摘要
目的:探讨乙醇对心肌祖细胞毒性作用的表观遗传机制。方法:以心肌祖细胞株为研究对象,用200mmol/L乙醇和溶解于该浓度乙醇的不同浓度姜黄素(5μmol/L,15μmol/L,25μmol/L)处理。Western blot检测组蛋白H3K9乙酰化水平,筛选出姜黄素的有效干预浓度,实时定量PCR检测心脏发育相关基因GATA4,Mef2c,Tbx5mRNA表达量的变化。结果:200mmol/L乙醇使组蛋白H3K9乙酰化水平升高2.76倍(P<0.05),同时使心脏发育相关基因GATA4,Mef2c,Tbx5表达均增加,其中GATA4,Mef2c较对照组有统计学差异(P<0.05)。5μmol/L、15μmol/L姜黄素分别使组蛋白H3K9乙酰化水平升高2.22、1.58倍(P<0.05);25μmol/L姜黄素使组蛋白H3K9乙酰化水平降至对照组水平,同时使心脏发育相关基因GATA4,Mef2c,Tbx5表达较乙醇组均下降,且与对照组无差异(P>0.05)。结论:姜黄素可干预乙醇对心肌祖细胞的高乙酰化失衡以及进而发生的相关基因的表达异常,可为了解乙醇致畸的机制以及临床预防先天性心脏病提供新的思路。
Objective：To investigate the cytotoxicity inducesd by alcohol and its epigenetic mechanism in the cardiac progenitor cells.Method：Cardiac progenitor cells were treated with alcohol at 200 mmol/L and curcumin at 5,15,25 μmol/L that dissolved in the alcohol.Western blot analysis was used to detect the acetylation of histone H3K9,select the effective concentration of curcumin;and real-time PCR was used to measure the expressions of heart development-related genes GATA4,Mef2c and Tbx5.Result：Alcohol at 200 mmol/L increased the acetylation of H3K9 by 2.76-fold（P0.05）,and increased the expression of heart development-related genes GATA4,Mef2c and Tbx5.There was significant difference in GATA4 and Mef2c compared with control group（P0.05）.Curcumin at 5,15 μmol/L increased the acetylation of H3K9 by 2.22-and 1.58-fold respectively（P0.05）;curcumin at 25 μmol/L decreased the acetylation of H3K9 to the level of control group,and decreased the expression of heart development-related genes GATA4,Mef2c and Tbx5 to the level of control group（P0.05）.Conclusion：Curcumin can intervene the H3K9 acetylation increasing and anomalous expression of heart development-related genes that induced by alcohol in the cardiac progenitor cells.It may play a role in the pathogenesis of alcohol induced congenital heart diseases.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2011年第4期303-306,共4页
Journal of Clinical Cardiology
基金
973基金资助(No:2010CB529505)
国家自然科学基金资助(No:30770889)
