水芹水提取液抗心律失常的实验研究
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摘要
目的通过复制哇巴因诱发的大鼠心律失常模型,探讨水芹水提取液是否可显著对抗由哇巴因诱发的心律失常,以及其抗心律失常的作用机制。
方法选取67只SD大鼠,随机分为3组,即A组：生理盐水对照组(1 ml/kg),B组：水芹水提取液组(100mg/kg), C组：胺碘酮组(100mg/kg)。各组大鼠均以10%水合氯醛(0.35 ml/100 g)腹腔麻醉,待大鼠心电图稳定后,分别按要求于大鼠尾静脉注射生理盐水、水芹水提取液和胺碘酮注射液。5 min后,各组大鼠再于尾静脉注射哇巴因200μg/kg,并同步观察Ⅱ导联心电图,记录心律失常的开始时间及持续时间,以及各组中出现室早、室速和室颤的大鼠数目,分别计算各组大鼠室早、室速和室颤的发生率,并对心律失常的严重程度通过心律失常评分系统进行定量分析。至注射哇巴因30 min后停止记录心电图,分离大鼠心脏,准确称取1g心肌组织,并按1：9的重量体积比加生理盐水制成10%的组织匀浆,以1000 r/min离心10 min,然后取上清液0.1 ml加入0.9 ml生理盐水稀释成1%的组织匀浆。用考马司亮兰试剂测定1%心肌组织匀浆蛋白含量后,采用无机磷法测定心肌细胞膜上的Na+-K+-ATP酶活性。
结果1、各组大鼠心律失常开始时间比较：与A组(6.93±2.28 min)比较,B组、C组心律失常开始时间(9.10±3.09 min,9.06±2.88 min)均延迟,差异均有统计学意义(P=0.016,P=0.018)；B组心律失常开始时间较C组延迟,但差异无统计学意义(P=0.962)。2、各组大鼠心律失常持续时间比较：与A组(13.29±4.25 min)比较,B组、C组心律失常持续时间(9.84±3.54 min,9096±4.39min)均缩短,差异有统计学意义(P=0.010,P=0.013)；B组心律失常持续时间较C组稍短,但差异无统计学意义(P=0.927)。3、各组大鼠心律失常发生率比较：各组大鼠均出现室性早搏。B组、C组大鼠室速发生率(50%,45%)分别低于A组(90%),差异均有统计学意义(x2=7.62,P=0.006；x2=9.23,P=0.002)；B组与C组差异并无统计学意义(#=0.10,P=0.752)。B组、C组大鼠室颤发生率(40%,35%)分别低于A组(80%),差异均有统计学意义(x2=6.67,P=0.010；x2=8.29,P=0.004)；B组与C组差异并无统计学意义(x2=0.11,P=0.744)。其中,A组、B组、C组分别有9只、2只、2只大鼠因室颤而死亡。4、各组大鼠心律失常评分比较：A组、B组、C组心律失常平均评分分别为(3.65±0.81，2.55±1.36，2.40±1.35)。各组大鼠心律失常评分总体上有差别(P=0.004)。两两之间比较采用Nemenyi法检验得知：A组心律失常评分分别与B组、C组比较时,差异均有统计学意义(x2=7.02,P=0.030；x2=9.06,P=0.011)。B组与C组差异无统计学意义(x2=0.13,P=0.937)。5、各组大鼠心肌组织Na+-K+-ATP酶活性比较：B组、C组大鼠心肌组织Na+-K+-ATP酶活性(3.74±0.57 U/mgprot, 3.88±0.44 U/mgprot)分别高于A组(3.40±0.39 U/mgprot),差异均有统计学意义(P=0.029,P=0.002)。B组与C组差异无统计学意义(P=0.324)。
结论1、水芹水提取液能有效推迟大鼠心律失常的开始时间,缩短心律失常的持续时间,降低大鼠室速、室颤的发生率,降低心律失常评分。水芹水提取液具有明显的抗实验性心律失常作用,其疗效与胺碘酮注射液相当。2、水芹水提取液能提高大鼠心律失常模型心肌组织的Na+-K+-ATP酶活性。保护心肌细胞膜上的Na+-K+-ATP酶功能,可能是水芹水提取液抗心律失常的作用机制之一。
Objective By establishing an arrhythmia model induced by ouabain in SD rats, to study whether Oenanthe Stolonifera(Bl.)DC water extrat could significantly antagonize arrhythmia induced by ouabain in rats, and the antiarrhythmic mechanism of Oenanthe Stolonifera(Bl.)DC water extract.
