参麦注射液对急性心肌梗死大鼠心肌纤维化的干预作用研究
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摘要
目的:研究参麦注射液(SMI)对急性心肌梗死(AMI,简称"心梗")模型大鼠心肌保护的作用机制。方法:采用左冠状动脉前降支结扎法复制心梗模型。造模成功后,给予相关药物每天一次,连续14 d。应用超声仪进行心功能及血流动力学分析,并结合苏木精-伊红染色及MASSON染色观察心肌形态学变化,利用逆转录聚合酶链式反应(RT-PCR)检测心肌纤维化因子基质金属蛋白酶-2(MMP-2)、转化生长因子-β(TGF-β)的表达水平。结果:AMI大鼠左心室射血分数(LVEF)、短轴缩短率(FS)、流出道血流峰值(AV Peak Velocity)、峰压(AV Peak Pressure)、均速(AoV VTI Mean Vel)和阶压(AoV VTI Mean Grad)均显著降低,心肌组织中MMP-2和TGF-β的信使RNA(mRNA)表达程度均明显升高。形态学结果显示,AMI大鼠心肌组织中心肌细胞少量残存,结构紊乱,纤维化程度高,心梗面积百分比显著升高。SMI可显著改善AMI大鼠LVEF、FS、流出道血流峰值、峰压、均速及阶压,下调心肌组织中MMP-2和TGF-β的mRNA表达水平。此外,SMI使心肌细胞坏死数量减少,纤维化程度减轻,心梗面积百分比下降。结论:SMI可通过改善心功能,抑制心肌纤维化,减轻心梗程度等方面发挥其抗AMI作用。
OBJECTIVE To study the mechanism of Shenmai injection(SMI) on myocardial protection in rats with acute myocardial infarction(AMI). METHODS Myocardial infarction model was established by ligation of left anterior descending coronary artery. After establishment of the model, the related drugs were administered once daily for 14 days. The cardiac function and hemodynamics were analyzed by echocardiography. The morphological changes of myocardium were observed by hematoxylin-eosin staining and MASSON staining. The expression levels of matrix metalloproteinase-2(MMP-2) and transforming growth factor-β(TGF-β) were detected by reverse transcription polymerase chain reaction(RT-PCR). RESULTS The LVEF, FS, AV Peak Velocity, AV Peak Pressure, AoV VTI Mean Vel and AoV VTI Mean Grad were significantly decreased in AMI rats, and messenger RNA(mRNA) expression of MMP-2 and TGF-β were significantly increased in myocardial tissue. The morphological analysis showed that there was little cardiomyocyte remained in myocardium with structural disorder and high degree of fibrosis. Meanwhile, the percentage of myocardial infarction area was significantly increased(P<0.05). SMI can reduce the level of LVEF, FS, AV Peak Velocity, AV Peak Pressure, AoV VTI Mean Vel and AoV VTI Mean Grad significantly(P<0.05) as well as downregulate the expression level of mRNA of MMP-2 and TGF-β(P<0.05). In addition, SMI reduced the number of myocardial cell necrosis, the degree of fibrosis, and the percentage of myocardial infarction area.(P<0.05). CONCLUSION SMI can improve cardiac function, inhibit myocardial fibrosis and reduce the degree of myocardial infarction.
OBJECTIVE To study the mechanism of Shenmai injection(SMI) on myocardial protection in rats with acute myocardial infarction(AMI). METHODS Myocardial infarction model was established by ligation of left anterior descending coronary artery. After establishment of the model, the related drugs were administered once daily for 14 days. The cardiac function and hemodynamics were analyzed by echocardiography. The morphological changes of myocardium were observed by hematoxylin-eosin staining and MASSON staining. The expression levels of matrix metalloproteinase-2(MMP-2) and transforming growth factor-β(TGF-β) were detected by reverse transcription polymerase chain reaction(RT-PCR). RESULTS The LVEF, FS, AV Peak Velocity, AV Peak Pressure, AoV VTI Mean Vel and AoV VTI Mean Grad were significantly decreased in AMI rats, and messenger RNA(mRNA) expression of MMP-2 and TGF-β were significantly increased in myocardial tissue. The morphological analysis showed that there was little cardiomyocyte remained in myocardium with structural disorder and high degree of fibrosis. Meanwhile, the percentage of myocardial infarction area was significantly increased(P<0.05). SMI can reduce the level of LVEF, FS, AV Peak Velocity, AV Peak Pressure, AoV VTI Mean Vel and AoV VTI Mean Grad significantly(P<0.05) as well as downregulate the expression level of mRNA of MMP-2 and TGF-β(P<0.05). In addition, SMI reduced the number of myocardial cell necrosis, the degree of fibrosis, and the percentage of myocardial infarction area.(P<0.05). CONCLUSION SMI can improve cardiac function, inhibit myocardial fibrosis and reduce the degree of myocardial infarction.
