EGCG预防老年小鼠心脏肌钙蛋白Ⅰ表达下降及其机制研究
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Prevention of epigallocatechin gallate on decreasing expression of cardiac troponin-Ⅰ in aging mice hearts and its mechanism
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    摘要:

    重庆医科大学附属儿童医院心脏内科、儿童发育疾病研究教育部重点实验室、儿童发育重大疾病国家国际科技合作基地、儿科学重庆市重点实验室,重庆 400014

    Abstract:

    Objective:To investigate whether epigallocatechin gallate(EGCG) could prevent the declining expression of cardiac tro-ponin Ⅰ(cTnⅠ) in aging mice hearts and to study its mechanism. Methods:Expression levels of cTnⅠ mRNA and protein were de-tected by using RT-PCR and Western blot assays in each age group(n=5). A total of 32 C57 BL/6 female mice of 12 month old were randomly divided into the blank group,the EGCG low-dose group[EGCG-L,50 mg/(kg·d)],the EGCG medium-dose group[EGCG-M,100 mg/(kg·d)] and the EGCG high-dose group[EGCG-H,200 mg/(kg·d)]. Mice from EGCG intervention groups were treated with EGCG by water for 6 months. The female mice at age of 3-month were chosen as the young group(n=8). The cTnⅠ and HDAC1 mRNA expression were measured by RT-PCR. The protein level of cTnⅠ was determined by Western blot. The binding level of acetylated lysine 9 on histone H3(AcH3K9),HDAC1,transcription factors GATA4 and Mef2c near cTnⅠ’s promoter was identified by CHIP-Q-PCR. Results:During the aging process,both expressive levels of cTnⅠ mRNA and protein of 16-month-old mice[(0.913±0.150),(0.683±0.133)] began decreasing(P=0.002,P=0.003) when compared with 12-month-old mice[(1.483±0.226),(1.127±0.074)]. After EGCG intervention,the HDAC1 expression and the binding level in cTnⅠ’s promoter region in the EGCG-H group[(0.801±0.037),(0.225±0.153)] were lower than those in the blank group[(1.924±0.117),(0.963±0.105)](P=0.000,P=0.000). AcH3K9 levels in cTnⅠ’s promoter region and binding levels of GATA4 and Mef2c were (0.392±0.138),(0.404±0.150),(0.347±0.093),respectively. In the EGCG-H group,AcH3K9 levels(0.723±0.208),GATA4(1.051±0.239) and Mef2c(1.129±0.187) binding levels in the proximal promoter region of cTnⅠ gene were increased(P=0.014,P=0.000,P=0.000). Expressive levels of cTnⅠ mRNA and protein in the EGCG-H group[(0.943±0.114),(1.034±0.058)] were higher than those in the blank group[(0.093±0.033),(0.619±0.179)](P=0.000,P=0.007). Conclusion:High dose EGCG can prevent the decline of cTnⅠ in aging mice by inhibiting HDAC1 and elevating AcH3K9.

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贾忠莉,全珺珺,潘博,刘玲娟,田杰. EGCG预防老年小鼠心脏肌钙蛋白Ⅰ表达下降及其机制研究[J].重庆医科大学学报,2018,(3):332-

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  • 在线发布日期: 2019-05-30
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