苗药理气活血滴丸对心肌缺血再灌注大鼠左心室肌细胞损伤的防护作用
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摘要
目的:研究苗药理气活血滴丸对心肌缺血再灌注损伤(MIRI)大鼠心肌的防护机制。方法:将SD大鼠随机分为假手术组、MIRI模型组、理气活血滴丸(175 mg/kg)组和辛伐他汀(40 mg/kg)组。给药组连续灌胃10天,假手术组和MIRI模型组大鼠灌胃等量的生理盐水。末次给药45 min后采用结扎冠状动脉左前降支方法复制MIRI大鼠模型。复灌后监测左心功能;取左心室利用透射电镜观察心肌细胞超微结构;TUNEL-POD法检测心肌细胞凋亡;荧光素酶法检测心肌组织ATP含量;提取心肌细胞线粒体;硫代巴比妥酸法测定心肌细胞线粒体丙二醛(MDA)含量;WST-8法测定线粒体超氧化物歧化酶(SOD)活性情况。结果:与MIRI模型组比较,理气活血滴丸(175 mg/kg)组大鼠左心功能和左心室肌细胞超微结构明显改善;线粒体损伤减轻;细胞凋亡发生率减少;心肌组织ATP含量升高;心肌细胞线粒体MDA含量降低;SOD活性升高。结论:理气活血滴丸对MIRI模型大鼠的防护机制与其改善左心室肌细胞超微结构、抑制细胞凋亡和减轻线粒体氧化损伤有关。
Objective: To study the protective mechanism of Liqihuoxue dripping pill against myocardial ischemia reperfusion injury(MIRI) in rats. Methods: Sprauge-Dawley rats were randomized into four groups,including the sham group,MIRI model group,Liqihuoxue dripping pill(175 mg/kg) group and simvatatin(40 mg/kg) group. Rats in each group were intragastrically given drugs for 10 days,once a day.Rats in the sham group and model group were given the same amount of saline. MIRI rat model was established by ligating the left anterior descending coronary artery 45 minutes after gavage. Left ventricular function was observed after ischemia-reperfusion,and left ventricles were collected. The ultrastructure of the cardial myocytes was observed. Apoptosis of myocardial cells was detected by TUNEL. ATP level of myocardial cells was determined by luciferase method. After the mitochodria dissociated,MDA content in the mitochondria was measured by thiobabituric acid assay,and the activity of superoxide dismutase(SOD) was measured by WST-8. Results: The left ventricular function and left ventricular myocytes ultrastructure were significantly improved in Liqihuoxue dripping pill group compared with those in the model group. Moreover,mitochonodrial injury was obviously ameliorated,the incidence of apoptosis was significantly reduced and the content of ATP in myocardium tissues was obviously high,compared with those in the model group,respectively. The content of MDA in myocardial cells mitochondria was decreased and the activity of SOD was increased. Conclusion: The protective mechanism of Liqihuoxue dripping pill on MIRI model rats is related to improving the ultrastructure of left ventricular myocytes,inhibiting apoptosis and mitigating mitochondrial oxidative damage.
Objective: To study the protective mechanism of Liqihuoxue dripping pill against myocardial ischemia reperfusion injury(MIRI) in rats. Methods: Sprauge-Dawley rats were randomized into four groups,including the sham group,MIRI model group,Liqihuoxue dripping pill(175 mg/kg) group and simvatatin(40 mg/kg) group. Rats in each group were intragastrically given drugs for 10 days,once a day.Rats in the sham group and model group were given the same amount of saline. MIRI rat model was established by ligating the left anterior descending coronary artery 45 minutes after gavage. Left ventricular function was observed after ischemia-reperfusion,and left ventricles were collected. The ultrastructure of the cardial myocytes was observed. Apoptosis of myocardial cells was detected by TUNEL. ATP level of myocardial cells was determined by luciferase method. After the mitochodria dissociated,MDA content in the mitochondria was measured by thiobabituric acid assay,and the activity of superoxide dismutase(SOD) was measured by WST-8. Results: The left ventricular function and left ventricular myocytes ultrastructure were significantly improved in Liqihuoxue dripping pill group compared with those in the model group. Moreover,mitochonodrial injury was obviously ameliorated,the incidence of apoptosis was significantly reduced and the content of ATP in myocardium tissues was obviously high,compared with those in the model group,respectively. The content of MDA in myocardial cells mitochondria was decreased and the activity of SOD was increased. Conclusion: The protective mechanism of Liqihuoxue dripping pill on MIRI model rats is related to improving the ultrastructure of left ventricular myocytes,inhibiting apoptosis and mitigating mitochondrial oxidative damage.
