异甘草素对心肌梗死大鼠诱导的室性心律失常及炎症因子的影响

Effect ofisoliquiritigenin on ventricular arrhythmia and inflammatory factors induced by myocardial infarction rats

目的研究异甘草素(isoliquiritigenin,ISL)对心肌梗死(myocardial infarction,MI)大鼠诱导的室性心律失常及炎症因子的影响。方法无特定病原体动物(specific pathogen free,SPF)级雄性SD大鼠40只,随机分为正常组,模型组,ISL低剂量组,ISL中剂量组和ISL高剂量组五组,每组8只,后四组结扎左冠状动脉前降支建立MI模型。4周后第2天至第5天,用超声测量大鼠左室射血分数(left ventricular ejection fraction,LVEF)、左室短轴缩短率(left ventricular short-axis shorting rate,LVFS)、左室收缩未期内径(left ventricular contractile median diameter,LVIDS)、左室舒张未期内径(left ventricular diastolic median diameter,LVID)。利用体表心电图记录和测量心率(heart rate,HR)、PR间期、QRS波时限和QTc间期。在Burst刺激心室诱发心律失常前30 min,ISL低、中、高剂量组大鼠尾静脉注射ISL(25、50、100 mg/L),正常组和模型组大鼠均以相同的给药方式给予等量的生理盐水。记录6、8、10 V Burst刺激下室性心律失常的持续时间。实验完成后,采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测大鼠血清中C反应蛋白(C-reactive protein,CRP)、白细胞介素(interleukin,IL)-6、脑钠肽(brain natriuretic peptide,BNP)。结果与正常组相比,模型组、ISL低、中、高剂量组心脏超声指标LVIDS及LVIDD均明显升高,LVEF、LVFS明显降低,差异具有统计学意义(F=10.28、15.57、19.03、16.39,P值均<0.05);与ISL低、中剂量组相比,ISL高剂量组LVEF、LVFS明显升高,LVIDS、LVIDD明显降低,差异具有统计学意义[%:(0.50±0.08)或(0.52±0.06)比(0.53±0.07),%:(0.21±0.05)或(0.22±0.06)比(0.23±0.06),mm:(6.11±0.83)或(6.09±0.79)比(6.04±0.82),mm:(7.79±0.82)或(7.76±0.74)比(7.72±0.58),P=0.02、0.04、0.01、0.02]。与正常组、模型组相比,ISL低、中、高剂量组体表心电图指标HR及QRS波时限均明显升高,PR及QTc间期明显降低,差异有统计学意义(F=17.16、19.82、21.68、16.96,P值均<0.05);与ISL低、中剂量组相比,ISL高剂量组的HR明显降低,QTc间期明显升高,差异有统计学意义[次/分:(320±19)或(312±28)比(297±30),ms:(89.95±21.58)或(96.75±20.16)比(104.36±19.24),P=0.01、0.00],而PR间期和QRS波时限差异没有统计学意义(P>0.05)。与模型组比较,ISL低、中、高剂量组大鼠6、8、10 V室性心律失常的持续时间明显降低,差异具有统计学意义(F=22.68、12.14、17.82,P值均<0.05);与ISL低、中剂量组相比,ISL高剂量组大鼠室性心律失常的持续时间明显降低,差异具有统计学意义[s:(4.59±1.84)或(4.12±1.75)比(3.28±1.68),(5.97±4.04)或(5.36±3.85)比(4.06±3.28),(10.07±9.84)或(9.05±9.21)比(8.26±8.05),P=0.01、0.00、0.02]。与正常组、模型组比较,ISL低、中、高剂量组大鼠CRP、IL-6、BNP含量均显著降低,差异具有统计学意义(F=11.48、26.11、15.24,P值均<0.05);与ISL低、中剂量组相比,ISL高剂量组大鼠CRP、IL-6和BNP含量明显降低,差异具有统计学意义[mg/L:(3.01±0.42)或(2.78±0.41)比(2.43±0.32),pg/mL:(105.84±13.28)或(98.05±12.35)比(92.19±8.74),pg/mL:(15.96±1.24)或(14.63±1.35)比(13.53±1.26),P=0.01、0.02、0.02]。结论ISL可以降低MI大鼠诱发室性心律失常的持续时间,降低血清炎性因子CRP、IL-6、血清中BNP的含量。

