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目的:探讨沉默信息调节因子6（SIRT-6）低表达对单核细胞炎症反应及细胞自噬作用的调控作用。方法:人急性单核细胞白血病细胞株（THP-1）通过转染SIRT6基因感染慢病毒（si-SIRT6）建立SIRT-6低表达THP-1细胞株，将细胞分为对照组、尿酸盐（MUS）组和MUS+雷帕霉素（RAPA）组，对照组细胞加入PBS，MUS组细胞加入MUS，MUS+RAPA组细胞加入MUS和RAPA，各组细胞培养48 h，采用ELISA检测各组细胞上清液IL-1β、IL-6和TNF-α水平，采用定量聚合酶链反应（Q-PCR）检测各组细胞自噬相关蛋白-5（ATG-5）、重组人自噬效应蛋白（Beclin-1）、溶酶体相关膜蛋白-1（LAMP-1）、微管相关蛋白1轻链3B（LC3B）和p62基因表达水平，采用蛋白免疫印迹法检测各组细胞p62、ATG-5、LC3B Ⅱ/ LC3B Ⅰ蛋白表达水平。计量资料通过单因素方差分析（ANOVA）分析多组间数据的差异，组间比较采用LSD- t检验。 结果:si-SIRT-6转染组THP-1细胞SIRT-6基因和蛋白表达水平较空白病毒转染组显著降低（基因：1.09±0.08与0.57±0.03， t=14.91， P<0.001；蛋白：0.21±0.04与0.12±0.03， t=4.41， P=0.070）。MSU组si-SIRT6/空白病毒转染THP-1细胞上清液IL-1β、IL-6和TNF-α水平较对照组显著升高，并且MUS+RAPA组细胞上清液IL-1β、IL-6和TNF-α水平较MUS组进一步升高；si-SIRT6转染THP-1细胞上清液IL-1β、IL-6和TNF-α水平较空白病毒转染THP-1细胞显著升高。MSU组si-SIRT6/空白病毒转染THP-1细胞中p62基因表达水平较对照组显著降低，ATG-5、Beclin-1、LAMP-1和LC3B基因表达水平较对照组显著升高，并且MUS+RAPA组细胞中p62基因表达水平较MUS组进一步降低，ATG-5、Beclin-1、LAMP-1和LC3B基因表达水平较MUS组进一步升高；si-SIRT6转染THP-1细胞中p62基因表达水平较空白病毒转染THP-1细胞显著降低，ATG-5、LC3B、Beclin-1和LAMP-1基因表达水平较空白病毒转染THP-1细胞显著升高。MSU组si-SIRT6 /空白病毒转染THP-1细胞中P62蛋白表达水平较MUS组显著降低，ATG-5、LC3B蛋白表达水平较MUS组显著升高（ P<0.05），并且MUS+RAPA组细胞中P62蛋白表达水平较MUS组进一步降低，ATG-5、LC3B蛋白表达水平较MUS组进一步升高（ P<0.05）；si-SIRT6转染THP-1细胞中P62蛋白表达水平较空白病毒转染THP-1细胞显著降低，ATG-5、LC3B蛋白表达水平较空白病毒转染THP-1细胞显著升高。 结论:SIRT-6基因低表达可促进单核细胞炎症反应和细胞自噬作用，并且尿酸盐和自噬激动剂雷帕霉素可加重炎症反应和细胞自噬作用。

Objective:To investigate the effect of low expression of silencing information regulator-6 (SIRT-6) on inflammatory reaction and autophagy in monocytes.Methods:Human acute monocytic leukemia cell line THP-1 was transfected with si-SIRT6 to establish THP-1 cell line with low expressed SIRT-6. The cells were divided into control group, MUS group and MUS+ RAPA group. Cells in control group were cultured with medium added with PBS, cells in MUS Group were cultured with medium added with MUS, and cells in MUS+ RAPA Group were added with MUS and Rapamycin. Cells in each group were cultured for 48 hours. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the supernatant of each group were detected by enzyme-linked immunosorbent assay (ELISA). The gene expression levels of autophagy-associated protein-5 (ATG-5), Beclin-1, lysosomal-associated membrane protein-1 (LAMP-1), microtubule-associated protein-1 light chain 3B (LC3B) and p62 in cells of each group were detected by Q-PCR. The protein expression levels of p62, ATG-5 and LC3B Ⅱ/LC3BⅠ in cells of each group. The one-way analysis of variance (ANOVA) was used for the measurement data in multi-groups, and the LSD- t test was used for the measurement data in both groups. Results:The gene and protein expression of SIRT-6 in THP-1 cells decreased significantly after si-SIRT6 transfection (Gene: 1.09±0.08 vs. 0.57±0.03, t=14.91, P<0.001; Protein: 0.21±0.04 vs. 0.12±0.03, t=4.41, P=0.070). The levels of IL-1β, IL-6, and TNF-α in the supernatant of si-SIRT6/si-SIRT6 NC-transfected THP-1 cells increased significantly by MUS ( P<0.05), and the levels of IL-1β, IL-6, and TNF-α in the supernatant of cells further increased by MUS ( P<0.05). The levels of IL-1β, IL-6 and TNF-α in the supernatant of si-SIRT6-transfected THP-1 cells increased significantly compared with those of si-SIRT6 NC-transfected THP-1 cells ( P<0.05). The gene expression of p62 in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells significantly decreased by MUS ( P<0.05), the gene expression of ATG-5, Beclin-1, LAMP-1 and LC3B in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells significantly increased by MUS ( P<0.05). The gene expression of p62 in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells further decreased by RAPA ( P<0.05), the gene expression of ATG-5, Beclin-1, LAMP-1 and LC3B in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells further increased by RAPA ( P<0.05). The gene expression level of p62 in si-SIRT6 transfected THP-1 cells significantly decreased than that in si-SIRT6 NC transfected THP-1 cells ( P<0.05), and the gene expression level of ATG-5, LC3B, Beclin-1 and LAMP-1 significantly increased than that in si-SIRT6 NC transfected THP-1 cells ( P<0.05). The protein expression of p62 in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells significantly decreased by MUS ( P<0.05), the protein expression of ATG-5 and LC3B Ⅱ/LC3BⅠ protein in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells significantly increased by MUS ( P<0.05). The protein expression of p62 in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells further decreased by RAPA P<0.05), the protein expression of ATG-5 and LC3B Ⅱ/LC3BⅠ in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells further increased by RAPA ( P<0.05). The protein expression level of p62 in si-SIRT6 transfected THP-1 cells significantly decreased than that in si-SIRT6 NC transfected THP-1 cells ( P<0.05), and the protein expression level of ATG-5 and LC3B Ⅱ/LC3BⅠ significantly increased than that in si-SIRT6 NC transfected THP-1 cells ( P<0.05). Conclusion:Low expression of SIRT-6 gene can promote inflammatory reaction and autophagy in monocytes, and Monosodium urate and autophagy agonist rapamycin can aggravate inflammatory reaction and autophagy.