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中国人民解放军总医院老年心血管病研究所
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中华老年多器官疾病杂志编辑委员会
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创刊人 王士雯
总编辑 范利
副总编辑 陈韵岱
执行主编 叶大训
编辑部主任 王雪萍
ISSN 1671-5403
CN 11-4786
创刊时间 2002年
出版周期 月刊
邮发代号 82-408
友情链接
汪晶晶,王蔚然,董颖,李彬,李洁,白婧,刘传斌,林琨,陈韵岱,李泱.大蒜素对大鼠心力衰竭模型心室肌细胞迟后除极和触发活动的作用[J].中华老年多器官疾病杂志,2019,18(5):365~371
大蒜素对大鼠心力衰竭模型心室肌细胞迟后除极和触发活动的作用
Effect of allicin on delayed afterdepolarization and triggered activity in ventricular myocytes of rats with heart failure
投稿时间:2019-01-09  
DOI:10.11915/j.issn.1671-5403.2019.05.075
中文关键词:  大蒜素;心力衰竭;迟后除极;触发活动;离子流
英文关键词:allicin; heart failure; delayed afterdepolarization; triggered activity; ion currents This work was supported by National Natural Science Foundation of China
基金项目:国家自然科学基金(N81870249)
作者单位E-mail
汪晶晶 解放军总医院第一医学中心心血管内科,北京 100853  
王蔚然 解放军总医院第一医学中心心血管内科,北京 100853  
董颖 解放军总医院第一医学中心心血管内科,北京 100853  
李彬 解放军总医院第一医学中心心血管内科,北京 100853  
李洁 解放军总医院第一医学中心心血管内科,北京 100853  
白婧 解放军总医院第一医学中心心血管内科,北京 100853  
刘传斌 解放军总医院第一医学中心心血管内科,北京 100853  
林琨 解放军总医院第一医学中心心血管内科,北京 100853  
陈韵岱 解放军总医院第一医学中心心血管内科,北京 100853  
李泱 解放军总医院第一医学中心心血管内科,北京 100853 liyangbsh@163.com 
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中文摘要:
      目的 观察大蒜素对大鼠心力衰竭模型细胞迟后除极(DAD)、触发活动(TA)和离子流的作用及机制。方法 选取20只SD大鼠利用腹主动脉结扎法制备大鼠心力衰竭模型(模型组),另选取10只SD大鼠制作假手术组作为对照。采用酶解法急性分离2组大鼠心室肌细胞。根据实验设计对模型组是否给以大蒜素干预分为心力衰竭组(未给药)及给药组(200.0 μmol/L大蒜素)。膜片钳技术观察心力衰竭组、给药组及对照组细胞DAD和TA的发生,并记录相关离子流(Iti, ICa,L,INCX)的改变,以Flou-4AM荧光技术检测细胞内钙离子浓度变化。采用SPSS 17.0软件进行统计学分析。组间比较采用ANOVA分析及SNK-q检验。结果 (1)对照组、心力衰竭组及给药组细胞上DAD和TA发生率依次为[13.3%(2/15),0.0%(0/15)]、[60.0%(9/15),26.7%(4/15)]和[40.0%(6/15),13.3%(2/15)]。与对照组比较,心力衰竭组细胞DAD和TA发生率显著增加;与心力衰竭组比较,给药组细胞上DAD和TA发生率显著下降,下降幅度分别为20.0%和13.4%,差异均有统计学意义(n=15,P<0.01)。(2)与对照组比较,心力衰竭组心室肌细胞上ICa,L、Iti和INCX电流密度均增加,而与心力衰竭组比较,给药组上述电流均减少,其中Iti内向峰电流密度从(-1.05±0.06)pA/pF降至(-0.53±0.05)pA/pF(n=10,P<0.01),INCX内向电流密度从(-5.8±0.7)pA/pF降至(-4.2±0.4)pA/pF(n=10,P<0.01)。同时,给药组通过大蒜素加速通道电流的稳态失活过程,降低ICa,L,ICa,L的峰电流密度由(-17.2±0.9)pA/pF降为(-13.5±1.0)pA/pF(n=15,P<0.01)。(3)与对照组比较,心力衰竭组细胞静息态钙浓度、钙瞬变幅度和胞内钙最高50%的时间等参数显著升高;与心力衰竭组比较,上述参数在给药组细胞中均显著降低(n=15,P<0.01)。心力衰竭组细胞内钙瞬变衰减率与对照组比较显著下降,而应用大蒜素后,得到显著恢复(P<0.05)。结论 大蒜素可能通过减少心力衰竭大鼠心室肌细胞内的钙离子,阻滞Iti和INCX电流,从而降低心力衰竭后DAD和TA的发生。
英文摘要:
      Objective To investigate the effect of allicin (All) on the delayed afterdepolarization (DAD), triggered activity (TA) and ion currents in the ventricular myocytes of rats with heart failure and the related mechanism. Methods Heart failure models were established in 20 SD rats by abdominal aortic ligation, and sham operation was performed in 10 SD rats as control. Enzymic digestion was used to isolate ventricular myocytes in the 2 groups. According to the experimental design, the model cells were divided into heart failure group (without administration, HF) and administration group (200.0 μmol/L All, HF+All). Patch clamp technique was used to observe the occurrence of DAD and TA and to record the associated changes of ion currents [the transient inward current (Iti), L-type calcium current (ICa,L) and sodium-calcium exchanger current (INCX)] in the 3 groups. Flou-4AM fluorescence technique was used to detect the changes of intracellular calcium concentration. SPSS statistics 17.0 was used for statistical analysis. ANOVA and SNK-q test were used for comparison among groups. Results (1)The incidences of DAD and TA in the control group, HF group and HF+All group were [13.3%(2/15), 0.0%(0/15)], [60.0%(9/15), 26.7%(4/15)] and [40.0%(6/15), 13.3%(2/15)] respectively. Compared with the control group, the incidences of DAD and TA in the HF group increased significantly. Compared with the HF group, the incidences of DAD and TA in the HF+All group decreased significantly by 20.0% and 13.4% respectively (n=15, P<0.01). (2) Compared with control group, Iti,INCX and ICa,L density increased in the HF group, but compared withHF group, they decreased in the HF+All group, in which Iti peak inward current density decreased from(-1.05±0.06)pA/pF to(-0.53±0.05)pA/pF (n=10, P<0.01) and INCX inward current density from (-5.8±0.7)pA/pF to (-4.2±0.4)pA/pF (n=10, P<0.01). At the same time, All accelerated the steady-state inactivation of channel currents and decreased the peak current density of ICa,L from (-17.2+0.9) pA/pF to (-13.5+1.0) pA/pF (n=15, P<0.01). (3) Compared with the control group, the resting calcium concentration, transient calcium amplitude and time for intracellular calcium concentrations to reach 50% of maximum value in the HF group were significantly higher, but those parameters were significantly lower in the HF+All group than in the HF group (n=15, P<0.01). The intracellular calcium transient attenuation rate in the HF group was significantly lower than that in the control group, but it recovered significantly after the application of All (P<0.05). Conclusion All may reduce the occurrence of DAD and TA by reducing intracellular calcium and blocking Iti and INCX currents in ventricular myocytes of rats with heart failure.
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