养心颗粒对实验性快速型心律失常模型心肌ATP敏感性钾通道影响的研究
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摘要
目的：通过观察养心颗粒对实验性快速型心律失常动物模型心电图、血脂、主动脉病理形态学和超微结构的变化；观察对心肌细胞缝隙连接蛋白43以及ATP敏感性钾通道的影响，探讨其防治心律失常的确切作用机制，为今后临床应用提供客观依据。
方法：将90只大鼠随机各分为3组：空白对照组、养心颗粒组、阳性药物对照组，每组各10只，在第3天灌服药物1小时后，分别采用氯化钡及乌头碱静脉注射、结扎冠状动脉等方法诱发大鼠快速性心律失常。将高脂饮食喂养8周后的28只家兔随机分为模型对照组、养心颗粒防治组、养心颗粒治疗组、胺碘酮对照组，每组各7只，另取7只家兔做为空白对照组，于末次灌胃1小时后静脉注射肾上腺素。常规观察Ⅱ导联心电图心律失常出现的时间、持续时间；血脂含量的变化；主动脉病理形态学及超微结构变化；免疫组化法检测心肌缝隙连接蛋白43的表达情况：RT-PCR法测定心肌ATP敏感性钾通道的表达情况。
结果：1心电图显示：①养心颗粒能推迟氯化钡所致大鼠心动过速的发生时间，缩短心电图的恢复时间，与空白对照组比较有明显差异(p＜0.01)；能延缓乌头碱所致大鼠心律失常的出现时间，减少持续时间，与空白对照组比较差异有统计学意义(p＜0.01)；能延迟冠脉结扎大鼠心律失常的出现时间，显著缩短心律失常持续时间，明显降低室性心动过速发生率，与空白对照组比较差异有统计学意义(p＜0.01)，与普罗帕酮组作用相当；②能延缓家兔快速型心律失常模型的出现时间，减少持续时间，且养心颗粒防治组与养心颗粒治疗组、模型对照组比较差异有统计学意义(p＜0.01)，与胺碘酮组比较差异无统计学意义(p＞0.05)。2．血脂含量测定显示：养心颗粒防治组与模型对照组相比，TG、CHO、ApoB均有显著下降，差异有统计学意义(p＜0.05)，HDL-C、ApoA有所升高，差异有统计学意义(p＜0.05)。3．光镜观察：养心颗粒防治组主动脉内皮细胞轻度减少，内膜较增厚，内膜下有脂质沉积，血管平滑肌排列轻度紊乱较其他组变化轻。4．电镜观察：养心颗粒防治组主动脉表层内皮细胞脂质物质沉积，细胞器结构不清晰，中膜肌纤维排列规则，胶原纤维与细胞凸起缠绕在一起较其他组损伤明显减轻。5．免疫组化观测显示：养心颗粒防治组缝隙连接蛋白43表达明显增高，着色斑点大小较一致、分布较均一。图像半定量结果分析养心颗粒防治组缝隙连接蛋43表达增加，与胺碘酮组比较差异无统计学意义(p＞0.05)，而与其他各组比较差异有统计学意义(p＜0.01)。6．RT-PCR检测显示：养心颗粒治疗组、养心颗粒防治组和胺碘酮组与模型对照组比较K_(ATP)mRNA／β-action mRNA比值显著降低，差异有统计学意义(p＜0.01)，尤以养心颗粒防治组和胺碘酮组疗效为佳。
结论：养心颗粒能够明显延缓氯化钡、乌头碱以及冠脉结扎大鼠以及高脂饮食并肾上腺素诱发家兔实验性心律失常出现的时间、缩短其恢复时间；养心颗粒可改善模型家兔的血脂异常和主动脉粥样硬化的病理形态学及超微结构异常，发挥抗动脉粥样硬化的作用；养心颗粒可以上调家兔心肌缝隙连接43蛋白的表达，下调ATP敏感性钾通道K_(ATP)mRNA的表达，起到防治快速型心律失常的作用。
Objective: To explore the cure mechanism of recuperating-heartgranule on arrhythmic by the study of observing the effect of ECG,blood-serum; pathomorph of cardiac muscle, cardiac muscle cell of cx43proteinum,andATP sensitivity potassium channels when it affect experimentarrhythmic rat and rabbit.
Method: The use of Bacl2, aconitine, coronary artery ligation in ratsinduced by rapid methods such as three kinds of arrhythmia, as well asexperimental animal models in rabbits fed high-fat combination ofintravenous epinephrine to copy the methods of rapid coronary heartarrhythmia model,Ⅱobserved ECG arrhythmia occurred, duration, changesin lipid content,Pathomorphologic aorta, as well as institutional changesSupermicro, Immunohistochemical detection of myocardial cx43 proteinexpression; RT-PCR determination of the impact of channel KATPmRNA.
