基础医学与临床 ›› 2022, Vol. 42 ›› Issue (2): 282-285.doi: 10.16352/j.issn.1001-6325.2022.02.007

• 研究论文 • 上一篇    下一篇

肝细胞特异性Sirt1缺失加重小鼠肝脏炎性反应

杨佳卉1, 赵微2, 解相宏2, 李春美2, 刘晓军2, 姚红1*   

  1. 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
  • 收稿日期:2021-10-14 修回日期:2021-12-06 出版日期:2022-02-05 发布日期:2022-01-24
  • 通讯作者: * yyao1976@126.com

Hepatocyte-specific Sirt1 deficiency exacerbates liver inflammation of mice

YANG Jia-hui1, ZHAO Wei2, XIE Xiang-hong2, LI Chun-mei2, LIU Xiao-jun2, YAO Hong1*   

  1. 1. Department of Microbiology and Immunology, Basic Medicine College, Shanxi Medical University, Taiyuan 030001;
    2. National Key Laboratory of Medical Molecular Biology, Insititute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China
  • Received:2021-10-14 Revised:2021-12-06 Online:2022-02-05 Published:2022-01-24
  • Contact: * yyao1976@126.com

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。

关键词: Sirt1, 肝细胞炎性反应, NF-κB

Abstract: 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. Results Compared 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),Tnfα and 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.

Key words: Sirt1, hepatocyte inflammation response, NF-κB

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