黄芪对心肌梗死后大鼠心室重塑的改善作用及其对蛋白激酶C表达的影响

doi:10.13481/j.1671-587x.20150419

吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (04): 769-773.doi: 10.13481/j.1671-587x.20150419

黄芪对心肌梗死后大鼠心室重塑的改善作用及其对蛋白激酶C表达的影响

孙宇田¹, 刘聪聪², 徐萌², 王晶华², 高阳², 杨思睿², 周岩²

1. 吉林大学中日联谊医院药剂科, 吉林长春 130033;
2. 吉林大学第一医院儿科, 吉林长春 130021

收稿日期:2015-03-16 发布日期:2015-08-01
通讯作者: 周岩,副教授,硕士研究生导师(Tel:0431-88782556,E-mail:zhouyan0056@sina.com) E-mail:zhouyan0056@sina.com
作者简介:孙宇田(1971-),女,吉林省长春市人,主管药师,主要从事药物机理方面的研究。
基金资助:
吉林省科技厅重大项目资助课题(YYZX201260);吉林省发展改革委员会科研基金资助课题(2011007-13)

Improvement effects of Astragalus on ventricular remodeling in rat after myocardial infarction and its influence in expression of protein kinase C

SUN Yutian¹, LIU Congcong², XU Meng², WANG Jinghua², GAO Yang², YANG Sirui², ZHOU Yan²

1. Department of Pharmacy, China-Japan Union Hospital, Jilin Unversity, Changchun 130033, China;
2. Department of Pediatrics, First Hospital, Jilin University, Changchun 130021, China

Received:2015-03-16 Published:2015-08-01

摘要/Abstract

摘要：

目的: 观察黄芪(AS)注射液对心肌梗死后大鼠心室重塑的改善作用及对蛋白激酶C(PKC)的调节,阐明其作用机制。方法: 健康Wistar大鼠42只,采用结扎左冠状动脉前降支(LAD)的方法建立心肌梗死后心室重塑模型,将术后24 h存活的36只大鼠分为假手术组(生理盐水2 mL·d^-1腹腔注射)、模型组(生理盐水2 mL·d^-1腹腔注射)和黄芪治疗组(黄芪注射液6 g·d^-1,即2 mL·d^-1腹腔注射)。6周后观察各组大鼠的存活情况,超声心动图检测大鼠左室舒张期末径(LVEDD)、左室收缩期末径(LVESD)、左室射血分数(LVEF)和左室短轴缩短率(LVFS)。检测各组大鼠血浆脑利钠肽(BNP),Masson 染色测定心肌胶原容积分数(CVF),免疫组织化学染色和Western bloting法检测心肌细胞中PKCα和PKCε的表达水平。结果: 黄芪治疗组大鼠死亡数量少于模型组。与假手术组比较,模型组大鼠超声心动图指标LVEDD 和LVESD增加(P<0.05),LVEF和LVFS降低(P<0.05), 血浆BNP水平升高(P<0.05);与模型组比较,黄芪治疗组大鼠超声心动图指标LVEDD 和LVESD降低(P<0.05),LVEF和LVFS增加(P<0.05),血浆BNP水平降低(P<0.05)。与假手术组比较,模型组大鼠心肌CVF增加(P<0.05);与模型组比较,黄芪治疗组大鼠心肌CVF减少(P<0.05);与假手术组比较,模型组大鼠心肌细胞中PKCα表达水平明显增加(P<0.05);与模型组比较,大鼠心肌细胞中PKCα表达水平明显降低(P<0.05),PKCε表达水平明显增加(P<0.05)。结论: 黄芪注射液可以改善心肌梗死后大鼠的心室重塑,其机制可能通过上调PKCε、抑制PKCα表达而实现的。

关键词: 黄芪, 蛋白激酶C, 心室重塑

Abstract:

Objective To observe the improvement effect of Astragalus(AS) Injection on the ventricular remodeling in the rats after myocardial infarction and its regulation effect on the protein kinase C (PKC), and to clarify the mechanisms. Methods The left anterior descending(LAD) branch of coronary artery of 42 healthy Wistar rats were ligated in order to establish ventricular remodeling model after myocardial infarction.36 rats survived after 24 h were divided into three groups and 12 in each group. The rats in sham operation group were given physiological saline 2 mL·d^-1 by intraperitoneal injection; the rats in myocardial infarction group (model group) were given physiological saline 2 mL·d^-1 by intraperitoneal injection;the rats in AS group were treated with AS Injection 6 g·d^-1 (2 mL·d^-1) by intraperitoneal injection.After 6 weeks the survival situation of the rats in various groups was observed.The echocardiographic examination was made to inspect the left ventricular end diastolic diameter (LVEDD),left ventricular end systolic diameter (LVESD),left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS).The levels of plasma brain natriuretic peptide (BNP) of the rats in various groups were detected.Masson staining was used to determine the collagen volume fraction (CVF) of myocardium and the PKCα and PKCε expression levels in myocardial cells were detected by immunohistochemical staining and Western blotting method. Results The number of dad rats in AS group was less than that in model group.Compared with sham operation group,the LVESD and LVEDD of the rats in model group were increased (P<0.05),the LVEF and LVFS were decreased (P<0.05),and the BNP lelvel was increased (P<0.05). Compared with model group,the LVESD and LVEDD of the rats in AS group were decreased (P<0.05),the LVEF and LVFS were increased (P<0.05),and the BNP level was decreased (P<0.05).Compared with sham operation group,the CVF in the myocardial cells of the rats in model group was increased(P<0.05). Compared with model group,the CVF in the myocardial cells of the rats in AS group was decreased (P<0.05). Compared with sham operation group,the PKC expression level in the myocardial cells of the rats in model group was increased significantly (P<0.05). Compared with model group,the PKCα expression level in the myocardial cells of the rats in AS group was decreased significantly (P<0.05),and the PKCε expression level was increased significantly (P<0.05). Conclusion AS Injection can improve the ventricular remodeling in the rats after myocardial infarction,and its mechanism may be related to up-regulating the expression of PKCε and inhibiting the expression of PKCα.