Objective To study the effects of isoliquiritigenin on ventricular arrhythmias and inflammatory cytokines induced by myocardial infarction(MI)in rats.Methods Forty specific pathogen free(SPF)male SD rats were randomly divided into five groups:normal group,model group,isoliquiritigenin low-dose group,isoliquiritigenin medium-dose group and isoliquiritigenin high-dose group,with 8 rats in each group.The MI model was established by ligation of the left anterior descending coronary artery in the last four groups.From days 2 to days 5 after 4 weeks,left ventricular ejection fraction(LVEF),left ventricular short-axis shorting rate(LVFS),left ventricular contractile median diameter(LVIDS)and left ventricular diastolic median diameter(LVID)were measured by ultrasound.Heart rate(HR),PR interval,QRS duration,and QTc interval were recorded and measured using body surface electrocardiogram.At 30 min before bursting ventricle stimulation induced arrhythmia,isoliquiritigenin low-dose,isoliquiritigenin medium-dose and isoliquiritigenin high-dose groups were intravenously injected with isoliquiritigenin(25,50 and 100 mg/L),and normal group and model group were all given the same amount of normal saline in the same way.Duration of ventricular arrhythmias under 6,8,10 V Burst stimulation was recorded.After the experiment,the serum levels of C-reactive protein(CRP),interleukin-6(IL-6)and brain natriuretic peptide(BNP)were determined by enzym-linked immunosorbent assay(ELISA).Results Compared with the normal group,the cardiac ultrasound indexes LVIDS and LVIDD in model group,ISL low-dose,medium-dose and high-dose groups were significantly increased,while LVEF and LVFS were significantly decreased(F=10.28,15.57,19.03,16.39,all P values<0.05).Compared with low and medium dose ISL groups,LVEF and LVFS were significantly increased,while LVIDS and LVIDD were significantly decreased in high dose ISL group[%:(0.50±0.08)or(0.52±0.06)vs(0.53±0.07),%:(0.21±0.05)or(0.22±0.06)vs(0.23±0.06),mm:(6.11±0.83)or(6.09±0.79)vs(6.04±0.82),mm:(7.79±0.82)or(7.76±0.74)vs(7.72±0.58),P=0.02,0.04,0.01,0.02].Compared with normal group and model group,HR and QRS duration of body surface ECG were significantly increased,while PR and QTc interval were significantly decreased in low-dose,medium-dose and high-dose ISL groups(F=17.16,19.82,21.68,16.96,all P values<0.05).Compared with low-dose and medium-dose ISL groups,HR in high-dose ISL group was significantly decreased,and QTc interphase was significantly increased[n/m:(320±19)or(312±28)vs(297±30),ms:(89.95±21.58)or(96.75±20.16)vs(104.36±19.24),P=0.01,0.00],while there was no significant difference between PR interval and QRS duration(P>0.05).Compared with model group,the duration of ventricular arrhythmia in with 6,8,10 V in low-dose,medium-dose and high-dose ISL groups was significantly reduced(F=22.68,12.14,17.82,all P values<0.05).Compared with low and medium dose ISL groups,the duration of ventricular arrhythmia in high dose ISL group was significantly reduced[s:(4.59±1.84)or(4.12±1.75)vs(3.28±1.68),(5.97±4.04)or(5.36±3.85)vs(4.06±3.28),(10.07±9.84)or(9.05±9.21)vs(8.26±8.05),P=0.01,0.00,0.02].Compared with normal group and model group,the contents of CRP,IL-6 and BNP in low-dose,medium-dose and high-dose ISL groups were significantly decreased(F=11.48,26.11,15.24,all P values<0.05).Compared with low-dose and medium-dose ISL groups,the contents of CRP,IL-6 and BNP in high-dose ISL group were significantly decreased[mg/L:(3.01±0.42)or(2.78±0.41)vs(2.43±0.32),pg/mL:(105.84±13.28)or(98.05±12.35)vs(92.19±8.74),pg/mL:(15.96±1.24)or(14.63±1.35)vs(13.53±1.26),P=0.01,0.02,0.02].Conclusions Isoliquiritigenin can reduce the duration of ventricular arrhythmias induced by myocardial infarction in rats,and reduce the contents of serum inflammatory factors CRP,IL-6 and BNP.