丹参川芎嗪对离体大鼠心肌缺血/再灌注损伤的保护作用
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摘要
目的通过对大鼠离体心脏灌流不同剂量受试药丹参川芎嗪(SLI),探讨受试药对离体心肌缺血/再灌注(I/R)损伤的保护作用。方法采用Langendorff离体心脏恒压灌流系统建立心肌缺血/再灌注模型。SD大鼠随机分为五组(n=11),包括空白对照组(Control)、模型组(Model)、SLI高剂量组(High)、中剂量组(Middle)、低剂量组(Low)。将分离后的大鼠心脏连接在Langendorff离体灌流仪器上,先平衡灌注20min,再全心停灌20min,然后复灌60min;空白对照组连续灌流100min。采用labchart生物信号采集仪器记录观察各受试药物组对心功能的影响。结果与模型组相比,SLI各剂量组I/R的相关指标LVDP、+dp/dtmax明显升高(P <0.05),冠脉流出液中LDH、CK、MDA含量显著降低(P <0.05),而SOD水平则明显升高。HE染色结果显示,模型组心肌细胞着色不均、纤维排列紊乱、心肌形态不完整,心肌纤维间可见中性粒细胞浸润,部分心肌细胞坏死,而SLI各剂量组均不同程度地改善了这一改变。结论 SLI能减轻离体心肌缺血/再灌注诱导的冠脉损伤,对心脏功能恢复具有促进作用,其机制可能与改善心肌舒缩功能,清除氧自由基有关。
Objective To investigate the protective effect of the drug on isolated cardiac ischemia/reperfusion(I/R)injury by salvia miltiorrhiza and ligustrazine injection(SLI) on isolated myocardial ischemia/reperfusion injury in rats. Methods Langendorff isolated cardiac constant pressure perfusion system was used to establish the myocardial ischemia/reperfusion model.SD rats were randomly divided into 5 groups(n=11),including control group,model group,SLI group,middle group and low group.The separated rat hearts were connected to the Langendorff isolated perfusion apparatus.The rat hearts were placed in equilibrium perfusion for 20 min,then completely stopped perfusion for 20 min,and then re-perfusion for 60 min.The blank control group was given continuous perfusion for 100 min.Labchart biological signal acquisition instrument was used to record and observe the effect of each drug group on cardiac function. Results Compared with the model group,the SLI dose groups had significantly higher I/R related indicators of LVDP and +dp/dtmax(P < 0.05).The contents of LDH,CK and MDA in coronary effluent were significantly decreased(P < 0.05),while the levels of SOD were significantly increased.The results of HE staining showed that the model group had uneven staining of myocardial cells,disorganized arrangement of fibers,and incomplete myocardial morphology,with neutrophil infiltration among myocardial fibers and necrosis of some myocardial cells,and the SLI dose groups improved this change to varying degrees. Conclusion SLI can alleviate isolated ischemia/reperfusion induced coronary artery injury and promote cardiac function recovery,and its mechanism may be related to improving myocardial systolic function and scavenging oxygen free radicals.
Objective To investigate the protective effect of the drug on isolated cardiac ischemia/reperfusion(I/R)injury by salvia miltiorrhiza and ligustrazine injection(SLI) on isolated myocardial ischemia/reperfusion injury in rats. Methods Langendorff isolated cardiac constant pressure perfusion system was used to establish the myocardial ischemia/reperfusion model.SD rats were randomly divided into 5 groups(n=11),including control group,model group,SLI group,middle group and low group.The separated rat hearts were connected to the Langendorff isolated perfusion apparatus.The rat hearts were placed in equilibrium perfusion for 20 min,then completely stopped perfusion for 20 min,and then re-perfusion for 60 min.The blank control group was given continuous perfusion for 100 min.Labchart biological signal acquisition instrument was used to record and observe the effect of each drug group on cardiac function. Results Compared with the model group,the SLI dose groups had significantly higher I/R related indicators of LVDP and +dp/dtmax(P < 0.05).The contents of LDH,CK and MDA in coronary effluent were significantly decreased(P < 0.05),while the levels of SOD were significantly increased.The results of HE staining showed that the model group had uneven staining of myocardial cells,disorganized arrangement of fibers,and incomplete myocardial morphology,with neutrophil infiltration among myocardial fibers and necrosis of some myocardial cells,and the SLI dose groups improved this change to varying degrees. Conclusion SLI can alleviate isolated ischemia/reperfusion induced coronary artery injury and promote cardiac function recovery,and its mechanism may be related to improving myocardial systolic function and scavenging oxygen free radicals.