Metheds 67 healthy adult rats were divided into 3 groups, namely, group A:normal saline control group(1ml/kg), group B:Oenanthe Stolonifera(Bl.)DC water extract treatment group(100 mg/kg), group C:Amiodarone treatment group(100 mg/kg). The rats were initially anesthetized with an intraperitoneal injection of 10% chloral hydrate (0.35 ml/100 g). After the rats'ECG was steady, rats in every group were injected with normal saline, Oenanthe Stolonifera(Bl.)DC water extract, amiodarone injection via tail vein as required respectively.5 minutes later, each rat received an injection of 200μg/kg ouabain via tail vein. then observeb standard limb leadⅡECG simultaneously, counted the onset time and duration of arrhythmia, and the number of rats which occured ventricular premature beats(VPB), ventricular tachycardia(VT) and ventricular fibrillation(VF), calculated the occurrence of VPB, VT and VF, quantitative analysis of the severity of arrhythmia by using arrhythmia score system.30 minutes after injection with ouabain, stoped recording the ECG, set apart the rats'heart, weighted 1 g myocardiac tissue accurately, and according to the ratio between weight and volume(1:9),10% homogenate was made by adding normal saline, then centrifuged at 1000 r/min for 10 minutes, obtained supernatant 0.1 ml, plused normal sodium 0.9 ml into it, the homogenate was diluted to 1%. Determined the protein content of myocardiac homogenate with coomassie brilliant blue, measured the activity of Na+-K+-ATPase on myocardiac membrane with using inorganic phosphorus method.
Results 1. the difference of the onset time of arrhythmia in every group:Compared with group A(6.93±2.28 min), group B and C could prolong the onset time of arrhythmia(9.10±3.09 min,9.06±2.88 min), the differences were also significant (P=0.016, P=0.018); the onset time of arrhythmia in group B was later than that in group C, but had no statistical significant(P=0.962).2. the difference of the duration of arrhythmia in every group:Compared with group A(13.29±4.25 min), group B and C could shorten the duration time of arrhythmia(9.84±3.54 min,9.96±4.39 min), the differences were also significant(P=0.010, P=0.013); the duration of arrhythmia in group B was shorten than that in group C, but had no statistical significant(P=0.927). 3. the difference of the occurence of arrhythmia in every group:SD rats in every group all occured ventricular premature beats. The occurrence of VT in group B and C(50%,45%) were lower than that of group A(90%) respectively, and the difference were also significant(χ2=7.62, P=0.006;χ2=9.23, P=0.002); there was no significant difference between group B and C(χ2=0.10, P=0.752). The occurence of VF in group B and C(40%,35%) were lower than that of group A(80%) respectively, and the difference were also significant(χ2=6.67, P=0.010;χ2=8.29, P=0.004); there was no significant difference between group B and C(χ2=0.11, P=0.744).9,2,2 rats were killed respectively in every group because of ventricular fibrillation.4. the difference of the arrhythmia score in every group:The average score of arrhythmia in group A, B and C was 3.65±0.81,2.55±1.36,2.40±1.35 respectively. Significant difference was found in the arrhythmia score of every group as a whole(P=0.004). The pairwise comparison was performed with Nemenyi method. The significant difference in the arrhythmia score were found between group A and B(χ2=7.02, P=0.030), group A and C(χ2=9.06, P=0.011). There was no significant difference between group B and C(χ2=0.13, P=0.937).5. the difference of the Na+-K+-ATPase's activity of myocardiac tissue in every group:The Na+-K+-ATPase's activity of myocardiac tissue in group B and C(3.74±0.57 U/mgprot,3.88±0.44 U/mgprot) were higher than that of group A(3.40±0.39 U/mgprot) respectively, and the difference were also significant (P=0.029; P=0.002). There was no significant difference between group B and C(P=0.324).
