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Objective To investigate the relieving effects of knockdown of long non-coding RNA(lncRNA)taurine up-regulated gene 1 (TUG1) on inhibiting nucleotide binding oligomerization domain like receptor protein 1 (NLRP1) inflammasome and the progression of Alzheimer’ s disease. Methods Wild-type (WT group, 10 mice) or amyloid precursor protein (APP) / presenilin-1 (PS1) transgenic mice (30 mice) with a genetic background of C57 / BL6 aged 9-10 weeks were used in this study. APP / PS1 transgenic mice were randomly divided into model group, model+lncRNA TUG1 short hairpin RNA (shRNA) group and model + shRNA non target (NT) group (n = 10) . Blood samples, cerebral cortex tissues, primary microglial cells and primary astrocytes were collected from mice 12 weeks of age on day 1 (3-month-old) and 32 weeks of age on day 1 (8-month-old), with 5 mice per group at each time point. Real-time PCR analysis was used to detect the expression levels of lncRNA TUG1 and macrophage migration inhibitory factor (MIF) mRNA in cerebral cortex tissues and primary microglial cells, and C1r and C1s mRNA levels in primary astrocytes of 3-month-old and 8-month-old mice in the above 4 groups, respectively. ELISA was used to determine the MIF in plasma samples of the above 4 groups of mice. Primary microglia and astrocytes from the cerebral cortex of 3-month-old and 8-month-old mice were co-cultured. CCK-8 method was used to determine the proliferation ability of the above cells. Western blotting was used to determine the expression levels of MIF, pro interleukin-1β (pro-IL-1β), apoptosis associated speck-like protein containing a caspase recrult domain(ASC), Caspase-1 (p20), Caspase-1 (full), NLRP1 and NLRP3 in cerebral cortex tissues of 3-month-old and 8-month-old mice. Immunofluorescent staining was used to determine amyloid beta(Aβ) in cerebral cortex of 8-month-old mice. Results At the age of 3-month-old and 8-month-old, compared with the WT group, the relative expression level of lncRNA TUG1 and MIF in cerebral cortex tissues and primary microglia of model group mice was significantly up-regulated, with primary microglial cells and astrocytes proliferation ability enhanced (P0. 05) . There was no significant difference between the model group and the model+shRNA NT group mice of all the above factors (P>0. 05) . Conclusion In APP / PS1 transgenic mice, up-regulation of lncRNA TUG1 and MIF are positively associated with the activation of NLRP1 inflammasome in mice cerebral cortex tissues and primary microglia. Knock-down of lncRNA TUG1 can ameliorate the progression of Alzheimer’ s disease.
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Objective: To study the relationship between sterol regulatory element binding protein-1 (SREBP-1) and nucleotide-binding oligomerization domain-like receptor protein-1 (NLRP-1) inflammasome in patients with coronary artery disease (CAD). Methods: Our research included in 3 groups: Control group, n=20 normal subjects, SAP (stable angina pectoris) group, n=49 and ACS (acute coronary syndrome) group, n=55. Plasma levels of IL-1β, IL-18 and hs-CRP were examined by ELISA, mRNA and protein expressions of SREBP-1, NLRP-1 and Caspase-1 in peripheral blood mononuclear cells (PBMC) were detected by RT-PCR and Western blot analysis. Relationships between SREBP-1 and NLRP1, Caspase-1, IL-1β, IL-18 were studied. Results: Compared with Control group, ACS group and SAP group had increased plasma levels of IL-1β, IL-18 and hs-CRP, all P<0.05; elevated mRNA and protein expressions of SREBP-1, NLRP-1 and Caspase-1 in PBMC, in addition, those expressions in ACS group was even higher than SAP group, all P<0.05. SREBP-1 level was positively related to NLRP1, Caspase-1, IL-1β and IL-18, all P<0.05. Conclusion: The expressions of SREBP-1 and NLRP1 inflammasome were increased in CAD patients; SREBP-1 and NLRP1 had positive correlation.