川芎嗪对兔急性心肌梗死血运重建后心肌“无复流”现象影响的实验研究
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摘要
目的：观察川芎嗪对兔急性心肌梗死血运重建后心肌“无复流”现象的影响。
方法：新西兰大白兔45只，体重2.8～3.2kg，雌雄不拘，随机分为川芎嗪组(Ⅰ组)、尼可地尔对照组(Ⅱ组)、生理盐水对照组(Ⅲ组)，每组15只。开胸结扎左室后降支形成急性心肌梗死模型，以同步心电图出现ST-T弓背向上抬高为结扎有效；结扎90min后，切断结扎线重建血运，然后Ⅰ、Ⅱ、Ⅲ组分别经静脉给予川芎嗪(首先以2mg·kg~(-1)静脉注射，然后按0.3mg·kg~(-1)·min~(-1)速度持续静脉滴注)、尼可地尔(按0.2·kg~(-1)·min~(-1)速度持续静脉滴注)、生理盐水(按0.3ml·kg~(-1)·min~(-1)速度持续静脉滴注)，连续静滴120分钟。于结扎前10min、结扎后90min、血运重建后120min从颈静脉采血，分别测定心肌磷酸肌酶(CK)、乳酸脱氢酶(LDH)、超氧化物岐化酶(SOD)和丙二醛(MDA)。血运重建后120min时左心房注射6％Thioflavin S荧光染色剂1ml，5min后迅速剪下心脏。游离左心室并冷冻40min，将左心室以1mm间隔平行于左房室环进行横断面切片(8-9片)。在紫外灯照射下区分“无复流”区(No-reflow Area，NRA，非荧光区)和血流灌注区(荧光区)；经TTC染色后区分梗死区(Myocardial infarction Area，MIA，白色区)和非坏死区(砖红色区)。观察指标：心肌无复流面积以NRA占左室面积(LVA)百分比表示；心肌梗死面积，以MIA／LVA表示：药物干预前后心电图ST段变化，以相关导联ST段抬高指数(∑STI)表示；药物干预前后血清LDH、CK、SOD和MDA；治疗过程中致命心律失常发生率和死亡率。
结果：1．NRA／LVA：Ⅰ组、Ⅱ组均显著小于Ⅲ组(P均＜0.05)；Ⅰ组与Ⅱ组间
中文摘要
比较无显著差异(P)0.05)。2.MIA/LVA:I组、11组均显著小于111组(P均(0.01);
I组与11组lhj无显著差异(P)0.05)。3.艺STI:结扎前smin和结扎后gomin，各
组间同步比较无显著性差异;血运重建后12Omin比较I组、H组均显著小于111
组(P均(0.01);I组与11组比较无显著差异(P)0.05)。各组血管再通后12Omin
时的艺STI均较结扎gomin时均有降低(P均<0.001)，降低幅度(艺STI杏，mv)以I
组最大，
n组次之，
LDH、MDA、SOD:
，111组最小(I组
结扎前和结扎后
vs 111组:P(0.01;11组vs 111组:P<0.01)。4.CK、
gomin各组间同步比较无显著性差异;血运重建
后12Omin比较
组vs 111组P(0.
CK和LDH:I组和11组均显著低于111组(CK:P均(0.01;
01;11组vs 111组P(0.05)，
组均显著低于11组(CK:
(P均(0 .01);MDA:I
LDH:I
P(0 .05
LDH:P(0.01);SOD:I组和11组均显著高于111组
组和11组
均显著低于111组(P均(0.01)，I组与11组的SOD和MDA无显著差异(P均)0.05)。
5.致命心律失常发生率和死亡率:I组无一例发生室颤、室速或死亡;H组室颤
l例，室速l例，无死亡;m组室颤2例，室速4例，死亡2例。
结论:川芍啧可显著减少兔心肌梗死血运重建后心肌无复流面积和心肌梗死面
积，减轻心肌损伤，且效果与尼可地尔相当。
OBJECTIVE To explore the effect of Liqustrazin on the no-reflow
phenomenon in rabbits undergoing acute coronary artery occlusion-reperfusion.