Conclusion 1. Oenanthe Stolonifera(Bl.)DC water extract could prolong the onset time of arrhythmia, reduce the duration of arrhythmia, decrease the occurrence of VT, VF and the arrhythmia score. Oenanthe Stolonifera(Bl.)DC water extract could significantly antagonize experimental arrhythmia, its curative effect equivalents with Amiodarone.2. Oenanthe Stolonifera(Bl.)DC water extract could enhance the Na+-K+-ATPase's activity of myocardiac tissue. Improving Na+-K+-ATPase activity on myocardial membrane is one the of mechanisms for its antagonizing arrhythmia.
方法选取67只SD大鼠,随机分为3组,即A组：生理盐水对照组(1 ml/kg),B组：水芹水提取液组(100mg/kg), C组：胺碘酮组(100mg/kg)。各组大鼠均以10%水合氯醛(0.35 ml/100 g)腹腔麻醉,待大鼠心电图稳定后,分别按要求于大鼠尾静脉注射生理盐水、水芹水提取液和胺碘酮注射液。5 min后,各组大鼠再于尾静脉注射哇巴因200μg/kg,并同步观察Ⅱ导联心电图,记录心律失常的开始时间及持续时间,以及各组中出现室早、室速和室颤的大鼠数目,分别计算各组大鼠室早、室速和室颤的发生率,并对心律失常的严重程度通过心律失常评分系统进行定量分析。至注射哇巴因30 min后停止记录心电图,分离大鼠心脏,准确称取1g心肌组织,并按1：9的重量体积比加生理盐水制成10%的组织匀浆,以1000 r/min离心10 min,然后取上清液0.1 ml加入0.9 ml生理盐水稀释成1%的组织匀浆。用考马司亮兰试剂测定1%心肌组织匀浆蛋白含量后,采用无机磷法测定心肌细胞膜上的Na+-K+-ATP酶活性。
结果1、各组大鼠心律失常开始时间比较：与A组(6.93±2.28 min)比较,B组、C组心律失常开始时间(9.10±3.09 min,9.06±2.88 min)均延迟,差异均有统计学意义(P=0.016,P=0.018)；B组心律失常开始时间较C组延迟,但差异无统计学意义(P=0.962)。2、各组大鼠心律失常持续时间比较：与A组(13.29±4.25 min)比较,B组、C组心律失常持续时间(9.84±3.54 min,9096±4.39min)均缩短,差异有统计学意义(P=0.010,P=0.013)；B组心律失常持续时间较C组稍短,但差异无统计学意义(P=0.927)。3、各组大鼠心律失常发生率比较：各组大鼠均出现室性早搏。B组、C组大鼠室速发生率(50%,45%)分别低于A组(90%),差异均有统计学意义(x2=7.62,P=0.006；x2=9.23,P=0.002)；B组与C组差异并无统计学意义(#=0.10,P=0.752)。B组、C组大鼠室颤发生率(40%,35%)分别低于A组(80%),差异均有统计学意义(x2=6.67,P=0.010；x2=8.29,P=0.004)；B组与C组差异并无统计学意义(x2=0.11,P=0.744)。其中,A组、B组、C组分别有9只、2只、2只大鼠因室颤而死亡。4、各组大鼠心律失常评分比较：A组、B组、C组心律失常平均评分分别为(3.65±0.81，2.55±1.36，2.40±1.35)。各组大鼠心律失常评分总体上有差别(P=0.004)。两两之间比较采用Nemenyi法检验得知：A组心律失常评分分别与B组、C组比较时,差异均有统计学意义(x2=7.02,P=0.030；x2=9.06,P=0.011)。B组与C组差异无统计学意义(x2=0.13,P=0.937)。5、各组大鼠心肌组织Na+-K+-ATP酶活性比较：B组、C组大鼠心肌组织Na+-K+-ATP酶活性(3.74±0.57 U/mgprot, 3.88±0.44 U/mgprot)分别高于A组(3.40±0.39 U/mgprot),差异均有统计学意义(P=0.029,P=0.002)。B组与C组差异无统计学意义(P=0.324)。
