内毒素在肝胰岛素抵抗中对肝细胞线粒体功能影响.docVIP

内毒素在肝胰岛素抵抗中对肝细胞线粒体功能影响 　　[摘要] 目的 研究果糖饮食及皮下注射内毒素（LPS）致大鼠肝胰岛素抵抗（IR）及内毒素血症中，LPS对肝细胞线粒体功能的影响。 方法 30只SD雄性大鼠随机分为三组。对照组（NC组）：普通饲料喂养；果糖组（HFD组）：10%果糖水喂养；LPS组：皮下注射LPS 300 μg/（kgd）。8周糖耐量实验后，检测血浆肝酶、空腹胰岛素、LPS变化，计算IR指数；检测肝组织氧化损伤及能量代谢指标；Western blot检测肝组织胰岛素信号转导蛋白及线粒体内膜蛋白（UCP2）表达；观察肝组织病理学变化。分离培养大鼠肝细胞分为四组。NC组：DMEM培养液培养；HFD组：培养液+果糖水（4.5 g/L）；LPS组：培养液+LPS（10 mg/L）；果糖+LPS组（H+L组）：培养液+果糖水（4.5 g/L）+LPS（10 mg/L）。20 h后，检测肝细胞线粒体功能及胰岛素信号转导蛋白表?_。 结果 与NC组比较，HFD组与LPS组LPS、肝酶及氧化损伤产物显著升高，能量代谢异常（P 0.05）。HFD组、LPS组和H+L组细胞上清液氧化损伤产物高于NC组（P 0.05）。 结论 果糖饮食及皮下注射LPS致大鼠肝IR中，伴有内毒素血症。LPS可促发肝氧化应激，影响肝细胞线粒体功能，促进代谢性疾病的发生 [关键词] 内毒素血症；胰岛素抵抗；氧化应激；线粒体功能 [中图分类号] R33 [文献标识码] A [文章编号] 1673-7210（2017）04（c）-0033-06 [Abstract] Objective To study the effect of LPS on hepatic mitochondrial function in rats with hepatic insulin resistance （IR） and endotoxemia caused by fructose diet and subcutaneous injection of endotoxin. Methods 30 SD male rats were randomly divided into three groups. The control group （NC group）， fed with the general feeding； fructose group （HFD group）， fed with 10% fructose water； LPS group was administered subcutaneously with LPS [300 μg/（kgd）]. 8 weeks later， glucose tolerance test was measured， the changes of liver enzymes， fasting plasma insulin and LPS were detected， and HOMA-IR was calculated. The indexes of hepatic oxidative damage and energy metabolism were measured. Western blot was used to detect the insulin signal transduction proteins and mitochondrial transmembrane protein （UCP2） in hepatic tissue. The pathological changes of liver tissue were observed. Rat hepatocytes were isolated and divided into four groups： NC group incubated with DMEM medium； HFD group incubated with medium containing fructose water （4.5 g/L）； LPS group incubated with medium containing LPS （10 mg/L）； fructose + LPS group （H + L group） incubated with medium containing fructose water （4.5 g/L） and LPS （10 mg/L）. After 20 h， the mitochondrial function and protein expression of insulin signal transduction were dete