Protective Effect of Wenxin Granula on Heart from Myocardial Infarction through Regulating Intracellular Ca^(2+)

Objective To assess the anti-arrhythmic activity and cardioprotective effects of Wenxin Granula,a traditional Chinese formula(consisting of Salviae Miltiorrhizae Radix,Polygonati Rhizoma,Notoginseng Radix et Rhizoma,Nardostachyos Radix et Rhizoma,Angelicae Sinensis Radix,and Succinum),on heart in ischemic-induced myocardial infarction(MI) rats and compare with those of Amiodarone which have been demonstrated in clinic.Methods Rats were randomly divided into Sham-operated(control),MI + Amiodarone [5 mg/(kg.d)](MI),and MI + Wenxin Granula [10 mg/(kg.d)] groups and left anterior descending coronary artery was occluded in each group.After left anterior descending for 12 h,standard lead II of administration electrocardiogram was recorded in order to analyze the occurrence of arrhythmia.After one month,the size of the infarct area of heart was evaluated by TTC staining method and haemodynamic function was assessed to detect the heart function.Laser scanning confocal microscope and the technique of patch clamp were used to detect the intracellular Ca2+([Ca2+]i) and L-type calcium current(ICa-L),respectively.Results Both Wenxin Granula [10 mg/(kg.d)] and Amiodarone [5 mg/(kg.d)] could markedly decrease the incidence of arrhythmia in heart of rats which were subjected to ischemic injury.After one month,Wenxin Granula could significantly decrease mortality to 22.22% and reduce the infarct area(P < 0.05),but Amiodarone did not.The mechanism may involve that Wenxin Granula attenuated [Ca2+]i decreasing in MI rats.Additionally,Wenxin Granula could obviously ameliorate the impaired heart function of MI rats by decreasing the elevated left ventricular end-diastolic pressure and increasing the attenuated maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period.On the other hand,electrophysiological experiment results revealed that Wenxin Granula administration one month later also increased the reduced ICa-L density in rat ventricular myocytes in MI rats.The results of LSCM showed that Wenxin Granula could recover the amplitude of [Ca2+]i decreased by heart failure during long term.Conclusion Wenxin Granula could not only inhibit the incidence of arrhythmia but also decrease the mortality,which was accompanied by recovering the amplitude of [Ca2+]i.This protective effect of Wenxin Granula may partially be mediated through changing ICa-L as well as increasing [Ca2+]i.

稳心颗粒治疗扩张型心肌病室性心律失常的安全性及疗效观察

目的观察稳心颗粒治疗扩张型心肌病室性心律失常的临床疗效和安全性。方法扩张型心肌病室性心律失常46例在常规治疗的基础上,停用抗心律失常药物至少1周后,予稳心颗粒9g,每日3次温开水冲服,4周为1个疗程。结果显效率58.7%,总有效率89.1%。实验室检查(血、尿、粪常规,血脂,血糖,肝功能,肾功能)、心电图指标(心率、PR间期、QRS时限、QT间期)与用药前比较差异无统计学意义(P>0.05)。结论稳心颗粒治疗扩张型心肌病室性心律失常(主要是室性期前收缩)疗效显著,且无明显不良反应。

循经叩刺、温针灸足三里、悬钟联合稳心颗粒治疗急性脑血管疾病所致脑源性心律失常疗效及作用机制

目的观察循经叩刺、温针灸足三里、悬钟联合稳心颗粒治疗急性脑血管疾病所致脑源性心律失常的疗效及作用机制探讨。方法将126例急性脑血管疾病所致脑源性心律失常患者随机分为观察组64例及对照组62例,对照组给予西医常规治疗,观察组在对照组治疗基础上给予循经叩刺、温针灸足三里、悬钟联合稳心颗粒治疗,疗程为14 d;记录2组治疗期间不同时期心电图异常率的变化,观察2组治疗前后心律失常发生种类和发生率、相关生化指标、神经缺损评分的变化,随访3个月时预后情况。结果2组治疗3 d、5 d、7 d、14 d后的心电图异常率均显著降低(P均<0.05),观察组以上时间点的异常率均显著低于对照组(P均<0.05);2组治疗14 d后窦性心动过速、房性期前收缩、室性期前收缩、ST-T段改变、房室传导阻滞、阵发性室上速、室性心动过速发生率均较治疗前显著降低(P均<0.05),且观察组治疗14 d后窦性心动过速、房性期前收缩、室性期前收缩、ST-T段改变发生率均显著低于对照组(P均<0.05)。2组治疗后肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、天门冬氨酸氨基转移酶(AST)、肌红蛋白(MYO)、肌钙蛋白I(cTnI)、内皮素-1(ET-1)、去甲肾上腺素(NA)、肾上腺素(E)水平均较治疗前显著降低(P均<0.05),观察组治疗后以上指标水平均低于对照组(P均<0.05)。2组治疗后NO水平均较治疗前显著升高(P均<0.05),且观察组显著高于对照组(P<0.05)。2组治疗14 d后NIHSS评分均较治疗前显著降低(P均<0.05),且观察组显著低于对照组(P<0.05)。治疗后随访3个月,观察组mRS评分分级、预后良好率均显著优于对照组(P均<0.05)。结论循经叩刺、温针灸足三里、悬钟联合稳心颗粒可降低急性脑血管疾病所致脑源性心律失常的发生率,具有心血管与神经系统双重保护效应,其作用机制可能与改善血管内皮功能、抑制应激反应有关。

稳心颗粒对丙烯晴所致小鼠心肌毒性的影响

目的研究不同浓度丙烯腈(acrylonitrile,ACN)对小鼠的心肌毒性作用,并观察稳心颗粒对这种毒性作用的影响。方法选用50只8周龄健康雄性c57小鼠,按随机数字表法分为5组,ACN连续灌胃5 d,5组ACN浓度分别为0、2、4、8、16 mg/kg,7 d后通过小动物超声测量小鼠心脏左室内径和左室射血分数(LVEF),并取心脏组织,通过末端脱氧核苷酸转移酶荧光标记(terminaldeoxynucleoitidyl transferase mediated nick and labeling,TUNEL)和caspase3活性检测,分析心肌凋亡情况。再选用40只8周龄健康雄性c57小鼠,按随机数字表法分为4组:(1)对照组:灌胃PBS溶液5 d;(2)稳心颗粒组:灌胃稳心颗粒0.25 mg/kg 7 d;(3)ACN组:灌胃ACN 8 mg/kg 5 d;(4)ACN+稳心颗粒组:灌胃ACN 8 mg/kg 5 d后继续灌胃稳心颗粒0.25 mg/kg 7 d。7 d后测量各组小鼠心脏左室内径和LVEF,并取心脏组织,通过TUNEL和caspase3活性检测分析心肌凋亡情况。结果 4、8、16 mg/kg ACN能显著增大小鼠心脏左室内径,降低LVEF,显著增加心肌凋亡,且其毒性作用ACN与浓度有相关性。与ACN组相比,ACN+稳心颗粒组左室内径显著减小,LVEF显著升高,心肌凋亡以及组织中caspase3活性显著下降。结论 ACN能导致小鼠心肌毒性作用,且呈现剂量-效应关系。稳心颗粒能显著改善ACN的毒性作用。