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circ-Sirt1抑制NF-κB核转位的机制及在血管炎症中的意义

发布时间:2021-11-01 15:59
  目的:动脉粥样硬化和血管退行性病变是导致心血管疾病的主要病因。炎症反应是导致动脉粥样硬化和血管退行性病的病理基础。本研究以SIRT1基因外显子来源的环状非编码RNA circ-Sirt1为研究对象,从整体、细胞和分子水平,探讨circ-Sirt1在血管炎症应答中的作用和分子机制。方法:利用野生型SD大鼠建立颈动脉损伤狭窄模型,采用实时荧光定量PCR和Western blot方法评价circ-Sirt1与血管炎症损伤的关系。利用Rip和RNA pull-down结合Western blot技术发现并验证与circ-Sirt1相互作用的蛋白。从RNA与蛋白质互作角度探讨circ-Sirt1对NF-κB p65活化及核转位的影响。结果:1 circ-Sirt1参与VSMCs表型调节1.1 RT-PCR筛选人SIRT1基因产生的环状RNA通过对环状RNA数据库circBase搜索,发现人SIRT1基因能产生11种环状RNA产物,RT-PCR检测11种环状RNA在人VSMCs中的表达情况。结果显示,hascirc0093887(circ-Sirt1)表... 

【文章来源】:河北医科大学河北省

【文章页数】:91 页

【学位级别】:博士

【部分图文】:

circ-Sirt1抑制NF-κB核转位的机制及在血管炎症中的意义


SIRT1基因编码产生的circRNAsFig.1-1ExpressionpatternofcircRNAisoformsproducefromSIRT1hostgene(A)RT-PCRswereconductedtodetecttheexpressionofcircRNAisoforms

序列同源性


21图 1-2 circ-sirt1 序列同源性比较Fig.1-2 circ-Sirt1 gene homology comparisoncirc-Sirt1 homology analysis in rat and human genome was conducted usingBasic Local Alignment Search Tool (BLAST).

血管平滑肌细胞,表型转化


22图 1-3 circ-sirt1 参与血管平滑肌细胞表型转化Fig.1-3 The expression of circ-Sirt1 is associated with phenotypic switching oVSMCs(A) qRT-PCRs were conducted to detect circ-Sirt1 expression in different rtissues. Data are summarized as mean±SEM, n=6.(B) qRT-PCRs were conducted to detect circ-Sirt1 expression in cells frodifferent sources, including HUVECs, HASMCs and RASMCs. Data asummarized as mean±SEM, n=4.(C, D and E) qRT-PCRs were conducted to detect circ-Sirt1 expression


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