肝细胞特异性Sirt1缺失加重小鼠肝脏炎性反应  

Hepatocyte-specific Sirt1 deficiency exacerbates liver inflammation of mice

作　　者：杨佳卉 赵微 解相宏 李春美 刘晓军 姚红[1] YANG Jia-hui;ZHAO Wei;XIE Xiang-hong;LI Chun-mei;LIU Xiao-jun;YAO Hong(Department of Microbiology and Immunology, Basic Medicine College, Shanxi Medical University, Taiyuan 030001;National Key Laboratory of Medical Molecular Biology, Insititute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC, Beijing 100005, China)

机构地区：[1]山西医科大学基础医学院微生物学与免疫学教研室,山西太原030001 [2]中国医学科学院基础医学研究所,北京协和医学院基础学院,医学分子生物学国点重点实验室,北京100005

出　　处：《基础医学与临床》2022年第2期282-285,共4页Basic and Clinical Medicine

摘　　要：目的探究沉默信息调节因子1(Sirt1)基因的缺失对小鼠肝脏炎性反应的影响及其作用机制。方法每周记录在高脂喂养下的野生型C57BL/6J雄性小鼠和肝脏特异性Sirt1敲除(Sirt1-LKO)雄性小鼠的体质量,用Western blot和q-PCR检测炎性因子的表达;给小鼠腹腔注射20 mg/kg LPS,用生存曲线来反映小鼠对炎性反应的敏感性。结果与对照组WT小鼠相比,Sirt1-LKO小鼠表现为体质量明显减轻(P<0.05)。另外,生存曲线KaplaneMeier图显示Sirt1-LKO小鼠对LPS刺激呈现低敏感性(P<0.05)。Sirt1-LKO小鼠原代肝细胞中NF-κB蛋白水平增高(P<0.05),及NF-κB下游靶基因炎性因子Tnfα和IL6明显上调(P<0.05)。结论肝细胞特异性Sirt1缺失加重肝脏炎性反应。Objective To investigate the effect of deletion of Sirtuin type 1(Sirt1)gene on liver inflammation of mice and its mechanism.Methods The body weight of C57BL/6J male mice and liver specific Sirt1 deficiency(Sirt1-LKO)male mice were recorded weekly.The sensitivity of inflammatory response was tested by intraperitoneal injection of 20 mg/kg LPS.The survival curve was used to reflect the sensitivity of mice to inflammatory response.The expression of inflammatory factors was detected by Western blot and q-PCR.ResultsCompared with control wild type mice,Sirt1-LKO mice showed significantly reduced body weight(P<0.05).In addition,The survival curve was shown by kaplane Meier diagram,Sirt1-LKO mice showed lower sensitivity to LPS(P<0.05).The protein level of NF-κB in primary liver cells of Sirt1-LKO mice was increased(P<0.05),Tnfαand IL6 of NF-κB downstream target genes were up-regulated(P<0.05).Conclusions Hepatocyte-specific Sirt1 deletion aggravates liver inflammation response in mouse model.

关 键 词：SIRT1 肝细胞炎性反应 NF-ΚB 

分 类 号：R575.1[医药卫生—消化系统]