METHODS Rabbit' s acute ischemia- reperfusion model was carried out by
ligation of left post coronary descending artery and removing the ligation after occlusion of blood flow for 90min, followed by 120 min of reperfusion. Ligustrazine (group I , 2mg/kg bolus iv+0. 3mg.kg-1.min-1,n=15), Nicorandil (group II, 0.2.kg-1.min-1, n=15) and 0. 9% Nad saltsolution (NS) (group III, 0. 3ml.kg-1.min-1, n=15) were given intravenously after restoration of coronary blood flow and maintained for 120 min, respectively. The changes of electrocardiogram (ECG), activity of CK and LDH, amount of MDA and SOD in plasma were observed following acute ischemia and restoration of flow. 120 minutes after reperfusion, each rabbit was killed and its left ventricle (LV) was cut into 8-10 slices parallel to the atrioventricular groove. The no-reflow (NR) area and the infarct size (IS) were determined by thioflavin S and TTC staining at the end of the experiment respectively. The extent of NR and IS were expressed as percentage of LV.
RESULTS Ligustrazine and Nicorandil both resulted in a significant reduction in IS, NR, plasma levels of CK, LDH and MDA, while increase plasma level of SOD, in comparison with control animals.The extent of elevated ST segment in ECG (expressed as ESTI) in group I and II were both lower than that of group III (group I vs groupIII:P<0.01;group II vs groupIII: P<0.01) at the end of experiment. Comparing with nicorandil, Ligustrazine result in a
significant decrease in CK(p<0.05) and LDH (p<0.01), while there is no significant different in the effects on MDA, SOD and STI between two groups (p>0. 05).
CONCLUSION Ligustrazine can significantly decrease NR area and infarct size, make an important contribution to myocardial injury during postischemic reperfusion, and its effects are similar to that of nicorandil.
方法：新西兰大白兔45只，体重2.8～3.2kg，雌雄不拘，随机分为川芎嗪组(Ⅰ组)、尼可地尔对照组(Ⅱ组)、生理盐水对照组(Ⅲ组)，每组15只。开胸结扎左室后降支形成急性心肌梗死模型，以同步心电图出现ST-T弓背向上抬高为结扎有效；结扎90min后，切断结扎线重建血运，然后Ⅰ、Ⅱ、Ⅲ组分别经静脉给予川芎嗪(首先以2mg·kg~(-1)静脉注射，然后按0.3mg·kg~(-1)·min~(-1)速度持续静脉滴注)、尼可地尔(按0.2·kg~(-1)·min~(-1)速度持续静脉滴注)、生理盐水(按0.3ml·kg~(-1)·min~(-1)速度持续静脉滴注)，连续静滴120分钟。于结扎前10min、结扎后90min、血运重建后120min从颈静脉采血，分别测定心肌磷酸肌酶(CK)、乳酸脱氢酶(LDH)、超氧化物岐化酶(SOD)和丙二醛(MDA)。血运重建后120min时左心房注射6％Thioflavin S荧光染色剂1ml，5min后迅速剪下心脏。游离左心室并冷冻40min，将左心室以1mm间隔平行于左房室环进行横断面切片(8-9片)。在紫外灯照射下区分“无复流”区(No-reflow Area，NRA，非荧光区)和血流灌注区(荧光区)；经TTC染色后区分梗死区(Myocardial infarction Area，MIA，白色区)和非坏死区(砖红色区)。观察指标：心肌无复流面积以NRA占左室面积(LVA)百分比表示；心肌梗死面积，以MIA／LVA表示：药物干预前后心电图ST段变化，以相关导联ST段抬高指数(∑STI)表示；药物干预前后血清LDH、CK、SOD和MDA；治疗过程中致命心律失常发生率和死亡率。
结果：1．NRA／LVA：Ⅰ组、Ⅱ组均显著小于Ⅲ组(P均＜0.05)；Ⅰ组与Ⅱ组间
中文摘要
比较无显著差异(P)0.05)。2.MIA/LVA:I组、11组均显著小于111组(P均(0.01);
I组与11组lhj无显著差异(P)0.05)。3.艺STI:结扎前smin和结扎后gomin，各
组间同步比较无显著性差异;血运重建后12Omin比较I组、H组均显著小于111
组(P均(0.01);I组与11组比较无显著差异(P)0.05)。各组血管再通后12Omin
时的艺STI均较结扎gomin时均有降低(P均<0.001)，降低幅度(艺STI杏，mv)以I
组最大，
n组次之，
LDH、MDA、SOD:
，111组最小(I组
结扎前和结扎后
vs 111组:P(0.01;11组vs 111组:P<0.01)。4.CK、
gomin各组间同步比较无显著性差异;血运重建
后12Omin比较
组vs 111组P(0.
