沉默信息调节因子2相关酶1通过增强肝X受体及抑制核因子κB信号起到抗动脉粥样硬化作用

SIRT1 Prevents Atherosclerosis Through both Liver-X-Receptor and NF-κB Signaling

目的：探讨冠状动脉粥样硬化患者外周血单个核细胞（PBMCs）中沉默信息调节因子2相关酶1（SIRT1）与肝X受体（LXR）-趋化因子受体7（CCR7）/ATP联结盒转运因子A1（ABCA1）及炎症信号核因子κB（NF-κB）的关系。方法抽取104名正常人（NC组）以及111例冠状动脉粥样硬化患者（AS组）外周血，提取PBMCs，用实时荧光定量多聚酶链反应（qPCR）检测PBMCs中SIRT1、LXR及其下游CCR7/ ABCA1和促炎症信号NF-κB及其下游肿瘤坏死因子（TNF-α）的相对mRNA水平，并收集相关临床数据。所有数据应用SPSS 20.0统计软件进行分析。结果 qPCR结果显示所有AS组患者PBMCs中的SIRT1、LXR及其下游因子CCR7、ABCA1 mRNA含量比NC组低，差异具有统计学意义（P＜0.05）；而NF-κB及其下游因子TNF-α mRNA含量高于NC组（P＜0.05）。相关性分析显示LXR mRNA与HDL呈正相关（P＜0.01， r=0.22），NF-κB、TNF-αmRNA与单核细胞数量呈正相关（P＜0.05，r=0.31，0.23）。结论 SIRT1可能通过抑制NF-κB信号及增强LXR-CCR7/ABCA1信号，抑制炎症，促进胆固醇流出，甚至激活单核-巨噬细胞源性泡沫细胞移出动脉粥样硬化斑块的潜能，从而起到抑制动脉粥样硬化发展甚至逆转动脉粥样硬化的作用。

Objective To explore the association of silent information regulator 1 （SIRT1） with liver-X-receptor （LXR） and NF-κB signaling in peripheral blood mononuclear cell （PBMC） of patient with atherosclerosis.MethodsPeripheral blood and biochemical data were collected from 104 healthy individuals （normal control group, NC group） and 111 cases of patients with coronary atherosclerotic heart disease admitted for cardiac catheterization （atherosclerosis group, AS group）. Real-time Quantitative polymerase chain reaction （qPCR） was used to detect SIRT1, LXR, CCR7, ABCA1, NF-κB and TNF-α mRNA levels in PBMC.Results PCR showed that SIRT1, LXR, ABCA1, CCR7 mRNA levels in AS group were lower than those in NC group （P〈0.05）, NF-κB and TNF-αmRNA levels in AS group were higher than those in NC group. Correlation analysis showed that there is a positive correlation between LXR mRNA levels and HDL （P〈0.01,r=0.22）, a positive correlation between NF-κB, TNF-α mRNA levels and monocytes （P〈0.05,r=0.31 and 0.23）.Conclusion Our present study indicates that SIRT1 may prevent atherosclerosis through up-regulating LXR-CCR7/ABCA1 signaling and inhibiting NF-κB -mediated inflammatory signaling.