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组蛋白去乙酰化酶1在小鼠非酒精性脂肪肝中的表达和作用[J]. 中山大学学报(医学科学版), 2016,37(6).
Role of Histone Deacetylase 1 in Course of Mice NAFLD[J]. Journal of Sun Yat-sen University (Medical Sciences), 2016, 37(6).
【目的】探讨组蛋白去乙酰化酶1(HDAC1)在小鼠非酒精性脂肪肝病程中肝组织的表达和作用,研究其中的可能机制。【方法】分别给予C57BL/6小鼠素食和高脂饮食9周,用western blot检测肝脏组织HDAC1、HDAC3和胆固醇调节元件结合蛋白(SREBP)的表达;培养肝癌HepG2细胞,油酸处理细胞,对细胞进行油红染色并用western blot检测处理后HDAC1、HDAC3和SREBP的表达;用HDAC1抑制剂预处理HepG2细胞,再用油酸处理,western blot检测HDAC1、HDAC3和SREBP的表达。【结果】高脂饮食饲养小鼠9周时,可见肝脏呈明显的脂肪肝表现,与素食小鼠肝组织相比,HDAC1和SREBP的蛋白表达明显升高(n=8,均P<0.05),而HDAC3的变化不明显(P>0.05),HDAC1的蛋白表达与高脂饮食时间呈正相关(r=0.941,P<0.05)。油酸处理HepG2细胞后,与对照组细胞相比,油红染色可见细胞大量脂肪颗粒聚集,伴有HDAC1和SREBP蛋白表达升高(n=6, P<0.05),HDAC3表达变化不明显。HDAC1抑制剂预处理HepG2细胞后,与未预处理细胞相比,SREBP的蛋白表达明显受到抑制。【结论】HDAC1而非HDAC3参与了脂肪肝的进程,可能在蛋白水平通过促进SREBP的转录和表达对脂肪肝起到促进作用。
【Objective】 To investigate histone deacetylase 1 (HDCA1) expression in liver tissue of mice in the course of nonalcoholic fatty liver disease (NAFLD) and its correlation with sterol-regulatory element binding protein (SREBP)
and further study the possible mechanism. 【Method】 C57BL/6 mice were fed with chow diet and high fat diet (HFD) for 9 weeks. Expressions of HDAC1
HDAC3 and SREBP in liver tissue of mice were detected by western blot. HepG2 cells were stained by oil red after the cells were treated with oleic acid for 24h
and HDAC1
HDAC3 and SREBP expressions in HepG2 cells were detected by western blot. Furthermore
HepG2 cells were pretreated with HDAC1 inhibitor and then treated with oleic acid
HDAC1
HDAC3 and SREBP expressions in HepG2 cells were detected by western blot. 【Results】The liver of mice appeared obvious steatosis on 9th week of HFD. Compare with the liver tissue of mice fed with chow diet
the expressions of HDAC1 and SERBP protein were statistically increased in the liver tissue of mice fed with HFD for 9 weeks (n=8
all P<0.05)
but HDAC3 appeared no difference. The protein expression of HDAC1 in mice liver was positively correlated with the duration of HFD (r=0.941
P<0.05). Accompany with a large amount of fat granules accumulating in HepG2 cell stained by oil red after treated with oleic acid for 24h
the protein expressions of HDAC1 and SREBP in HepG2 cells were dramatically increased compare with those of cells without oleic acid treatment (n=6
P<0.05)
and HDAC3 had no change. After HepG2 cells were pretreated with HDAC1 inhibitor
the elevated of SREBP protein induced by oleic acid was obviously inhibited. 【Conclusion】 It is HDAC1
but not HDAC3 play an important role in the course of NAFLD
which could at protein level accelerate the formation of NAFLD through inducing the SREBP protein expression.
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