SIRT1激活剂通过TLR4/NF-κB信号通路改善慢性牙周炎小鼠的炎症反应  

The effect of SIRT1 activator on inflammatory response in chronic Periodontal disease mice through TLR4/NF-κB signaling pathway

作　　者：马永臻 聂玉鹏 郝英魁 贾婧[1] Ma Yongzhen;Nie Yupeng;Hao Yingkui;Jia Jing(Department of Stomatology,the Affiliated Taian City Central Hospital of Qingdao University,Taian 271099,China)

机构地区：[1]青岛大学附属泰安市中心医院口腔科,泰安271099

出　　处：《中国医师杂志》2023年第7期1046-1050,共5页Journal of Chinese Physician

摘　　要：目的探索沉默信息调节因子1(SIRT1)激活剂SRT1720对于慢性牙周炎小鼠炎症反应的作用以及其机制是否与Toll样受体4(TLR4)/核因子κB(NF-κB)信号通路有关。方法选取8周龄的雄性C57BL/6小鼠40只,分为空白对照组(n=8)和实验组(n=32)。实验组小鼠结扎牙周袋并给予高糖饮用水喂养,实验组再随机分为模型组(n=8)和SRT1720组(n=24),空白对照组和模型组每天生理盐水灌胃,SRT1720组根据SRT1720剂量不同又分为低剂量组[20 mg/(kg·d),n=8]、中剂量组[50 mg/(kg·d),n=8]和高剂量组[100 mg/(kg·d),n=8]。4周后,ELISA法检测各组小鼠龈沟液中白介素-6(IL-6)、白介素-1β(IL-1β)、单核细胞趋化蛋白1(MCP-1)表达水平;RT-qPCR法检测各组小鼠牙龈组织IL-6、IL-1β、MCP-1、SIRT1、TLR4、NF-κB p65的mRNA表达水平;Western blot测定小鼠牙龈组织中SIRT1、TLR4、NF-κB p65蛋白表达水平。结果与空白对照组比较,实验组小鼠龈沟液中IL-6、IL-1β、MCP-1炎症因子表达水平升高,牙龈组织中IL-6、IL-1β、MCP-1、TLR4、NF-κB p65 mRNA表达水平升高,牙龈组织中TLR4、NF-κB p65蛋白表达水平升高,牙龈组织中SIRT1 mRNA和蛋白表达水平下降,差异均有统计学意义(均P<0.05)。与模型组比较,SRT1720组小鼠龈沟液中IL-6、IL-1β、MCP-1炎症因子表达水平,牙龈组织中IL-6、IL-1β、MCP-1、TLR4、NF-κB p65 mRNA表达水平及牙龈组织中TLR4、NF-κB p65蛋白表达水平均呈剂量依赖性下降,牙龈组织中SIRT1 mRNA和蛋白表达水平呈剂量依赖性升高,差异均有统计学意义(均P<0.05)。结论SIRT1激活剂SRT1720可以改善慢性牙周炎小鼠的炎症反应,这可能与抑制TLR4/NF-κB信号通路有关。Objective To explore the effect of silent information regulator 1(SIRT1)activator SRT1720 on inflammatory response in chronic periodontal disease mice and whether its mechanism is related to the toll like receptor 4(TLR4)/nuclear factorκB(NF-κB)signaling pathway.Methods Forty 8-week-old male C57BL/6 mice were selected and divided into a blank control group(n=8)and an experimental group(n=32).The experimental group mice were ligated with periodontal pockets and fed with high sugar drinking water.The experimental group was randomly divided into a model group(n=8)and an SRT1720 group(n=24).The blank control group and the model group were given physiological saline orally every day.The SRT1720 group was further divided into a low dose group[20 mg/(kg·d),n=8],a medium dose group[50 mg/(kg·d),n=8],and a high dose group[100 mg/(kg·d),n=8]based on the different doses of SRT1720.Four weeks later,the expression levels of interleukin-6(IL-6),interleukin-1β(IL-1β)and monocyte chemoattractant protein-1(MCP-1)in gingival crevicular fluid of mice in each group were detected by enzyme linked immunosorbent assay(ELISA);The real-time quantitative polymerase chain reaction(RT-qPCR)method was used to detect the mRNA expression levels of IL-6,IL-1β,MCP-1,SIRT1,TLR4,NF-kB p65 in the gingival tissue of mice in each group;Western blot was used to determine the expression levels of SIRT1,TLR4,and NF-κB p65 proteins in mouse gingival tissue.Results Compared with the blank control group,the expression levels of IL-6,IL-1β,and MCP-1 inflammatory factors in the gingival crevicular fluid of experimental group mice increased,while the expression levels of IL-6,IL-1β,MCP-1,TLR4,NF-κB p65 mRNA in gingival tissue increased.The expression levels of TLR4,NF-κB p65 protein in gingival tissue increased,while the expression levels of SIRT1 mRNA and protein in gingival tissue decreased,with statistical significance(all P<0.05).Compared with the model group,the expression levels of IL-6,IL-1β,and MCP-1 inflammatory factors in the gingival

关 键 词：慢性牙周炎 沉默信息调节因子1 TOLL样受体4 NF-ΚB 

分 类 号：R781.42[医药卫生—口腔医学]