Key words: Astragalus, protein kinase C, ventricular remodeling

中图分类号:

R285.5

孙宇田, 刘聪聪, 徐萌, 王晶华, 高阳, 杨思睿, 周岩. 黄芪对心肌梗死后大鼠心室重塑的改善作用及其对蛋白激酶C表达的影响[J]. 吉林大学学报(医学版), 2015, 41(04): 769-773.

SUN Yutian, LIU Congcong, XU Meng, WANG Jinghua, GAO Yang, YANG Sirui, ZHOU Yan. Improvement effects of Astragalus on ventricular remodeling in rat after myocardial infarction and its influence in expression of protein kinase C[J]. Journal of Jilin University Medicine Edition, 2015, 41(04): 769-773.

参考文献

[1] Jin M,Zhao K,Huang Q,et al.Structural features and biological activities of the polysaccharides from Astragalus membranaceus[J].Int J Biol Macromol,2014,64(3):257-266.

[2] Zeng L,Webster SV,Newton PM.The biology of protein kinase C[J].Adv Exp Med Biol,2012,740(2):639-661.

[3] Wang LY,Yang SJ.The function of protein kinase C in myocardial fibrosis[J].Yao Xue Xue Bao,2010,45(12):1467-1471.

[4] Burchfield JS,Xie M,Hill JA.Pathological ventricular remodeling:mechanisms:part 1 of 2[J].Circulation,2013,128(4):388-400.

[5] Acquatella H.Echocardiography in Chagas heart disease[J].Circulation,2007,115(9):1124-1131.

[6] Fayssoil AI,Tournoux F.Analyzing left ventricular function in mice with Doppler echocardiography[J].Heart Fail Rev,2013,18(4):511-516.

[7] Troughton RW,Richards AM.BNP for clinical monitoring of heart failure[J].Heart Fail Clin,2006,2(3):333-343.

[8] Yang QY,Chen KJ,Lu S,et al.Research progress on mechanism of action of Radix Astragalus in the treatment of heart failure[J].Chin J Integr Med,2012,18(3):235-240.

[9] Li R,Zhang Q,Yi QJ.Effect of carvedilol and Radix astragali on ryanodine receptor in heart failure in mice[J].Zhonghua Er Ke Za Zhi,2011,49(6):433-438.

[10] Fu S,Zhang J,Menniti-Ippolito F,et al.Huangqi injection (a traditional Chinese patent medicine) for chronic heart failure:a systematic review[J].PLoS One,2011,6(5):e19604.

[11] Dai H,Jia G,Liu X,et al.Astragalus polysaccharide inhibits isoprenaline-induced cardiac hypertrophy via suppressing Ca²⁺-mediated calcineurin/NFATc3 and CaMKⅡ signaling cascades[J].Environ Toxicol Pharmacol,2014,38(1):263-271.

[12] 关凤英,李红,杨世杰.黄芪甲苷通过诱导NO生成并激活PKCε对大鼠心肌缺血再灌损伤的保护研究[J].吉林大学学报:医学版,2010,36(2):340-343.

[13] Ma X,Zhang K,Li H,et al.Extracts from Astragalus membranaceus limit myocardial cell death and improve cardiac function in a rat model of myocardial ischemia[J].J Ethnopharmacol,2013,149(3):720-728.

[14] Malhotra A,Kang Bp,Opaumi D,et al.Molecular biology of protein kinase C aignaling in cardiac myocytes[J].Mol Cell Biochem,2001,225(1):97-107.

[15] Zeng L,Webster SV,Newton PM.The biology of protein kinase C[J].Adv Exp Med Biol,2012,740(2):639-661.

[16] 余志斌,王云英,张然,等.心肌肥厚过程中PKC的双刃剑作用[J].生理科学进展,2007,38(4):339-342.

[17] Mochly-Rosen D,Das K,Grimes KV.Protein kinase C,an elusive therapeutic target? [J].Nat Rev Drug Discov,2012,11(12):937-957.

[18] Song X,Qian X,Shen M,et al.Protein kinase C promotes cardiac fibrosis and heart failure by modulating galectin-3 expression[J].Biochim Biophys Acta,2015,1853(2):513-521.

黄芪对心肌梗死后大鼠心室重塑的改善作用及其对蛋白激酶C表达的影响

Improvement effects of Astragalus on ventricular remodeling in rat after myocardial infarction and its influence in expression of protein kinase C

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