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

作　　者：汪晶晶[1] 王蔚然[1] 董颖[1] 李彬[1] 李洁[1] 白婧[1] 刘传斌 林琨[1] 陈韵岱[1] 李泱[1] WANG Jing-Jing;WANG Wei-Ran;DONG Ying;LI Bin;LI Jie;BAI Jing;LIU Chuan-Bin;LIN Kun;CHEN Yun-Dai;LI Yang(Department of Cardiology, First Medical Center, Chinese PLA General Hospital, Beijing 100853, China)

机构地区：[1]解放军总医院第一医学中心心血管内科,北京100853

出　　处：《中华老年多器官疾病杂志》2019年第5期365-371,共7页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：国家自然科学基金(N81870249)~~

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(200.0μmol/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(I_(ti),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)、I_(ti)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I_(ti)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�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(ICa,L) and sodium-calcium exchanger current(INCX)] in the 3 groups. Flou-4 AM 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,INCX and ICa,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 INCX 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 ICa,L from(-17.2+0.9) pA/pF to(-13.5+1.0) pA/pF(

关 键 词：大蒜素 心力衰竭 迟后除极 触发活动 离子流 

分 类 号：R541[医药卫生—心血管疾病]