引文
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2 李尧锋,徐剑,陈向云,等.苗药理气活血滴丸对心肌缺血再灌注损伤模型大鼠的保护作用.中国药房,2017;28(1)∶76~79
3 李尧锋,彭芳,陈向云,等.理气活血滴丸对心肌缺血再灌注损伤大鼠心肌组织形态学和抗氧化性的影响.中国民族民间医药,2017;26(15)∶54~57
4 Lesnefsky E J,Chen Q,Tandler B,et al.Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion:Implications for Novel Therapies.Annual review of pharmacology and toxicology,2017;57(1)∶535~565
5 王淑侠,兰小莉,王吉文.大鼠心肌缺血/再灌注损伤模型的改进与评价.解剖科学进展,2000;6(4)∶371~373
6 王艳飞,曹雪滨,崔英凯,等.改良大鼠左心室插管术及心衰大鼠左心功能指标的测定.中国比较医学杂志,2008;18(12)∶34~36
7 Parlakpinar H,Orum M H,Sagir M.Pathophysiology of Myocardial Ischemia Reperfusion Injury∶A Review.Medicine Science,2013;2(4)∶935 ~954
8 Jones S P,Trocha S D,Lefer D J.Pretreatment with simvastatin attenuates myocardial dysfunction after ischemia and chronic reperfusion.Arterioscler Thromb Vasc Biol,2001;21(12)∶2059~2064
9 Wayman N S,Ellis B L,Thiemermann C.Simvastatin reduces infarct size in a model of acute myocardial ischemia and reperfusion in the rat.Med Sci Monit,2003,9(5)∶155~159
10 Tavackoli S,Ashitkov T,Hu Z Y,et al.Simvastatin-induced myocardial protection against ischemia-reperfusion injury is mediated by activation of ATP-sensitive K+channels.Coron Artery Dis,2004;15(1)∶53~58
11 Hadi N R,Yousif F G,Zamil S T.The effect of Simvastatin in attenuation of Myocardial,Ischemia/Reperfusion injury.Knowledge Engineering Review,2013,14(14)∶181~185
12 李光,邢小燕,张美双,等.基于表观遗传学调控的中医药防治心肌缺血再灌注损伤的研究进展.药学学报,2016;51(7)∶1047~1053
13 张宇,李建锋,单红燕,等.中药调节心肌缺血再灌注损伤的活性成分及作用机制.辽宁中医杂志,2016;43(08)∶1709~1713
14 李冀,丁莹,王呈祥,等.浅谈心肌缺血再灌注损伤的中医新进展.中医药学报,2016;44(2)∶105~107
15 孙刚,周琦.理气活血滴丸治疗冠心病心绞痛的临床疗效.临床合理用药杂志,2016;9(3)∶141~142
16 Wakabayashi T,Karbowski M.Structural changes of mitochondria related to apoptosis.Biol Signals Recept,2001;10(1-2)∶26~56
17 Raha S,Robinson B H.Mitochondria,oxygen free radicals,and apoptosis.American Journal of Medical Genetics,2001;106(1)∶62~70
18 Petrosillo G,Di V N,Ruggiero F M,et al.Mitochondrial dysfunction associated with cardiac ischemia/reperfusion can be attenuated by oxygen tension control.Role of oxygen-free radicals and cardiolipin.Biochimica Et Bio-physica Acta,2005;1710(2)∶78~86
2 李尧锋,徐剑,陈向云,等.苗药理气活血滴丸对心肌缺血再灌注损伤模型大鼠的保护作用.中国药房,2017;28(1)∶76~79
3 李尧锋,彭芳,陈向云,等.理气活血滴丸对心肌缺血再灌注损伤大鼠心肌组织形态学和抗氧化性的影响.中国民族民间医药,2017;26(15)∶54~57
4 Lesnefsky E J,Chen Q,Tandler B,et al.Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion:Implications for Novel Therapies.Annual review of pharmacology and toxicology,2017;57(1)∶535~565
5 王淑侠,兰小莉,王吉文.大鼠心肌缺血/再灌注损伤模型的改进与评价.解剖科学进展,2000;6(4)∶371~373
6 王艳飞,曹雪滨,崔英凯,等.改良大鼠左心室插管术及心衰大鼠左心功能指标的测定.中国比较医学杂志,2008;18(12)∶34~36
7 Parlakpinar H,Orum M H,Sagir M.Pathophysiology of Myocardial Ischemia Reperfusion Injury∶A Review.Medicine Science,2013;2(4)∶935 ~954
8 Jones S P,Trocha S D,Lefer D J.Pretreatment with simvastatin attenuates myocardial dysfunction after ischemia and chronic reperfusion.Arterioscler Thromb Vasc Biol,2001;21(12)∶2059~2064
9 Wayman N S,Ellis B L,Thiemermann C.Simvastatin reduces infarct size in a model of acute myocardial ischemia and reperfusion in the rat.Med Sci Monit,2003,9(5)∶155~159
10 Tavackoli S,Ashitkov T,Hu Z Y,et al.Simvastatin-induced myocardial protection against ischemia-reperfusion injury is mediated by activation of ATP-sensitive K+channels.Coron Artery Dis,2004;15(1)∶53~58
11 Hadi N R,Yousif F G,Zamil S T.The effect of Simvastatin in attenuation of Myocardial,Ischemia/Reperfusion injury.Knowledge Engineering Review,2013,14(14)∶181~185
12 李光,邢小燕,张美双,等.基于表观遗传学调控的中医药防治心肌缺血再灌注损伤的研究进展.药学学报,2016;51(7)∶1047~1053
13 张宇,李建锋,单红燕,等.中药调节心肌缺血再灌注损伤的活性成分及作用机制.辽宁中医杂志,2016;43(08)∶1709~1713
14 李冀,丁莹,王呈祥,等.浅谈心肌缺血再灌注损伤的中医新进展.中医药学报,2016;44(2)∶105~107
15 孙刚,周琦.理气活血滴丸治疗冠心病心绞痛的临床疗效.临床合理用药杂志,2016;9(3)∶141~142
16 Wakabayashi T,Karbowski M.Structural changes of mitochondria related to apoptosis.Biol Signals Recept,2001;10(1-2)∶26~56
17 Raha S,Robinson B H.Mitochondria,oxygen free radicals,and apoptosis.American Journal of Medical Genetics,2001;106(1)∶62~70
18 Petrosillo G,Di V N,Ruggiero F M,et al.Mitochondrial dysfunction associated with cardiac ischemia/reperfusion can be attenuated by oxygen tension control.Role of oxygen-free radicals and cardiolipin.Biochimica Et Bio-physica Acta,2005;1710(2)∶78~86