丹酚酸A对心肌缺血再灌注损伤大鼠心率变异性和心肌损伤的影响
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摘要
目的观察丹酚酸A(salvianolic acid A,SAA)对心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MI/RI)大鼠心率变异性(HRV)和心肌损伤的影响。方法 SD大鼠60只,随机分为6组,即伪手术组、MI/RI模型组、SAA低,中,高(0.5 mg/kg,1 mg/kg和2 mg/kg)剂量组和阳性对照(2 mg/kg地尔硫艹卓)组,每组10只。采用结扎大鼠左冠状动脉前降支法,建立MI/RI大鼠模型,分别于结扎前给予相应药物。期间观察并分析心电图J点和HRV变化,同时再灌注结束后用伊文思蓝(evans blue,EB)和2,3,5-氯化三苯基四氮唑蓝(tetrazolium chloride,TTC)双重染色法测定心肌梗死面积,并测定血浆谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶(CK)及其同工酶(CK-MB)、超氧化物歧化酶(SOD)、丙二醛(MDA)和一氧化氮(NO)含量。结果与MI/RI模型组比,SAA低、中、高剂量组和地尔硫艹卓组均能显著降低再灌注期大鼠!-J值和J点平均值(P<0.05,P<0.01),减少心肌梗死面积和抑制AST、CK-MB和CK活性的升高(P<0.05,P<0.01);显著升高RR间期的标准差(SDNN)、相邻RR间期差值平方和的均方根(RMSSD)、HRV三角函数(tr.Ind)和高频(HFnu),并降低低频(LFnu)和LF/HF比值(P<0.05,P<0.01),还能显著升高NO含量和降低MDA含量(P<0.05)。结论丹酚酸可增加HRV,减少心肌梗死面积,其作用机制与丹酚酸A的抗氧化作用有关。
Objective To observe the effects of Salvianolic acid A( SAA) on heart rate variability( HRV) and myocardial injury in myocardial ischemia reperfusion injured( MI / RI) rats. Methods Sixty SD rats were divided into 6groups randomly( n = 10); the sham group,the MI / RI model group,high,middle and low-dose SAA group( 2 mg / kg,1 mg / kg and 0. 5 mg / kg) and positive control group( 2 mg / kg Diltiazem). The MI / RI model was made by ligating the left anterior descending branch of coronary artery in rats. Before ligation,the rats were intravenously administered with corresponding drugs. The changes of electrocardiogram of J point and HRV parameters were analyzed. At the end of reperfusion,the myocardial infarct size was measured by using Evans blue and tetrazolium chloride( TTC) double staining.The changes of plasma aspartate aminotransferase( AST),lactate dehydrogenase( LDH),creatine kinase( CK) and its isoenzyme( CK-MB),superoxide dismutase( SOD),malondialdehyde( MDA) and nitric oxide( no) content were also detected. Results Compared with MI / RI model group,SAA low,middle and high dose group and Diltiazem group were significantly reduced the total or average value of J point during reperfusion( P < 0. 05,P < 0. 01),reduced myocardial infarct size and inhibited the rising of AST,CK-MB and CK activities( P < 0. 05,P < 0. 01),and increased the standard deviation of RR intervals( SDNN),the root-mean-square of successive differences( RMSSD),HRV triangle index( tr.Ind) and high frequency( HFnu),reduced the low frequency( LFnu) and the ratio of LF / HF( P < 0. 05,P < 0. 01).Moreover,SAA could significantly increase the content of NO and reduce the content of MDA( P < 0. 05). Conclusion SAA could increase HRV and reduce myocardial infarction area in MI / RI rats,its mechanism of action maybe related with antioxidant effects.
Objective To observe the effects of Salvianolic acid A( SAA) on heart rate variability( HRV) and myocardial injury in myocardial ischemia reperfusion injured( MI / RI) rats. Methods Sixty SD rats were divided into 6groups randomly( n = 10); the sham group,the MI / RI model group,high,middle and low-dose SAA group( 2 mg / kg,1 mg / kg and 0. 5 mg / kg) and positive control group( 2 mg / kg Diltiazem). The MI / RI model was made by ligating the left anterior descending branch of coronary artery in rats. Before ligation,the rats were intravenously administered with corresponding drugs. The changes of electrocardiogram of J point and HRV parameters were analyzed. At the end of reperfusion,the myocardial infarct size was measured by using Evans blue and tetrazolium chloride( TTC) double staining.The changes of plasma aspartate aminotransferase( AST),lactate dehydrogenase( LDH),creatine kinase( CK) and its isoenzyme( CK-MB),superoxide dismutase( SOD),malondialdehyde( MDA) and nitric oxide( no) content were also detected. Results Compared with MI / RI model group,SAA low,middle and high dose group and Diltiazem group were significantly reduced the total or average value of J point during reperfusion( P < 0. 05,P < 0. 01),reduced myocardial infarct size and inhibited the rising of AST,CK-MB and CK activities( P < 0. 05,P < 0. 01),and increased the standard deviation of RR intervals( SDNN),the root-mean-square of successive differences( RMSSD),HRV triangle index( tr.Ind) and high frequency( HFnu),reduced the low frequency( LFnu) and the ratio of LF / HF( P < 0. 05,P < 0. 01).Moreover,SAA could significantly increase the content of NO and reduce the content of MDA( P < 0. 05). Conclusion SAA could increase HRV and reduce myocardial infarction area in MI / RI rats,its mechanism of action maybe related with antioxidant effects.