结论1、水芹水提取液能有效推迟大鼠心律失常的开始时间,缩短心律失常的持续时间,降低大鼠室速、室颤的发生率,降低心律失常评分。水芹水提取液具有明显的抗实验性心律失常作用,其疗效与胺碘酮注射液相当。2、水芹水提取液能提高大鼠心律失常模型心肌组织的Na+-K+-ATP酶活性。保护心肌细胞膜上的Na+-K+-ATP酶功能,可能是水芹水提取液抗心律失常的作用机制之一。
Objective By establishing an arrhythmia model induced by ouabain in SD rats, to study whether Oenanthe Stolonifera(Bl.)DC water extrat could significantly antagonize arrhythmia induced by ouabain in rats, and the antiarrhythmic mechanism of Oenanthe Stolonifera(Bl.)DC water extract.
Metheds 67 healthy adult rats were divided into 3 groups, namely, group A:normal saline control group(1ml/kg), group B:Oenanthe Stolonifera(Bl.)DC water extract treatment group(100 mg/kg), group C:Amiodarone treatment group(100 mg/kg). The rats were initially anesthetized with an intraperitoneal injection of 10% chloral hydrate (0.35 ml/100 g). After the rats'ECG was steady, rats in every group were injected with normal saline, Oenanthe Stolonifera(Bl.)DC water extract, amiodarone injection via tail vein as required respectively.5 minutes later, each rat received an injection of 200μg/kg ouabain via tail vein. then observeb standard limb leadⅡECG simultaneously, counted the onset time and duration of arrhythmia, and the number of rats which occured ventricular premature beats(VPB), ventricular tachycardia(VT) and ventricular fibrillation(VF), calculated the occurrence of VPB, VT and VF, quantitative analysis of the severity of arrhythmia by using arrhythmia score system.30 minutes after injection with ouabain, stoped recording the ECG, set apart the rats'heart, weighted 1 g myocardiac tissue accurately, and according to the ratio between weight and volume(1:9),10% homogenate was made by adding normal saline, then centrifuged at 1000 r/min for 10 minutes, obtained supernatant 0.1 ml, plused normal sodium 0.9 ml into it, the homogenate was diluted to 1%. Determined the protein content of myocardiac homogenate with coomassie brilliant blue, measured the activity of Na+-K+-ATPase on myocardiac membrane with using inorganic phosphorus method.
