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谢益文,徐素美,陈芝芸,杨晴柔,何蓓晖.非酒精性脂肪性肝病进展中肝组织细胞衰老相关基因P21、SIRT6和NF-κB表达的变化[J].浙江中西医结合杂志,2020,30(8):
非酒精性脂肪性肝病进展中肝组织细胞衰老相关基因P21、SIRT6和NF-κB表达的变化
Changes in the expression of hepatocyte senescence related genes P21, SIRT6 and NF-κB in the progression of non-alcoholic fatty liver disease
投稿时间:2019-12-24  修订日期:2020-06-01
DOI:
中文关键词:  小鼠;非酒精性脂肪性肝病  肝细胞衰老;P21;SIRT6/NF-κB
英文关键词:Mice  Nonalcoholic fatty liver disease  Hepatocyte senescence  P21  SIRT6/NF-κB
基金项目:浙江省医药卫生科研项目:基于SIRT6/NF-κB通路探讨非酒精性脂肪性肝病小鼠肝细胞衰老机制,编号:2019RC057
作者单位E-mail
谢益文 浙江中医药大学附属第一医院 892245585@qq.com 
徐素美* 浙江中医药大学附属第一医院 927703128@qq.com 
陈芝芸 浙江中医药大学附属第一医院  
杨晴柔 浙江中医药大学  
何蓓晖 浙江中医药大学附属第一医院  
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中文摘要:
      目的:探讨非酒精性脂肪性肝病进展中肝组织细胞衰老相关基因P21、SIRT6和NF-κB表达的变化情况。方法:采用高脂饮食建立 NAFLD 小鼠模型,分别在喂养第8 周、16周、24 周 3 个时相点, RealTime-PCR动态检测肝组织P21、SIRT6和NF-κB mRNA , 研究肝组织细胞衰老相关基因P21、SIRT6和NF-κB表达的变化。结果: RealTime-PCR结果显示,P21 mRNA表达水平在模型8周组与正常8周组差异无统计学意义[(1.38±0.70)比(1.10±0.51),P>0.05],而在模型16周组和24周组则较同期正常组显著增高[(2.04±0.94)比(1.17±0.59),P<0.05;(1.83±0.64)比(1.04±0.31),P<0.01];SIRT6 mRNA表达水平在模型8周组较正常8周组明显增高[(1.82±0.50)比(1.14±0.67),P<0.05],而模型16周组较正常16周组有下降趋势,但差异无统计学意义[(0.88±0.43)比(1.27±1.03),P>0.05],模型24周组则较正常24周组明显下降[(0.56±0.18)比(1.14±0.65),P<0.05];NF-κB mRNA随造模时间(8周、16周、24周)增加而稍有增强,但与同期正常组相比差异均无统计学意义[(1.08±0.64)、(1.21±0.24)、(1.44±0.67)比(1.06±0.37)、(0.95±0.42)、(1.08±0.43),P均>0.05]。结论:随NAFLD进展,肝细胞衰老现象逐渐增多,SIRT6在疾病进展中出现特征性的先升高后降低趋势,SIRT6基因在肝细胞衰老过程中起着重要作用。阻遏肝细胞衰老,可能成为NAFLD治疗的潜在靶点。
英文摘要:
      Objective: To investigate the changes in the expression of hepatocyte senescence related genes P21, SIRT6 and NF-κB in the progression of non-alcoholic fatty liver disease. Methods: A NAFLD mouse model was established using a high-fat diet. P21, SIRT6 and NF-κB mRNA in liver tissues were dynamically detected by RealTime-PCR at 3 points of week 8, week 16 and week 24, respectively, to study the changes in the expression of hepatocyte senescence related genes P21, SIRT6 and NF-κB. Results: RealTime-PCR results showed that there was no significant difference in P21 mRNA expression between the 8-week model group and the 8-week normal group [(1.38 ± 0.70) ratio (1.10 ± 0.51), P> 0.05]. In the 16-week or 24-week model group, it was significantly higher than the normal group in the same period [(2.04 ± 0.94) ratio (1.17 ± 0.59), P <0.05; (1.83 ± 0.64) ratio (1.04 ± 0.31), P <0.01]. The expression level of SIRT6 mRNA in the 8-week model group was significantly higher than the 8-week normal group [(1.82 ± 0.50) ratio (1.14 ± 0.67), P <0.05], while the 16-week model group had a downward trend compared with the 16-week normal group, but the difference was not statistically significant [(0.88 ± 0.43) ratio (1.27 ± 1.03), P> 0.05]. In addition, the 24-week model group was significantly lower than the normal 24-week group [(0.56 ± 0.18) ratio (1.14 ± 0.65), P <0.05]. NF-κB mRNA increased slightly with the increase of modeling time (8 weeks, 16 weeks, 24 weeks), but there was no significant difference compared with the normal group during the same period [(1.08 ± 0.64), (1.21 ± 0.24), (1.44 ± 0.67) ratio (1.06 ± 0.37), (0.95 ± 0.42), (1.08 ± 0.43), all P> 0.05]. Conclusion: With the progress of NAFLD, the phenomenon of hepatocyte senescence gradually increases, and SIRT6 typically increases and then decreases in disease progression. SIRT6 gene plays an important role in the aging process of liver cells. Inhibition of hepatocyte senescence may be a potential target for the treatment of NAFLD.
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