鹿茸多肽对阿霉素所致心肌损伤模型大鼠心肌特异性转录因子Nkx 2.5、GATA4、ATF-2和MEF-2C的影响
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摘要
目的观察鹿茸多肽对阿霉素所致心肌损伤模型大鼠心肌特异性转录因子Nkx 2.5、GATA4、ATF-2、MEF-2C表达的影响。方法 Wistar大鼠60只随机分为6组,每组10只。腹腔注射阿霉素建立心肌损伤大鼠模型,连续给药21d。末次给药结束后1h,PowerLab数据采集分析系统检测各组大鼠心率及心电图ST段变化,Elisa法检测各组大鼠血清中Nkx2.5、GATA4、ATF-2和MEF-2C含量,Western-blot检测各组大鼠心脏中Nkx2.5、GATA4、ATF-2和MEF-2C蛋白表达水平。结果鹿茸多肽可明显降低阿霉素所致心肌损伤大鼠模型的心率,ST段上调幅度明显降低,升高大鼠血清中Nkx 2.5、GATA4和MEF-2C含量及上调心脏中蛋白水平(P<0.05或P<0.01),ATF-2无明显变化(P>0.05)。结论鹿茸多肽可明显缓解阿霉素所致的大鼠心肌损伤,其作用机制可能与调节心肌特异性转录因子Nkx 2.5、GATA4、MEF-2C水平有关。
Objective To observe the effects of Velvet antler polypeptide on the expression of myocardial specific transcription factors Nkx 2.5, GATA4, ATF-2 and MEF-2 C in rats with myocardial injury induced by adramycin. Methods Sixty Wistar rats were randomly divided into 6 groups, 10 rats in each group. The rat model of myocardial injury was established by intraperitoneal injection of adramycin for 21 days. One hour after the last dose, PowerLab data acquisition and analysis system was used to detect the heart rate and ST segment changes of ECG in each group. Use Elisa to detect the contents of Nkx2.5, GATA4, ATF-2 and MEF-2 C in serum of each group. Use Western-blot to detect the levels of Nkx2.5, GATA4, ATF-2 and MEF-2 C proteins in the hearts of rats in each group were detected by blot.Results The Velvet antler polypeptide significantly reduced the heart rate of the rat model of myocardial injury induced by adramycin, and the ST-segment up-regulation was significantly decreased. The serum levels of Nkx 2.5, GATA4 and MEF-2 C were increased and the protein levels in the heart were up-regulated(P<0.05 or P<0.01), there was no significant change in ATF-2(P>0.05).Conclusion Velvet antler polypeptide can significantly alleviate myocardial injury induced by adramycin in rats, and its mechanism may be related to the regulation of myocardial specific transcription factors Nkx 2.5, GATA4 and MEF-2 C.
Objective To observe the effects of Velvet antler polypeptide on the expression of myocardial specific transcription factors Nkx 2.5, GATA4, ATF-2 and MEF-2 C in rats with myocardial injury induced by adramycin. Methods Sixty Wistar rats were randomly divided into 6 groups, 10 rats in each group. The rat model of myocardial injury was established by intraperitoneal injection of adramycin for 21 days. One hour after the last dose, PowerLab data acquisition and analysis system was used to detect the heart rate and ST segment changes of ECG in each group. Use Elisa to detect the contents of Nkx2.5, GATA4, ATF-2 and MEF-2 C in serum of each group. Use Western-blot to detect the levels of Nkx2.5, GATA4, ATF-2 and MEF-2 C proteins in the hearts of rats in each group were detected by blot.Results The Velvet antler polypeptide significantly reduced the heart rate of the rat model of myocardial injury induced by adramycin, and the ST-segment up-regulation was significantly decreased. The serum levels of Nkx 2.5, GATA4 and MEF-2 C were increased and the protein levels in the heart were up-regulated(P<0.05 or P<0.01), there was no significant change in ATF-2(P>0.05).Conclusion Velvet antler polypeptide can significantly alleviate myocardial injury induced by adramycin in rats, and its mechanism may be related to the regulation of myocardial specific transcription factors Nkx 2.5, GATA4 and MEF-2 C.
引文
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[3] 王姿谕,张明雪.温法在冠心病治疗中的应用[J].辽宁中医杂志,2016,43(3):654.
[4] 罗卫民,刘越峰,罗湘玉,等.金樱子对阿霉素诱导心肌损伤的保护作用及机制[J].中国生化药物杂志,2014,34(1):29.
[5] 冷雪,张立德,贾连群,等.人参皂苷Rb1对异丙肾上腺素诱导大鼠急性心肌缺血影响的作用机制[J].中国实验方剂学杂志,2015,21(24):104.
[6] 高玲,粟栗,杨婷,等.强心活力方对阿霉素引起心脏毒性的保护作用[J].中国实验方剂学杂志,2018,24(14):153.
[7] 马君,程阳阳,谭鹏,等.附子炮制品对阿霉素致急性心力衰竭的实验研究[J].时珍国医国药,2017,28(9):2136.
[8] 何怀阳,陈芳,黄琳,等.固本救心方对阿霉素致心力衰竭大鼠脑钠肽和睾酮的影响[J].时珍国医国药,2015,26(7):1631.
[9] 曲敬琨,张佳,张靖.蒽环类药物心脏毒性防治药物研究进展[J].中国肿瘤临床,2014,41 (22):1474.
[10] 张介宾.景岳全书[M].北京:人民卫生出版社,1992:548.
[11] 秦丹凤,侯平.温补心肾法治疗缓慢性心律失常简况[J].实用中医内科杂志,2016,30(6):109.
[12] Hisayuki H,Olson E N,Bassel-Duby R.Therapeutic approaches for cardiac regeneration and repair[J].Nat Rev Cardiol,2018,15(10):585.
[13] 黄晓巍,徐岩,韩冬,等.鹿茸多肽介导心肌干细胞分化对终末心肌分化基因ANP和MLC-2v表达的影响[J].吉林大学学报(医学版),2018,44(2):249.
[14] 王逸文,徐方剑,孙浩,等.鹿茸多肽提取工艺及其药理学作用[J].上海中医药杂志,2016,50(4):94.
[15] Zhang S S,Kim K H,Rosen A,et al.Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network[J].Proc Natl Acad Sci USA,2011,108(33):13576.
[16] 贺继刚,严丹,王平,等.GATA-4在心肌损伤修复中的作用机制研究进展[J].医学综述,2015,21(22):4033.