Results 1. the difference of the onset time of arrhythmia in every group:Compared with group A(6.93±2.28 min), group B and C could prolong the onset time of arrhythmia(9.10±3.09 min,9.06±2.88 min), the differences were also significant (P=0.016, P=0.018); the onset time of arrhythmia in group B was later than that in group C, but had no statistical significant(P=0.962).2. the difference of the duration of arrhythmia in every group:Compared with group A(13.29±4.25 min), group B and C could shorten the duration time of arrhythmia(9.84±3.54 min,9.96±4.39 min), the differences were also significant(P=0.010, P=0.013); the duration of arrhythmia in group B was shorten than that in group C, but had no statistical significant(P=0.927). 3. the difference of the occurence of arrhythmia in every group:SD rats in every group all occured ventricular premature beats. The occurrence of VT in group B and C(50%,45%) were lower than that of group A(90%) respectively, and the difference were also significant(χ2=7.62, P=0.006;χ2=9.23, P=0.002); there was no significant difference between group B and C(χ2=0.10, P=0.752). The occurence of VF in group B and C(40%,35%) were lower than that of group A(80%) respectively, and the difference were also significant(χ2=6.67, P=0.010;χ2=8.29, P=0.004); there was no significant difference between group B and C(χ2=0.11, P=0.744).9,2,2 rats were killed respectively in every group because of ventricular fibrillation.4. the difference of the arrhythmia score in every group:The average score of arrhythmia in group A, B and C was 3.65±0.81,2.55±1.36,2.40±1.35 respectively. Significant difference was found in the arrhythmia score of every group as a whole(P=0.004). The pairwise comparison was performed with Nemenyi method. The significant difference in the arrhythmia score were found between group A and B(χ2=7.02, P=0.030), group A and C(χ2=9.06, P=0.011). There was no significant difference between group B and C(χ2=0.13, P=0.937).5. the difference of the Na+-K+-ATPase's activity of myocardiac tissue in every group:The Na+-K+-ATPase's activity of myocardiac tissue in group B and C(3.74±0.57 U/mgprot,3.88±0.44 U/mgprot) were higher than that of group A(3.40±0.39 U/mgprot) respectively, and the difference were also significant (P=0.029; P=0.002). There was no significant difference between group B and C(P=0.324).
Conclusion 1. Oenanthe Stolonifera(Bl.)DC water extract could prolong the onset time of arrhythmia, reduce the duration of arrhythmia, decrease the occurrence of VT, VF and the arrhythmia score. Oenanthe Stolonifera(Bl.)DC water extract could significantly antagonize experimental arrhythmia, its curative effect equivalents with Amiodarone.2. Oenanthe Stolonifera(Bl.)DC water extract could enhance the Na+-K+-ATPase's activity of myocardiac tissue. Improving Na+-K+-ATPase activity on myocardial membrane is one the of mechanisms for its antagonizing arrhythmia.
引文
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[2]裴德安,李庚山,蒋锡嘉等.关附甲素对单个心室肌细胞钠通道的频率依赖性和使用依赖性阻滞作用[J].中国心脏起搏与心电生理杂志,1998,12(1)：49-50.
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[4]丽英,杨艳敏,浦介麟等.盐酸关附甲素对豚鼠心室肌细胞膜钠通道的阻断作用[J].中华心律失常学杂志,2007,1(11)：47-52.
[5]杨艳敏,朱俊,高鑫等.盐酸关附甲素注射液治疗室性心律失常的多中心随机开放实验[J].中华心律失常学杂志,2006,10(2)：130-134.
[6]黄从新,丁仲如,李庚山等.当归提取液对豚鼠心室肌细胞钠、钙离子通道的影响[J].中国心脏与心电生理杂志,1997,11(2)：96-98.
[7]周彤,毛晓波,毛奕等.阿魏酸钠对家兔心室肌细胞钾通道电流的影响[J].临床心血管杂志,2009,25(8)：588-592.
[8]张静,史茂伟,王冬梅等.黄芪对急性心肌梗死兔心室肌细胞L-钙通道电流的影响[J].中国药学杂志,2007,42(3)：234-234.
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[11]Du GH, Zhang JT. The general situation and progress of the modern research of red sage root (Radix Salviae miltiorrhizae) [J.]. Herald of Medicine,2004,23(1):356.
[12]陈旭华,徐岩.丹参对缺血心肌细胞离子通道的作用[J].安徽医科大学学报,2002,37(6)：450.
[13]苗维纳,沈映君,曾晓荣等.葛根素对豚鼠心室肌细胞钾离子通道的影响.中国应用生理学杂志[J],2002,18(2)：155-158.
[14]郭晓纲,陈君柱,张雄等.葛根素对大鼠心肌细胞L型钙离子通道的影响[J].中国中药杂志,2004,29(3)：249-251.
[15]陈悦,黄霞,卫琮玲.葛根素对豚鼠乳头肌动作电位及延迟整流钾电流的影响[J].中国药学杂志,2006,41(10)：747-749.
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