引文
[1]赵亚玲,敖虎山.心肌缺血再灌注损伤的研究进展[J].中国循环杂志,2011,26(5):396-398.
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[3]贺常萍,张家兵.急性心肌梗死再灌注治疗的研究进展[J].医学综述,2018,25(12):2394-2400.
[4]Wong KL,Wu KC,Wu RS,et al.Tetramethylpyrazine inhibits angiotensin II-increased NAD(P)H oxidase activity and subsequent proliferation in rat aortic smooth muscle cells[J].Am J Chin Med,2007,35(6):1021-1035.
[5]姜宇懋,王丹巧.川芎嗪药理作用研究进展[J].中国现代中药,2016,18(10):1364-1370.
[6]Ji X Y,Tan B K,Zhu Y Z.Salvia miltiorrhiza and ischemic diseases[J].Acta Pharmacol Sin,2000,21(12):1089-1094.
[7]Lam F F,Yeung J H,Chan K M,et al.Relaxant effects of danshen aqueous extract and its constituent danshensu on rat coronary artery are mediated by inhibition of calcium channels[J].Vascul Pharmacol,2007,46(4):271-277.
[8]陈俞材,方莲花,杜冠华.丹参水溶性化合物抗心肌缺血作用的研究进展[J].中国药理学通报,2015,31(2):162-165.
[9]Huang W,Yang Y,Zeng Z,et al.Effect of Salvia miltiorrhiza and ligustrazine injection on myocardial ischemia/reperfusion and hypoxia/reoxygenation injury[J].Mol Med Rep,2016,14(5):4537-4544.
[10]黄文东,杨永飞,陈建文,等.丹参素与川芎嗪对心血管系统的协同作用[J].中国药理学通报,2013,29(3):432-436.
[11]高琦,黄文东,苏妹玲,等.丹羚心舒胶囊对大鼠离体心脏缺血/再灌注损伤的保护作用[J].国际病理科学与临床杂志,2014,34(6):731-737.
[12]Reimer KA,Jennings RB,Tatum AH.Pathobiology of acute myocardial ischemia:metabolic,functional and ultrastructural studies[J].Am J Cardiol,1983,52(2):72-81.
[13]Classen JB,Mergner WJ,Costa M.ATP hydrolysis by ischemic mitochondria[J].J Cell Physiol,1989,141(1):53-59.
[14]陈晓光,马虹,王俊科,等.肢体缺血预处理对缺血/再灌注心肌保护作用及其机制[J].中国药理学通报,2007,23(11):1490-1493.
[15]Rajadurai M,Stanely MPP.Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenolinduced cardiotoxicity in Wistar rats:biochemical and histopathological evidences[J].Toxicology,2006,228(2-3):259-268.
[16]李庆林,王成永,彭代银,等.黄蜀葵花总黄酮对心肌缺血再灌注损伤的保护作用研究[J].中国实验方剂学杂志,2006,12(2):39-42.
[17]张建军,张振英,王娜.羟基红花黄色素A对大鼠心肌缺血再灌注损伤的保护作用及机制[J].中国医院药学杂志,2012,32(19):1526-1530.
[18]孙鸿.心脏型脂肪酸结合蛋白在早期心肌损伤中的诊断价值[J].山西医药杂志,2014,43(22):2666-2668.
[19]苏其利,朱平,庄建,等.氧化应激与缺血性心肌病的研究进展[J].岭南心血管病杂志,2017,23(5):628-632.
[20]赵潇然,张凤如.心肌再灌注损伤的机制与治疗策略[J].国际心血管病杂志,2014,23(3):158-160.
[21]李定友,邓汉武,陈修.卡托普利保护大鼠缺血再灌注心肌与抗心肌脂质过氧化的关系(英文)[J].中国药理学与毒理学杂志,1989,3(3):212-217.
[22]Garcia-Gil F A,Gonzalvo E,Garcia-Garcia J J,et al.Lipid peroxidation in ischemia-reperfusion oxidative injury of the graft preserved in Celsior and University of Wisconsin solutions on a pig pancreas transplantation model[J].Transplant Proc,2006,38(8):2595-2599.
[23]刘筱蔼,刘国辉,陈燕斐,等.四逆汤对缺血-再灌注离体鼠肺的保护作用[J].中国病理生理杂志,2008,24(4):680-682.
