内毒素在肝胰岛素抵抗中对肝细胞线粒体功能的影响  

Effects of endotoxemia on hepatocytes mitochondrial function in hepatic insulin resistance

作　　者：王文递 林雅玲[1] 宋彬妤[1] 刘晓梁[1] 王明亮[1] 赵成瑞[2] 王旭文[3] 吴惠文[1] 

机构地区：[1]山西医科大学汾阳学院科技中心,山西汾阳032200 [2]山西医科大学汾阳学院生理教研室,山西汾阳032200 [3]中国石油天然气集团公司中心医院整形手外烧伤科,河北廊坊065000

出　　处：《中国医药导报》2017年第12期33-38,共6页China Medical Herald

基　　金：山西医科大学汾阳学院校级基金(1302)

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 300μg/(kg·d)。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达。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<0.01),胰岛素信号转导蛋白表达降低,UCP2表达升高(P<0.01);HFD组与LPS组上述指标变化差异无统计学意义(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或P<0.01),能量代谢异常(P<0.05),胰岛素信号转导蛋白表达下降,UCP2表达升高(P<0.05或P<0.01);各干预组之间以上指标变化差异无统计学意义(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。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 ~xg/（kg.d）]. 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 mea- sured. Western blot was used to detect the insulin signal transduction proteins and mitochondrial transmembrane pro- tein （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 contain- ing fructose water （4.5 g/L） and LPS （10 mg/L）. After 20 h, the mitochondrial function and protein expres-sion of insulin signal transduction were detected. Results Compared with NC group, the levels of plasma LPS, liver enzymes, HOMA-IR and oxidative damage products in HFD group and LPS group were significantly increased （P 〈 0.01）, energy metabolism was abnormal （P 〈 0.01）, insulin signal transduction protein expressions were decreased and UCP2 expressions were increased （P 〈 0.01）; these indexes had no significant differences between the HFD group and the LPS group （P 〉 0.05）. Compared with NC group, oxidative damage products of the cell supernatant in HFD group, LPS group and H＋L group were higher （P 〈 0.05 or P 〈 0.01）, energy metabolism was abnormal （P 〈 0.05）, insulin signal

关 键 词：内毒素血症 胰岛素抵抗 氧化应激 线粒体功能 

分 类 号：R33[医药卫生—人体生理学]