[1]陈仁山,肖惠珍,刘 宁,等.参芪扶正注射液抑制ERK1/2、GATA4信号通路改善小鼠心力衰竭实验研究[J].陕西中医,2022,(1):8-12.[doi:DOI:10.3969/j.issn.1000-7369.2022.01.002]
 CHEN Renshan,XIAO Huizhen,LIU Ning,et al.Effect of Shenqi Fuzheng injection on heart failure in mice by inhibiting ERK1/2,GATA4 signaling pathway[J].,2022,(1):8-12.[doi:DOI:10.3969/j.issn.1000-7369.2022.01.002]
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参芪扶正注射液抑制ERK1/2、GATA4信号通路改善小鼠心力衰竭实验研究
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2022年1期
页码:
8-12
栏目:
基础研究
出版日期:
2022-01-05

文章信息/Info

Title:
Effect of Shenqi Fuzheng injection on heart failure in mice by inhibiting ERK1/2,GATA4 signaling pathway
作者:
陈仁山肖惠珍刘 宁王 帅丘文军杨天化高忠良陈清辉
(广州市中西医结合医院,广东 广州 510800)
Author(s):
CHEN RenshanXIAO HuizhenLIU NingWANG ShuaiQIU WenjunYANG TianhuaGAO ZhongliangCHEN Qinghui
(Guangzhou Hospital of Integrated Chinese and Western Medicine,Guangzhou 510800,China)
关键词:
心力衰竭 参芪扶正注射液 信号通路 动物实验 胞外信号调节激酶 GATA结合蛋白4
Keywords:
Heart failure Shenqi Fuzheng injection Signaling pathway Animal testing ERK GATA4
分类号:
R 541.61
DOI:
DOI:10.3969/j.issn.1000-7369.2022.01.002
文献标志码:
A
摘要:
目的:探讨参芪扶正注射液(SQ)治疗小鼠心力衰竭的疗效及机制。方法:将50只C57BL/6J小鼠随机分为正常组、模型组、阳性组、SQ低剂量组、SQ高剂量组,每组10只。异丙肾上腺素皮下注射诱导小鼠心力衰竭模型。SQ低剂量组和SQ高剂量组分别腹腔注射20、40 ml/kg参芪扶正注射液,阳性组给予80 mg/kg琥珀酸美托洛尔缓释片灌胃,正常组和模型组腹腔注射相应的0.9%氯化钠溶液。疗程14 d。观察治疗后小鼠左小室射血分数(LVEF)及左室短轴缩短率(LVFS),血清BNP浓度,心脏和肺脏脏器系数,心脏病理切片及心肌ERK1/2/GATA4信号通路的变化。结果:与正常组相比,模型组的LVEF和LVFS水平均有显著性降低,BNP浓度、心脏和肺脏脏器系数明显升高(P<0.05)。与模型组相比,阳性组、SQ低剂量组、SQ高剂量组的LVEF和LVFS水平均有显著性升高,BNP浓度、心脏和肺脏脏器系数明显下降(P<0.05),其中,SQ高剂量组LVEF、LVFS和BNP浓度改善优于SQ低剂量组(P<0.05)。病理切片显示,模型组心肌纤维化和炎症细胞浸润明显,阳性组、SQ低剂量组、SQ高剂量组心肌纤维大部分完整无炎症浸润。Western blot显示,模型组ERK1/2、p-ERK1/2、GATA4蛋白表达明显升高,阳性组、SQ低剂量组及SQ高剂量组ERK1/2、p-ERK1/2、GATA4蛋白表达明显减少(P<0.05)。结论:参芪扶正注射液可以改善心力衰竭小鼠的心脏收缩功能、减轻心肌纤维化,这种作用可能与抑制MAPK/ERK1/2/GATA4信号通路有关。
Abstract:
Objective:To investigate the therapeutic effect and mechanism of Shenqi Fuzheng injection(SQ)on heart failure in mice.Methods:Fifty C57BL/6J mice were randomly divided into normal group,model group,positive group,SQ low dose group and SQ high dose group,with 10 mice in each group.The heart failure model of mice was induced by subcutaneous injection of isoproterenol.The low-dose group and high-dose group were intraperitoneally injected with 20 ml/kg and 40 ml/kg Shenqi Fuzheng injection respectively.The positive group was intragastrically injected with 80 mg/kg metoprolol succinate sustained-release tablets.The normal group and model group were intraperitoneally injected with corresponding 0.9% normal saline.The course of treatment was 14 days.The changes of LVEF and LVFS,serum BNP concentration,heart and lung organ coefficient,cardiac pathological section and myocardial ERK1/2/GATA4 signaling pathway were observed after treatment.Results:Compared with the normal group,LVEF and LVFS levels of the model group were significantly decreased,BNP concentration,heart and lung organ coefficient were significantly increased(P<0.05).Compared with the model group,the levels of LVEF and LVFS in positive group,SQ low-dose group and SQ high-dose group were significantly increased,and the concentration of BNP,heart and lung organ coefficient were significantly decreased(P<0.05).The improvement of LVEF,LVFS and BNP in SQ high-dose group was better than that in SQ low-dose group(P<0.05).Pathological sections showed that myocardial fibrosis and inflammatory cell infiltration were obvious in the model group,and most of the myocardial fibers in the positive group,low-dose group and high-dose group were intact without inflammatory infiltration.Western blot showed that the protein expression of ERK1/2,p-ERK1/2 and GATA4 in the model group were significantly increased,while the protein expression of ERK1/2,p-ERK1/2 and GATA4 in the positive group,SQ low-dose group and SQ high-dose group was significantly decreased(P<0.05).Conclusion:Shenqi Fuzheng injection can improve cardiac systolic function and reduce myocardial fibrosis in mice with heart failure,which may be related to the inhibition of MAPK/ERK1/2/GATA4 signaling pathway.