Results: 1.ECG showed: recuperating-heart granule can delay bacl2due to the occurrence of tachycardia in rats time to speed up the recoverytime electrocardiogram, Compared with blank control group significantdifference (P＜0.01)。Can delay the aconitine-induced arrhythmia in rats thetime to reduce the duration, and other group differences were significant (P＜0.01); Coronary artery ligation in rats can delay the emergence ofarrhythmia time, significantly shortening the duration of arrhythmia,significantly reduced the incidence of VT, compared with the control groupwere statistically significant differences (P＜0.01), Propafenone group witha considerable role, Can delay the emergence of coronary heart diseasearrhythmias time, reduce the duration and control group recuperating-heartgranule and recuperating-heart granule treatment group, model group, thedifference was statistically significant ((P＜0.01)), Compared with theamiodarone group was no significant difference (p＞0.05)
2.Lipids assay showed: recuperating-heart granule model control group and compared to the control group, TG, CHO, ApoB were significantlydecreased, the difference was statistically significant (P＜0.05), HDL-C,ApoA has increased, the difference was statistically significant ( P＜0.05).
3.Light microscope: recuperating-heart granule control group with mildreduction in aortic endothelial cells, intimal thickening than intimal lipiddeposition under, vascular smooth muscle disorder with mild changes in lightthan the other groups (except the blank group).
4.Electron microscope: recuperating-heart granule control groupaortic endothelial cells in the lower surface of lipid deposition material, cellstructure is not clear, in the muscle fiber membrane with the rules ofcollagen fibers and cell protruding intertwined than the other group (exceptthe blank group) significantly reduce the injury.
5.Immunohistochemistry showed: recuperating-heart granule controlgroup aizoon Cx43 expression was significantly higher than the same coloreddot size, the more uniform distribution. The results of semi-quantitativeimage analysis of recuperating-heart granule cx43 expression of controlgroup increased, and the blank group, model group, particle aizoondifference between the treatment group was statistically significant ((P＜0.01)), compared with the amiodarone group difference was not statisticallythe meaning of ((P＞0.05)).
6.RT-PCR detection showed that: recuperating-heart granule treatmentgroup and control group aizoon particles, amiodarone group compared withthe model control group KATP mRNA /β-action mRNA ratio significantlylower, the difference was statistically significant (P＜0.01),recuperating-heart granule control group and the amine iodine ketone groupwas no significant difference (P＞0.05).
Result:1. recuperating-heart granule of Bacl2, aconitine and coronaryartery ligation induced experimental arrhythmia arrhythmia and coronaryheart disease have a good Antagonism.2. recuperating-heart granuledyslipidemia particles can be improved to improve atherosclerosis and ultrastructural abnormalities pathomorphology to play anti-atherogenicrole.3, recuperating-heart granule may be increased 43 rabbit myocardial gapjunctional protein expression, reduced ATP-sensitive potassium channelKATP mRNA expression, prevention of coronary heart disease has played therole of rapid arrhythmia.
方法：将90只大鼠随机各分为3组：空白对照组、养心颗粒组、阳性药物对照组，每组各10只，在第3天灌服药物1小时后，分别采用氯化钡及乌头碱静脉注射、结扎冠状动脉等方法诱发大鼠快速性心律失常。将高脂饮食喂养8周后的28只家兔随机分为模型对照组、养心颗粒防治组、养心颗粒治疗组、胺碘酮对照组，每组各7只，另取7只家兔做为空白对照组，于末次灌胃1小时后静脉注射肾上腺素。常规观察Ⅱ导联心电图心律失常出现的时间、持续时间；血脂含量的变化；主动脉病理形态学及超微结构变化；免疫组化法检测心肌缝隙连接蛋白43的表达情况：RT-PCR法测定心肌ATP敏感性钾通道的表达情况。
结果：1心电图显示：①养心颗粒能推迟氯化钡所致大鼠心动过速的发生时间，缩短心电图的恢复时间，与空白对照组比较有明显差异(p＜0.01)；能延缓乌头碱所致大鼠心律失常的出现时间，减少持续时间，与空白对照组比较差异有统计学意义(p＜0.01)；能延迟冠脉结扎大鼠心律失常的出现时间，显著缩短心律失常持续时间，明显降低室性心动过速发生率，与空白对照组比较差异有统计学意义(p＜0.01)，与普罗帕酮组作用相当；②能延缓家兔快速型心律失常模型的出现时间，减少持续时间，且养心颗粒防治组与养心颗粒治疗组、模型对照组比较差异有统计学意义(p＜0.01)，与胺碘酮组比较差异无统计学意义(p＞0.05)。2．血脂含量测定显示：养心颗粒防治组与模型对照组相比，TG、CHO、ApoB均有显著下降，差异有统计学意义(p＜0.05)，HDL-C、ApoA有所升高，差异有统计学意义(p＜0.05)。3．光镜观察：养心颗粒防治组主动脉内皮细胞轻度减少，内膜较增厚，内膜下有脂质沉积，血管平滑肌排列轻度紊乱较其他组变化轻。4．电镜观察：养心颗粒防治组主动脉表层内皮细胞脂质物质沉积，细胞器结构不清晰，中膜肌纤维排列规则，胶原纤维与细胞凸起缠绕在一起较其他组损伤明显减轻。5．免疫组化观测显示：养心颗粒防治组缝隙连接蛋白43表达明显增高，着色斑点大小较一致、分布较均一。图像半定量结果分析养心颗粒防治组缝隙连接蛋43表达增加，与胺碘酮组比较差异无统计学意义(p＞0.05)，而与其他各组比较差异有统计学意义(p＜0.01)。6．RT-PCR检测显示：养心颗粒治疗组、养心颗粒防治组和胺碘酮组与模型对照组比较K_(ATP)mRNA／β-action mRNA比值显著降低，差异有统计学意义(p＜0.01)，尤以养心颗粒防治组和胺碘酮组疗效为佳。
