentation assay) and expressed as an apoptotic index (AI), and immunohistochemically by detection of cleaved caspase-3, Bcl-XL, inhibitor of apoptosis, survivin as well as expression of nuclear factor (NF)- κB signalling pathway. Results: TDSs showed that simvastatin ameliorated ALI induced by LPS in dose-dependent manner (simvastatin 20 mg/kg and 40 mg/kg vs LPS, 2.0±0.59 and 1.33±0.48 vs 3.35 ±0.42, p<0.01, respectively). LPS induced significant apoptosis (AI 43.8%±11.3), and increased expression of cleaved caspase-3


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