肝细胞特异性Sirt1缺失加重小鼠肝脏炎性反应

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。

Hepatocyte-specific Sirt1 deficiency exacerbates liver inflammation of mice

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.