荜茇酰胺改善睡眠剥夺诱发的小鼠肝脂肪变性的作用  

Effects of piperlongumine on liver steatosis induced by sleep deprivation in mice

作　　者：刘滢 黄燕花 程创[1] 熊伟[1] 侯良绢[1] LIU Ying;HUANG Yan-hua;CHENG Chuang;XIONG Wei;HOU Liang-juan(Anatomy Teaching and Research Section,Chongqing Three Gorges Medical College,Chongqing 404120,China;Department of Infection,Three Gorges Hospital Afiliated to Chongqing University,Chongqing 404100,China)

机构地区：[1]重庆三峡医药高等专科学校解剖学教研室,重庆404120 [2]重庆大学附属三峡医院感染科,重庆404100

出　　处：《中国临床药理学杂志》2025年第5期691-695,共5页The Chinese Journal of Clinical Pharmacology

基　　金：重庆市教育委员会科学技术研究基金资助项目(KJQN202002711)。

摘　　要：目的探究荜茇酰胺对睡眠剥夺诱发的肝脂肪变性的影响及其作用机制。方法将小鼠随机分为对照组(正常饲养)、模型组(睡眠剥夺处理)和低、中、高剂量组(睡眠剥夺的基础上分别给予2.5、5.0和10.0 mg·kg^(-1)荜茇酰胺),连续灌胃14 d。治疗后,检测小鼠肝指数,用蛋白质印迹实验检测肝组织中蛋白表达,用试剂盒检测组织中脂质水平,用超氧化物阴离子荧光探针(DHE)法检测肝组织活性氧(ROS)水平。结果对照组、模型组、高剂量组肝指数分别为(2.99±0.40)%、(4.32±0.17)%和(3.30±0.37)%,三酰甘油(TG)水平分别为(0.16±0.01)、(0.29±0.02)和(0.17±0.02)mmol·mgprot^(-1),脂肪酸合成酶(FAS)蛋白水平分别为0.31±0.03、0.69±0.08和0.35±0.03,缺氧诱导因子-1α(HIF-1α)蛋白水平分别为0.38±0.04、0.94±0.08和0.44±0.04,衔接蛋白p66Shc(p66Shc)蛋白水平分别为0.21±0.03、0.82±0.07和0.37±0.04,ROS水平分别为1.00±0.09、4.72±0.44和1.30±0.07。模型组的上述指标与对照组比较,高剂量组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论荜茇酰胺可改善睡眠剥夺诱导的小鼠肝脂肪变性,这可能与调节HIF-1α/p66Shc信号通路有关。Objective To explore the effect and mechanism of piperlongumine on hepatic steatosis induced by sleep deprivation.Methods Mice were randomly divided into control group(normal feeding),model group(sleep deprivation treatment),low-,middleand high dose groups(2.5,5.0 and 10.0 mg·kg^(-1)piperlongumine was given on the basis of sleep deprivation),and the mice were given continuous gavage for 14 days.Liver index was detected after 14 days o continuous gavage.Western blot assay was used to detect protein expression in hepatic tissue,lipid levels in hepatic tissue were detected by kit,and reactive oxygen species(ROS)levels in hepatic tissue were detected by dihydroethidium(DHE).Results The liver index of control group,model group,and high-dose group were(2.99±0.40)%,(4.32±0.17)%and(3.30±0.37)%,respectively;triglyceride(TG)levels were(0.16±0.011),(0.29±0.02)and(0.17±0.02)mmol·mgprot^(-1),respectively;fatty acid synthase(FAS)protein levels were 0.31±0.03,0.69±0.08 and 0.35±0.03,respectively;hypoxiainducing factor-1α(HIF-1α)protein levels were 0.38±0.04,0.94±0.08 and 0.44±0.04,respectively;the protein levels of adaptor p66Shc(p66Shc)were 0.21±0.03,0.82±0.07 and 0.37±0.04,respectively;ROS levels were 1.00±0.09,4.72±0.44 and 1.30±0.07,respectively.The above indexes in the model group were significantly different from those in the control group,and the above indexes in the high-dose groups were significantly different from those in the model group(allP<0.05).Conclusion Piperlongumine can improve liver steatosis induced by sleep deprivation in mice,which may be related to the regulation of HIF-1α/p66Shc signaling pathway.

关 键 词：荜茇酰胺 睡眠剥夺 肝脂肪变性 缺氧诱导因子-1α/衔接蛋白p66Shc信号 线粒体功能 

分 类 号：R28[医药卫生—中药学]