【摘要】 目的:研究Na+通道阻滞剂河豚毒素(TTX)停搏液对离体大鼠心肌粘合连接的影响.方法:Wistar大鼠20只随机均分为TTX组和STH-2(St.Thomas-2)组,建立离体心脏Langendorff和Neely灌注模型,待搏动稳定,灌注30 min后停搏60 min,再灌注60 min,观察各组心脏停搏前后心率(HR)、冠状动脉流量(CAF)、左心室收缩末期压力(LVESP)以及压力变化速率(±dp/dt)的恢复率.采用免疫组化和WesternBlot检测大鼠心肌α肌动蛋白(α-actin)的分布和量的变化;免疫组化检测N型钙粘蛋白(N-cadherin)的分布及量的变化.结果:TTX组和STH-2组的停搏时间分别为(8.55±0.68)s和(9.49±0.49)s;复搏时间分别为(10.12±0.66)s和(10.88±0.61)s,与STH-2组比较,TTX组的停搏时间和复搏时间均明显缩短(P<0.01或P<0.05).复搏后,TTX组和STH-2组的HR,CAF,LVESP,+dp/dt及-dp/dt的恢复率分别为(85.65±1.98)%,(91.81±2.29)%,(85.03±0.91)%,(93.59±2.22)%,(92.87±2.59)%和(77.66±1.56)%,(88.28±1.81)%,(82.24±0.82)%,(90.25±3.31)%,(88.36±4.65)%,TTX组的各项血流动力学参数恢复率均优于STH-2组(P<0.01,P<0.05).免疫组化显示TTX组和STH-2组的N型钙粘蛋白和α肌动蛋白的表达量分别为0.06765±0.00027,0.07375±0.00049和0.02426±0.00025,0.03047±0.00017.Western Blot显示TTX组和STH-2组的α肌动蛋白的表达量分别为864.8±6.5,347.0±7.5.与TTX组比较,STH-2组分布紊乱,量明显减少(P<0.01).结论:以TTX阻断Na+通道为特点的心脏停搏液对大鼠心肌缺血-再灌注损伤时的粘合连接及心功能的保护作用优于STH-2心脏停搏液.更多还原

【Abstract】 AIM: To investigate the effects of cardioplegia with Na+ channel inhibitor tetrodotoxin(TTX) on myocardial adhesion junction of isolated rat hearts.METHODS: Langendorff and Neely perfusion models were steadily established,then the rat hearts(10 hearts in each group) were arrested by cardioplegia(St.Thomas No.2 solution,STH-2) in STH-2 group,and by cardioplegia(TTX) in TTX group respectively after perfusion for 30 min.These arrested hearts were remained for 60 min and then underwent reperfusion for 60 min.Pre and post-ischemia hemodynamic parameters of the rat hearts [heart rate(HR),carotid artery blood flow(CAF),left ventricular end systolic pressure(LVESP) and recovery rate of left ventricular pressure change speed] were studied and changes of myocardial N-cadherin were detected by immunohistochemistry and myocardial α-actin by Western Blot and immunohistochemistry.RESULTS: The arrest and recovery time were(8.55±0.68) s,(10.12±0.66) s in TTX group and(9.49±0.49) s,(10.88±0.61) s in STH-2 group.The arrest and recovery time were decreased remarkably in TTX group(P<0.01 or P<0.05),compared with STH-2 group.The recovery of myocardial hemodynamic parameters(HR,CAF,LVESP,+dp/dt,-dp/dt) during reperfusoin were(85.65±1.98)%,(91.81±2.29)%,(85.03±0.91)%,(93.59±2.22)%,(92.87±2.59)% in TTX group and(77.66±1.56)%,(88.28±1.81)%,(82.24±0.82)%,(90.25±3.31)%,(88.36±4.65)% in STH-2 group.There were no differences in myocardial hemodynamic parameters between the 2 groups before myocardial ischemia,but the recovery of myocardial hemodynamic parameters during reperfusoin in TTX group was better than that in STH-2 group(P<0.01 or P<0.05).Expression yields of myocardial N-cadherin and α-actin by immunohistochemistry were 0.06765±0.00027,0.07375±0.00049 in TTX group and 0.02426±0.00025,0.03047±0.00017 in STH-2 group.Expression yields of myocardial α-actin by Western Blotting were 864.8±6.5 in TTX group and 347.0±7.5 in STH-2 group.Distributions of myocardial N-cadherin and α-actin were disordered and their expressions were decreased significantly in STH-2 group(P<0.01).CONCLUSION: The protective effects of cardioplegia with Na+ channel inhibitor TTX on myocardial adhesion junction and myocardial hemodynamic parameters are better than those in STH-2 group during myocardial ischemia/reperfusion injuries on isolated rat hearts.更多还原