[2]陈福晖,刘达兴,容松.心肌缺血再灌注损伤发生机制的研究进展[J].安徽医药,2017(12):2145-2148.
[3]贺常萍,张家兵.急性心肌梗死再灌注治疗的研究进展[J].医学综述,2018,25(12):2394-2400.
[4]Wong KL,Wu KC,Wu RS,et al.Tetramethylpyrazine inhibits angiotensin II-increased NAD(P)H oxidase activity and subsequent proliferation in rat aortic smooth muscle cells[J].Am J Chin Med,2007,35(6):1021-1035.
[5]姜宇懋,王丹巧.川芎嗪药理作用研究进展[J].中国现代中药,2016,18(10):1364-1370.
[6]Ji X Y,Tan B K,Zhu Y Z.Salvia miltiorrhiza and ischemic diseases[J].Acta Pharmacol Sin,2000,21(12):1089-1094.
[7]Lam F F,Yeung J H,Chan K M,et al.Relaxant effects of danshen aqueous extract and its constituent danshensu on rat coronary artery are mediated by inhibition of calcium channels[J].Vascul Pharmacol,2007,46(4):271-277.
[8]陈俞材,方莲花,杜冠华.丹参水溶性化合物抗心肌缺血作用的研究进展[J].中国药理学通报,2015,31(2):162-165.
[9]Huang W,Yang Y,Zeng Z,et al.Effect of Salvia miltiorrhiza and ligustrazine injection on myocardial ischemia/reperfusion and hypoxia/reoxygenation injury[J].Mol Med Rep,2016,14(5):4537-4544.
[10]黄文东,杨永飞,陈建文,等.丹参素与川芎嗪对心血管系统的协同作用[J].中国药理学通报,2013,29(3):432-436.
[11]高琦,黄文东,苏妹玲,等.丹羚心舒胶囊对大鼠离体心脏缺血/再灌注损伤的保护作用[J].国际病理科学与临床杂志,2014,34(6):731-737.
[12]Reimer KA,Jennings RB,Tatum AH.Pathobiology of acute myocardial ischemia:metabolic,functional and ultrastructural studies[J].Am J Cardiol,1983,52(2):72-81.
[13]Classen JB,Mergner WJ,Costa M.ATP hydrolysis by ischemic mitochondria[J].J Cell Physiol,1989,141(1):53-59.
[14]陈晓光,马虹,王俊科,等.肢体缺血预处理对缺血/再灌注心肌保护作用及其机制[J].中国药理学通报,2007,23(11):1490-1493.
[15]Rajadurai M,Stanely MPP.Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenolinduced cardiotoxicity in Wistar rats:biochemical and histopathological evidences[J].Toxicology,2006,228(2-3):259-268.
[16]李庆林,王成永,彭代银,等.黄蜀葵花总黄酮对心肌缺血再灌注损伤的保护作用研究[J].中国实验方剂学杂志,2006,12(2):39-42.
[17]张建军,张振英,王娜.羟基红花黄色素A对大鼠心肌缺血再灌注损伤的保护作用及机制[J].中国医院药学杂志,2012,32(19):1526-1530.
[18]孙鸿.心脏型脂肪酸结合蛋白在早期心肌损伤中的诊断价值[J].山西医药杂志,2014,43(22):2666-2668.
[19]苏其利,朱平,庄建,等.氧化应激与缺血性心肌病的研究进展[J].岭南心血管病杂志,2017,23(5):628-632.
[20]赵潇然,张凤如.心肌再灌注损伤的机制与治疗策略[J].国际心血管病杂志,2014,23(3):158-160.
[21]李定友,邓汉武,陈修.卡托普利保护大鼠缺血再灌注心肌与抗心肌脂质过氧化的关系(英文)[J].中国药理学与毒理学杂志,1989,3(3):212-217.
[22]Garcia-Gil F A,Gonzalvo E,Garcia-Garcia J J,et al.Lipid peroxidation in ischemia-reperfusion oxidative injury of the graft preserved in Celsior and University of Wisconsin solutions on a pig pancreas transplantation model[J].Transplant Proc,2006,38(8):2595-2599.
[23]刘筱蔼,刘国辉,陈燕斐,等.四逆汤对缺血-再灌注离体鼠肺的保护作用[J].中国病理生理杂志,2008,24(4):680-682.