过表达Nampt通过激活NF-κB诱导心肌细胞肥大

摘要

Aim To examine the effect of Nampt over-expression on cardiac hypertrophy,and elucidate the role of NF-κB.Methods The cultured neonatal car-diomyocytes were pretreated with 100 μmol · L-1 PE or transfected with Nampt.The mRNA and protein ex-pression of Nampt were determined by Real-time PCR and Western blot respectively.The cardiomyocyte hy-pertrophy was monitored by measuring cell-surface area and the mRNA levels of ANP and BNP,which were biomarkers of hypertrophic response.Moreover,we te-sted the effects of Nampt on NF-κB-dependent tran-scription activity through luciferase reporter gene as-says.Results Nampt overexpression significantly in-creased cardiomyocyte surface area and the mRNA ex-pression of ANP and BNP.In addition,Nampt overex-pression could markedly increase NF-κB-dependent transcription activity. Moreover, when p65 was knocked down,cardiomyocytes with Nampt overexpres-sion could not induce cardiac hypertrophy.Conclusion Overexpression of Nampt induces cardiac hypertro-phy by increasing NF-κB-dependent transcription activ-ity.%目的：研究过表达尼克酰胺磷酸核糖转移酶（nicotin-amide phosphoribosyltransferase，Nampt）对心肌细胞肥大的影响，并初步探讨NF-κB在其中的作用。方法心肌细胞给予苯肾上腺素（PE ）或过表达 Nampt 处理，采用 Real-time PCR检测Nampt、ANP和BNP的mRNA表达，利用 Western blot检测Nampt的蛋白水平，使用免疫荧光检测心肌细胞表面积，采用双荧光素酶报告基因的方法检测NF-κB依赖的转录活性。结果过表达Nampt能够诱导ANP和BNP等肥大基因的激活，增加心肌细胞表面积；过表达Nampt能够增加NF-κB依赖的转录活性，而沉默NF-κB的p65亚基能够部分取消Nampt对心肌细胞肥大的调控作用。结论过表达Nampt能够诱导心肌细胞肥大，其机制可能与NF-κB的激活有关。