益母草碱对异丙肾上腺素诱导大鼠心肌重构的影响

袁露; 梁博志; 罗建华; 卢丽娜; 杨辉; 李利; 杨冬花

益母草碱对异丙肾上腺素诱导大鼠心肌重构的影响

1.
贵州省人民医院干医科，贵州贵阳 550002
2.
贵阳中医学院第二附属医院，贵州贵阳 550003
3.
贵州省人民医院内分泌科，贵州贵阳 550002

计量
- 文章访问数: 753
- HTML全文浏览量: 5
- PDF下载量: 544
- 被引次数: 0
出版历程
- 刊出日期: 2019-03-10

Effect and Mechanism of Leonurine on Rats with Ventricular Remodeling Induced by Isoproterenol

1.
Department of Medicine for Cadre, The People's Hospital of Guizhou Province, Guiyang, 550002, China
2.
The Second Affiliated Hospital of Guiyang TCM College, Guiyang, 550003, China
3.
Department of Endocrinology, The People's Hospital of Guizhou Province, Guiyang, 550002, China

摘要

摘要: 目的观察益母草碱对异丙肾上腺素（ISO）诱导大鼠心肌重构的影响，并探讨可能涉及的机制。方法 10只SD大鼠作正常对照组；另80只SD大鼠作为实验鼠，连续2周腹腔注射ISO诱导心肌重构动物模型。造模成功后将实验鼠随机分为5组:模型组，益母草碱低（7.5 mg/(kg·d)）、中（15 mg/(kg·d)）、高（30 mg/(kg·d)）剂量组以及p38丝裂原活化蛋白激酶（p38MAPK）抑制剂组（0.3 mg/(kg·d)），予相应药物腹腔注射2周后，HE染色观察左心室肌组织形态学变化；免疫组织化学法观察左心室肌组织转化生长因子-β1（TGF-β1)的表达；ELISA法及硝酸还原酶法检测血清内皮素（ET-1）和一氧化氮（NO）含量； qPCR 法检测左心室肌组织p38MAPK、肌细胞增强因子2（MEF2）、β-肌球蛋白重链（β-MHC）、α-肌球蛋白重链（α-MHC） mRNA的表达水平；Western blot法检测左心室肌组织ET-1、磷酸化p38MAPK（p-p38MAPK）和MEF2蛋白的表达水平。结果与模型组比较，高剂量益母草碱能明显改善大鼠心肌重构病理改变，减少TGF-β1的表达（P<0.05）；减少血清ET-1含量，升高NO含量（P<0.05）；下调p38MAPK、MEF2和β-MHC mRNA的表达水平及ET-1、p-p38MAPK和MEF2蛋白的表达水平，上调α-MHC mRNA的表达水平（P<0.05）。结论益母草碱有抑制ISO诱导的大鼠心肌重构的作用，其机制可能与抑制p38MAPK/MEF2信号通路有关。
- 益母草碱 /
- 心肌重构 /
- p38丝裂原活化蛋白激酶 /
- 肌细胞增强因子2
Abstract: OBJECTIVE To observe the effect of leonurine on rats with ventricular remodeling induced by isoproterenol(ISO) and to explore the possible mechanism involved. METHODS SD rats (n=10) were used as normal control group， and 80 rats were given ISO by intraperitoneal injection daily for 2 weeks to establish the model of ventricular remodeling. The model rats were divided into 5 groups randomly as model group， low-dose leonurine (7.5 mg/(kg·d)) group， middle-dose leonurine (15 mg/(kg·d)) group， high-dose leonurine (30 mg/(kg·d)) group and p38MAPK inhibitor (0.3 mg/(kg·d)) group. After the treatment for 2 weeks， the pathological change of left ventricular myocardial tissues was observed by HE staining，and the expression of TGF-β1 was determined by the method of immunohistochemistry. The serum concentrations of ET-1 and NO were measured by ELISA and nitrate reductase methods， respectively. The expression of p38MAPK， MEF2，β-MHC and α-MHC mRNA was detected by qPCR， and the protein expression of ET-1， p-p38MAPK and MEF2 was determined by Western blot. RESULTS Compared with model group， the pathological change of ventricular remodeling in high-dose leonurine group was attenuated， and the serum concentrations of NO and the mRNA expression of α-MHC in left ventricular myocardial tissues of high-dose leonurine group were higher (P<0.05).The expression of TGF-β1， the serum concentrations of ET-1， the mRNA expression of p38MAPK，MEF2 and β-MHC mRNA， and the protein expression of ET-1， p-p38MAPK and MEF2 were lower than those in model group (P<0.05). CONCLUSION Leonurine attenuates ventricular remodeling in the rats induced by ISO， and it is potentially associated with inhibiting p38MAPK/MEF2 signaling pathway.
- leonurine /
- ventricular remodeling /
- p38 mitogen-activated protein kinase /
- myocyte enhancer factor 2