引文
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[3] Huang ZQ,Hu TH.Research advancement of pharmacological and clinical research for Shenmai injection[J].J Clin Med(临床医药文献杂志),2017,4(14):2762-2763.
[4] Danieis A,van Bilsen M,Goldschmeding R,et al.Connective tissue growth factor and cardiac fibrosis acta physiologica[J].Oxford England,2009,195:321-338.
[5] Wang XY,Huang XM,Yang WD,et al.Effects of antioxidant therapy on prevention and treatment of ventricular remodeling in patients with acute myocardial infarction[J].Chin Hosp Pharm J (中国医院药学杂志),2017,37(12):1182-1184,1188.
[6] Roth GA,Johnson C,Abajobir A,et al.Global,regional,and national burden of cardiovascular diseases for 10 causes,1990 to 2015[J].J Am Coll Cardiol,2017,70(1):1-25.
[7] Chen JH,Chen YP.Effect evaluation of transthoracic color Doppler echocardiography in the diagnosis of hyperacute myocardial infarction[J].China Prac Med(中国实用医药),2014,9(18):35-36.
[8] Mu CP,Li C,Liu YB,et al.Effects of hydrogen on cardiac hemodynamics in rabbits with ischema-reperfusion injury[J].Chin J Integr Med Cardio/Cerebrovasc Dis(中西医结合心脑血管病杂志),2017,15(18):2245-2247.
[9] Li JF,Wang H,Jia L,et al.The improvement effect of Danhong injection on the cardiac function and left ventricular remodeling in myocardial infarction rats[J].Chin Hosp Pharm J (中国医院药学杂志),2013,33(5):373-376.
[10] Di RM,Xu P,Yang ZZ,et al.Establishment of acute myocardial infarction and evaluation of left ventricular remodeling in mice model[J].Jiangsu Med J(江苏医药),2014,40(13):1498-1500.
[11] Liu MM,Li AL,Xiu RJ.Research progress on matrix metalloproteinases[J].Chin J Pathophysiol(中国病理生理杂志),2018,34(10):1914-1920.
[12] Guan HS,Wang H,Shangguan HJ,et al.Effect of omapatrilat on myocardium TNF-α、MMP-2 expression and ventricular remodeling after myocardial infarction in rats[J].Chin Hosp Pharm J (中国医院药学杂志),2006,26(5):545-548.
[13] Bujak M,Frangogiannis NG.The role of TGF-β signaling in myocardial infarction and cardiac remodeling[J].Cardiovasc Res,2007,74(2):184-195.
[14] Hu Z,Chen JR,Wei J,et al.Establishment and evaluation experimental study of acute myocardial infarction in rats[J].Tianjin J Tradit Chin Med(天津中医药),2016,33(2):90-95.
[15] Zhang LQ.Effects of valsartan on ventricular remodeling in rats after experimental myocardial infarction[D].Shenyang:China Medical University(中国医科大学),2005.
[16] Wen XJ,Chen YJ,Li JD,et al.Effects of Shenmai injection on ventricular remodeling after acute myocardial infarction in rats[J].J Hebei North University (Medical Edition)(河北北方学院学报(医学版)),2006,23(4):9-12.
[17] Li JD,Wen XJ,Chen YJ,et al.Effects of Shenmai injection on cardiac function and ventricular remodeling in acute myocardial infarction rats[J].Chin J Basic Med Tradit Chin Med(中国中医基础医学杂志),2007,13(6):422-424.