引文
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[11]吴茂红,吕玲.糖耐量异常对冠心病患者氧化应激和血管内皮功能、心率变异性的影响及阿卡波糖的干预作用[J].中国动脉硬化杂志,2014,22(3):287-292.
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[13]刘三运,王建明,朱志扬,等.通痹舒心颗粒对ACS伴焦虑抑郁病人hs-CRP、NT-pro BNP及心率变异性的影响[J].中西医结合心脑血管病杂志,2016,14(2):124-128.
[14]Huang J,Qin Y,Liu B,et al.In silico analysis and experimental validation of molecular mechanisms of salvianolic acid A-inhibited LPS-stimulated inflammation,in RAW264.7macrophages[J].Cell Prolif.2013,46(5):595-605.
[15]杨秀颖,强桂芬,张莉,等.丹酚酸A对缺血/再灌注心肌的保护作用研究[J].中国药理学通报,2011,27(8):1072-1076.
[2]Zhang J,He S,Wang X,et al.Effect of trimetazidine on heart rate variability in elderly patients with acute coronary syndrome[J].Pak J Med Sci,2016,32(1):75-78.
[3]张莉,张维库,赵莹,等.丹酚酸A的研究与进展[J].中国中药杂志,2011,36(9):2603-2609.
[4]Xu T,Wu X,Chen Q,et al.The anti-apoptotic and cardioprotective effects of salvianolic acid a on rat cardiomyocytes followingischemia/reperfusion by DUSP-mediated regulation of the ERK1/2/JNK pathway[J].PLo SOne,2014,9(7):e102292.
[5]Fan H,Yang L,Fu F,et al.Cardioprotective effects of salvianolic Acid a on myocardial ischemia-reperfusion injury in vivo and in vitro[J].Evid Based Complement Alternat Med,2012,2012:508938.
[6]潘永明,刘瑞敏,吴蔚,等.心率变异性分析评估不同因素致亚健康大鼠自主神经功能的影响[J].实验动物与比较医学,2012,32(6):467-472.
[7]杨涛涛,肖颖,奚赛飞,等.大鼠心肌梗死模型构建和评价方法的改良[J].中国比较医学杂志,2014,24(2):46-51.
[8]张旭东,蒋伟哲,焦杨,等.玉郎伞黄酮对大鼠心肌缺血再灌注损伤的保护作用[J].中国新药与临床杂志.2008,27(6):412-415.
[9]Quan W,Yin Y,Xi M,et al.Antioxidant properties of magnesium lithospermate B contribute to the cardioprotection against myocardial ischemia/reperfusion injury in vivo and in vitro[J].J Tradit Chin Med,2013,33(1):85-91.
[10]邵莹,吴启南,周婧,等.淡竹叶黄酮对大鼠心肌缺血/再灌注损伤的保护作用[J].中国药理学通报,2013,29(2):241-247.
[11]吴茂红,吕玲.糖耐量异常对冠心病患者氧化应激和血管内皮功能、心率变异性的影响及阿卡波糖的干预作用[J].中国动脉硬化杂志,2014,22(3):287-292.
[12]王燕琴,初而复,李欣,等.注射用苦参碱对阿霉素致大鼠心脏重构的影响[J].药物评价研究,2016,39(2):193-197.
[13]刘三运,王建明,朱志扬,等.通痹舒心颗粒对ACS伴焦虑抑郁病人hs-CRP、NT-pro BNP及心率变异性的影响[J].中西医结合心脑血管病杂志,2016,14(2):124-128.
[14]Huang J,Qin Y,Liu B,et al.In silico analysis and experimental validation of molecular mechanisms of salvianolic acid A-inhibited LPS-stimulated inflammation,in RAW264.7macrophages[J].Cell Prolif.2013,46(5):595-605.
[15]杨秀颖,强桂芬,张莉,等.丹酚酸A对缺血/再灌注心肌的保护作用研究[J].中国药理学通报,2011,27(8):1072-1076.