HTML全文

参考文献(17)

[1]	AZEVEDO PS， POLEGATO BF， MINICUCCI MF， et al. Cardiac remodeling: Concepts， clinical impact， pathophysiological mechanisms and pharmacologic treatment[J]. Arq Bras Cardiol， 2016，106(1): 62-69.
[2]	ZHU YZ， WU W， ZHU Q， et al. Discovery of Leonuri and therapeutical applications: From bench to bedside[J].Pharmacol Ther， 2018， 188:26-35.
[3]	梁赵文，罗建华，杨冬花，等.益母草碱对慢性心力衰竭心肌重构大鼠心房利钠肽、血管紧张素Ⅱ影响的研究[J].贵州医药，2016，40（12）:1235-1238.
[4]	NGUYEN MN， KIRIAZIS H， GAO XM， et al. Cardiac fibrosis and arrhythmo-genesis[J].Compr Physiol， 2017， 7(3):1009-1049.
[5]	张勇涛，蒋凡.生理性和病理性心肌肥厚的信号传导机制[J].中华心血管病杂志，2015，43（3）：277-280.
[6]	MA Y， ZOU H， ZHU XX， et al. Transforming growth factor β: A potential biomarker and therapeutic target of ventricular remodeling[J]. Oncotarget， 2017，8(32): 53780-53790.
[7]	KONG P， CHRISTIA P， FRANGOGIANNIS NG.The pathogenesis of cardiac fibrosis[J].Cell Mol Life Sci， 2014，71(4):549-574.
[8]	宋冰，丁利.硫化氢抑制p38MAPK和NF-κB p65信号通路活性改善糖尿病心肌纤维化的作用和机制[J]. 解放军医学杂志，2016，41（11）：902-907.
[9]	ARABACILAR P， MARBER M. The case for inhibiting p38 mitogen-activated protein kinase in heart failure[J].Front Pharmacol， 2015， 6:102.
[10]	DAVENPORT AP， HYNDMAN KA， DHAUN N， et al. Endothelin[J]. Pharmacol Rev， 2016， 68(2): 357-418.
[11]	JEN HL， LIU PL， CHEN YH， et al. Peroxisome proliferator-activated receptorα reduces endothelin-1-caused cardiomyocyte hypertrophy by inhibiting nuclear factor-κB and adiponectin[J]. Mediators Inflamm， 2016， 2016: 5609121.
[12]	WENG X， YU L， LIANG P， et al. A crosstalk between chromatin remodeling and histone H3K4 methyltransferase complexes in endothelial cells regulates angiotensin Ⅱ-induced cardiac hypertrophy[J]. J Mol Cell Cardiol， 2015，82: 48-58.
[13]	GONG X， MING X， DENG P， et al. Mechanisms regulating the nuclear translocation of p38 MAP kinase[J]. J Cell Biochem， 2010，110(6):1420-1429.
[14]	CHEN X， GAO B， PONNUSAMY M， et al. MEF2 signaling and human diseases[J]. Oncotarget， 2017， 8(67):112152-112165.
[15]	ZHAO M， NEW L， KRAVCHENKO VV， et al. Regulation of the MEF2 family of transcription factors by p38[J]. Mol Cell Biol，1999，19(1):21-30.
[16]	HAN J， JIANG Y， LI Z， et al. Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation[J]. Nature，1997，386(6622):296-299.
[17]	DADSON K， TURDI S， HASHEMI S， et al. Adiponectin is required for cardiac MEF2 activation during pressure overload induced hypertrophy[J]. J Mol Cell Cardiol， 2015， 86:102-109.