ABSTRACT
Objective To evaluate the effect of resveratrol on mitochondrial function in renal tubular epithelial cells of rats with sepsis-induced acute kidney injury.Methods Ninety-six healthy SpragueDawley rats of both sexes,aged 5-7 weeks,weighing 180-220 g,were divided into 4 groups (n =24 each) using a random number table method:sham operation group (Sham group),sepsis group (group Sep),sepsis plus vehicle group (Sep+Ⅴ group) and sepsis plus resveratrol group (Sep+R group).Sepsis was induced by cecal ligation and puncture (CLP).Normal saline 0.5 ml,vehicle 0.5 ml and resveratrol 10 mg/kg were intraperitoneally injected at 6,12 and 18 h after CLP in Sep,Sep+Ⅴ and Sep+R groups,respectively.At 24 h after CLP,serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were measured,and kidney tissues were obtained for examination of the pathological changes (using transmission electron microscopy),and the damage to the renal tubules was scored.The renal tubular epithelial cells (RTECs) were isolated from the kidney cortex at 24 h after CLP for determination of mitochondrial transmembrane potential (by flow cytometry with the fluorescent probe JC-1),intracellular ATP content,mitochondrial permeability transition pore (mPTP) opening,lipid peroxide (LPO) content,and lysosomal membrane permeability.Results Compared with group Sham,the serum concentrations of Cr and BUN,renal tubular damage score,mPTP opening,LPO content and lysosomal membrane permeability were significantly increased,and mitochondrial transmembrane potential and ATP content were decreased in Sep and Sep+Ⅴ groups (P＜0.01).Compared with Sep and Sep+Ⅴ groups,the serum concentrations of Cr and BUN,renal tubular damage score,mPTP opening,LPO content and lysosomal membrane permeability were significantly decreased,and mitochondrial transmembrane potential and ATP content were increased in group Sep+R (P＜0.05).Conclusion Resveratrol improves mitochondrial function in renal tubular epithelial cells of rats with sepsis and reduces acute kidney injury,and the mechanism may be related to inhibiting oxidative stress and decreasing the lysosomal membrane permeability.