参考文献/References:

[1] 中华医学会心血管病学分会心力衰竭学组.中国心力衰竭诊断和治疗指南2018[J].中华心力衰竭和心肌病杂志,2018,2(4):196-225.
[2] 于亚楠,杜玉颖,李 旭,等.心肌肥厚信号通路研究进展[J].现代生物医学进展,2018,18(4):779-782.
[3] 冠心病中临床研究联盟,中国中西医结合学会心血管疾病专业委员会,中华中医药学会心病分会.慢性心力衰竭中医诊疗专家共识[J].中医杂志,2014,55(14):1258-1260.
[4] 徐志强,张 雁,连 敏,等.参芪扶正注射液改善老年射血分数保留的心衰患者临床疗效机制初探[J].老年医学与保健,2020,26(4):537-541.
[5] 王俊萍,陈文璐.参芪扶正注射液治疗慢性心衰疗效及对患者BNP、CRP、MMP-9、TIMP-1水平的影响[J].陕西中医,2018,39(10):1366-1368.
[6] 中国心血管健康与疾病报告编写组.中国心血管健康与疾病报告2019概要[J].中国循环杂志,2020,35(9):833-854.
[7] 李倩晓,于 勤.心肌肥厚的信号转导机制的研究进展[J].医学综述,2011,17(13):1945-1948.
[8] 李彩红,王永刚,罗文平,等.中医药干预信号转导通路防治心力衰竭研究进展[J].中西医结合心脑血管病杂志,2015,13(15):1736-1739.
[9] 薛一涛,焦华琛,刘秀娟,等.心衰与Raf-MEK-ERK通路的关系及中医药研究进展[J].中国中医急症,2014,23(12):2250-2253.
[10] Qi JY,Tan YF,Fan DC,et al.Songling Xuemaikang capsule inhibits isoproterenol-induced cardiac hypertrophy via CaMKII and ERK1/2 pathways[J].Journal of Ethnopharmacology,2020,253:112660.
[11] Zhong L,Chiusa M,Cadar AG,et al.Targeted inhibition of ANKRD1 disrupts sarcomeric ERK-GATA4 signal transduction and abrogates phenylephrine-induced cardiomyocyte hypertrophy[J].Cardiovasc Res,2015,106(2):261-271.
[12] Jamieson W,Lara G,Mona N.From embryogenesis to adulthood:Critical role for GATA factors in heart development and function[J].IUBMB Life,2020,72(1):53-67.
[13] 李 昕,贾勇圣,郑建全.GATA4在心肌肥厚中的作用[J].医学与哲学,2008,29(1):48-49.
[14] 李 涛,周春燕.GATA-4在心肌基因表达调控中的作用及模式[J].国外医学:生理病理科学与临床分册,2005,25(3):244-246.
[15] Liang Q,De WL,Witt SA,et al.The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo[J].J Biol Chem,2001,276(32):30245-30253.
[16] 杨 萍,周玉平,夏 晴,等.HO-1介导黄芪甲苷抗原代心肌细胞缺氧/复氧损伤作用研究[J].天津中医药,2019,36(1):79-82.
[17] 陈广琴,何金龙,曲 楠,等.AMPK/p38 MAPK通路介导黄芪多糖抑制大鼠心肌肥厚的研究[J].广西医科大学学报,2020,37(6):1018-1023.
[18] 张 怡,靳晓飞,周晓红,等.黄芪甲苷调控自噬抑制缺氧缺糖/复氧复糖HT22细胞凋亡[J].中国药理学通报,2019,35(4):519-524.
[19] 朱天碧,张 钊,罗 飘,等.党参药理学作用的相关研究进展[J].神经药理学报,2018,8(6):46.
[20] 王 丹,张家美.参芪扶正注射液治疗慢性心力衰竭患者的研究进展[J].中西医结合心血管病杂志,2016,4(31):27-28,31.

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备注/Memo

备注/Memo:
基金项目:广东省中医药局科研项目(20191249)
更新日期/Last Update: 2022-01-09