CK和LDH:I组和11组均显著低于111组(CK:P均(0.01;
01;11组vs 111组P(0.05)，
组均显著低于11组(CK:
(P均(0 .01);MDA:I
LDH:I
P(0 .05
LDH:P(0.01);SOD:I组和11组均显著高于111组
组和11组
均显著低于111组(P均(0.01)，I组与11组的SOD和MDA无显著差异(P均)0.05)。
5.致命心律失常发生率和死亡率:I组无一例发生室颤、室速或死亡;H组室颤
l例，室速l例，无死亡;m组室颤2例，室速4例，死亡2例。
结论:川芍啧可显著减少兔心肌梗死血运重建后心肌无复流面积和心肌梗死面
积，减轻心肌损伤，且效果与尼可地尔相当。
OBJECTIVE To explore the effect of Liqustrazin on the no-reflow
phenomenon in rabbits undergoing acute coronary artery occlusion-reperfusion.
METHODS Rabbit' s acute ischemia- reperfusion model was carried out by
ligation of left post coronary descending artery and removing the ligation after occlusion of blood flow for 90min, followed by 120 min of reperfusion. Ligustrazine (group I , 2mg/kg bolus iv+0. 3mg.kg-1.min-1,n=15), Nicorandil (group II, 0.2.kg-1.min-1, n=15) and 0. 9% Nad saltsolution (NS) (group III, 0. 3ml.kg-1.min-1, n=15) were given intravenously after restoration of coronary blood flow and maintained for 120 min, respectively. The changes of electrocardiogram (ECG), activity of CK and LDH, amount of MDA and SOD in plasma were observed following acute ischemia and restoration of flow. 120 minutes after reperfusion, each rabbit was killed and its left ventricle (LV) was cut into 8-10 slices parallel to the atrioventricular groove. The no-reflow (NR) area and the infarct size (IS) were determined by thioflavin S and TTC staining at the end of the experiment respectively. The extent of NR and IS were expressed as percentage of LV.
RESULTS Ligustrazine and Nicorandil both resulted in a significant reduction in IS, NR, plasma levels of CK, LDH and MDA, while increase plasma level of SOD, in comparison with control animals.The extent of elevated ST segment in ECG (expressed as ESTI) in group I and II were both lower than that of group III (group I vs groupIII:P<0.01;group II vs groupIII: P<0.01) at the end of experiment. Comparing with nicorandil, Ligustrazine result in a
significant decrease in CK(p<0.05) and LDH (p<0.01), while there is no significant different in the effects on MDA, SOD and STI between two groups (p>0. 05).
CONCLUSION Ligustrazine can significantly decrease NR area and infarct size, make an important contribution to myocardial injury during postischemic reperfusion, and its effects are similar to that of nicorandil.
引文
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