结论：养心颗粒能够明显延缓氯化钡、乌头碱以及冠脉结扎大鼠以及高脂饮食并肾上腺素诱发家兔实验性心律失常出现的时间、缩短其恢复时间；养心颗粒可改善模型家兔的血脂异常和主动脉粥样硬化的病理形态学及超微结构异常，发挥抗动脉粥样硬化的作用；养心颗粒可以上调家兔心肌缝隙连接43蛋白的表达，下调ATP敏感性钾通道K_(ATP)mRNA的表达，起到防治快速型心律失常的作用。
Objective: To explore the cure mechanism of recuperating-heartgranule on arrhythmic by the study of observing the effect of ECG,blood-serum; pathomorph of cardiac muscle, cardiac muscle cell of cx43proteinum,andATP sensitivity potassium channels when it affect experimentarrhythmic rat and rabbit.
Method: The use of Bacl2, aconitine, coronary artery ligation in ratsinduced by rapid methods such as three kinds of arrhythmia, as well asexperimental animal models in rabbits fed high-fat combination ofintravenous epinephrine to copy the methods of rapid coronary heartarrhythmia model,Ⅱobserved ECG arrhythmia occurred, duration, changesin lipid content,Pathomorphologic aorta, as well as institutional changesSupermicro, Immunohistochemical detection of myocardial cx43 proteinexpression; RT-PCR determination of the impact of channel KATPmRNA.
Results: 1.ECG showed: recuperating-heart granule can delay bacl2due to the occurrence of tachycardia in rats time to speed up the recoverytime electrocardiogram, Compared with blank control group significantdifference (P＜0.01)。Can delay the aconitine-induced arrhythmia in rats thetime to reduce the duration, and other group differences were significant (P＜0.01); Coronary artery ligation in rats can delay the emergence ofarrhythmia time, significantly shortening the duration of arrhythmia,significantly reduced the incidence of VT, compared with the control groupwere statistically significant differences (P＜0.01), Propafenone group witha considerable role, Can delay the emergence of coronary heart diseasearrhythmias time, reduce the duration and control group recuperating-heartgranule and recuperating-heart granule treatment group, model group, thedifference was statistically significant ((P＜0.01)), Compared with theamiodarone group was no significant difference (p＞0.05)
2.Lipids assay showed: recuperating-heart granule model control group and compared to the control group, TG, CHO, ApoB were significantlydecreased, the difference was statistically significant (P＜0.05), HDL-C,ApoA has increased, the difference was statistically significant ( P＜0.05).
3.Light microscope: recuperating-heart granule control group with mildreduction in aortic endothelial cells, intimal thickening than intimal lipiddeposition under, vascular smooth muscle disorder with mild changes in lightthan the other groups (except the blank group).
4.Electron microscope: recuperating-heart granule control groupaortic endothelial cells in the lower surface of lipid deposition material, cellstructure is not clear, in the muscle fiber membrane with the rules ofcollagen fibers and cell protruding intertwined than the other group (exceptthe blank group) significantly reduce the injury.
5.Immunohistochemistry showed: recuperating-heart granule controlgroup aizoon Cx43 expression was significantly higher than the same coloreddot size, the more uniform distribution. The results of semi-quantitativeimage analysis of recuperating-heart granule cx43 expression of controlgroup increased, and the blank group, model group, particle aizoondifference between the treatment group was statistically significant ((P＜0.01)), compared with the amiodarone group difference was not statisticallythe meaning of ((P＞0.05)).
6.RT-PCR detection showed that: recuperating-heart granule treatmentgroup and control group aizoon particles, amiodarone group compared withthe model control group KATP mRNA /β-action mRNA ratio significantlylower, the difference was statistically significant (P＜0.01),recuperating-heart granule control group and the amine iodine ketone groupwas no significant difference (P＞0.05).
Result:1. recuperating-heart granule of Bacl2, aconitine and coronaryartery ligation induced experimental arrhythmia arrhythmia and coronaryheart disease have a good Antagonism.2. recuperating-heart granuledyslipidemia particles can be improved to improve atherosclerosis and ultrastructural abnormalities pathomorphology to play anti-atherogenicrole.3, recuperating-heart granule may be increased 43 rabbit myocardial gapjunctional protein expression, reduced ATP-sensitive potassium channelKATP mRNA expression, prevention of coronary heart disease has played therole of rapid arrhythmia.
引文
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