氧化苦参碱对大鼠急性心肌梗死诱发室性心律失常的影响

doi:10.3877/cma.j.issn.1674-0785.2020.11.013

目的

探讨氧化苦参碱（OMT）对急性心肌梗死（MI）大鼠诱发室性心律失常（VA）的影响及其可能机制。

方法

健康雄性SD大鼠75只，使用数字表法随机分为假手术组（Sham组）、MI组和OMT干预组（OMT组），每组25只。MI组和OMT组通过结扎冠状动脉左前降支建立MI模型，假手术组开胸但不结扎冠状动脉。OMT组在模型建立前2周及模型建立后2周连续给予OMT（100 mg/kg）灌胃处理。模型建立后2周，行心脏超声检查评估左心功能，酶联免疫吸附法检测血浆N-末端脑钠肽前体（NT-proBNP）和超敏肌钙蛋白T（hs-TnT）水平，分别使用RT-PCR和Western blotting检测心肌缝隙连接蛋白43（Cx43）mRNA和蛋白的表达，采用Burst刺激诱发VA。

结果

OMT组NT-proBNP、hs-TnT水平［（256.45±38.55）、（89.55±13.39）ng/L］与MI组［（371.93±41.23）、（132.63±20.12）ng/L］比较明显降低（P＜0.01）。Sham组、MI组与OMT组Cx43 mRNA相对表达量依次为0.93±0.16、0.47±0.06和0.71±0.12，3组Cx43蛋白相对表达量依次为0.77±0.11、0.50±0.07和0.61±0.08，3组p-Cx43蛋白相对表达量依次为0.62±0.09、0.32±0.05和0.50±0.07，差异均有统计学意义（P均＜0.05）。此外，OMT组与MI组比较VA诱发率明显降低（21.4% vs 64.3%，P＜0.05）。

结论

OMT可降低MI大鼠心肌的损伤和VA的发生率，其机制可能与OMT调整MI后心肌的Cx43表达有关。

关键词: 氧化苦参碱, 心肌梗死, 心律失常, 缝隙连接蛋白43

Objective

To investigate the effect of oxymatrine (OMT) on ventricular arrhythmia (VA) induced by myocardial infarction (MI) in rats and explore the possible mechanism.

Methods

Seventy-five healthy male SD rats were randomly divided into a sham operation group, an MI group, and an OMT intervention group, with 25 rats in each group. MI was induced by ligation of the left anterior descending coronary artery in the MI group and OMT group. OMT (100 mg/kg) was administered in the OMT group at two weeks before and two weeks after the establishment of the model. At the end of drug intervention, echocardiography was used to evaluate left ventricular function. The levels of NT-proBNP and hs-TnT in plasma were detected by ELISA. Cx43 mRNA and protein expression in the myocardium weas detected of by RT-PCR and Western blot, respectively. VA was induced by burst stimulation.

Results

The levels of NT-proBNP and hs-TnT in the OMT group were significantly lower than those in the MI group [(256.45±38.55) ng/L vs (371.93±41.23)ng/L, (89.55±13.39)ng/L vs (132.63±20.12)ng/L; P＜0.01]. The relative expression of Cx43 mRNA in the sham, MI, and OMT group was 0.93±0.16, 0.47±0.06 and 0.71±0.12 respectively, the relative expression of Cx43 protein in the three groups was 0.77±0.11, 0.50±0.07 and 0.61±0.08, respectively, and the relative expression of p-Cx43 protein was 0.62±0.09, 0.32±0.05 and 0.50±0.07 respectively; the differences among the three groups were statistically significant (P＜0.05 for all). In addition, the VA induction rate in the OMT group was significantly lower than that of the MI group (21.4% vs 64.3%, P＜0.05).

Conclusion

OMT can reduce the incidence of myocardial injury and VA in MI rats, and the underlying mechanism may be related to the regulation of Cx43 expression by OMT.

Key words: Oxymatrine, Myocardial infarction, Arrhythmia, Gap junction protein 43

表1 各组大鼠左心室超声相关指标比较（

x ˉ

±s）

组别	只数	LVEF	FS（%）	LPWD（mm）	LPWS（mm）	LVEDD（mm）	LVESD（mm）
Sham组	6	0.70±0.09	52.71±9.76	1.79±0.31	3.31±0.54	6.21±0.87	3.09±0.47
MI组	6	0.36±0.04^a	21.31±3.38^a	1.34±0.22^a	1.73±0.29^a	8.42±1.41^a	6.51±0.83^a
OMT组	6	0.45±0.07^ab	31.86±5.38^ab	1.54±0.25^ab	2.32±0.40^ab	7.09±1.25^ab	5.02±0.69^ab
F值		17.341	19.452	8.345	11.359	7.982	14.224
P值		＜0.01	＜0.01	＜0.01	＜0.01	＜0.01	＜0.01

表1 各组大鼠左心室超声相关指标比较（

x ˉ

±s）

组别	只数	LVEF	FS（%）	LPWD（mm）	LPWS（mm）	LVEDD（mm）	LVESD（mm）
Sham组	6	0.70±0.09	52.71±9.76	1.79±0.31	3.31±0.54	6.21±0.87	3.09±0.47
MI组	6	0.36±0.04^a	21.31±3.38^a	1.34±0.22^a	1.73±0.29^a	8.42±1.41^a	6.51±0.83^a
OMT组	6	0.45±0.07^ab	31.86±5.38^ab	1.54±0.25^ab	2.32±0.40^ab	7.09±1.25^ab	5.02±0.69^ab
F值		17.341	19.452	8.345	11.359	7.982	14.224
P值		＜0.01	＜0.01	＜0.01	＜0.01	＜0.01	＜0.01

表2 各组NT-proBNP、hs-TnT水平比较（ng/L，

x ˉ

±s）

组别	只数	NT-proBNP	hs-TnT
Sham组	6	137.41±19.22	46.96±8.78
MI组	6	371.93±41.23^a	132.63±20.12^a
OMT组	6	256.45±38.55^ab	89.55±13.39^ab
F值		21.132	19.562
P值		＜0.01	＜0.01

表2 各组NT-proBNP、hs-TnT水平比较（ng/L，

x ˉ

±s）

组别	只数	NT-proBNP	hs-TnT
Sham组	6	137.41±19.22	46.96±8.78
MI组	6	371.93±41.23^a	132.63±20.12^a
OMT组	6	256.45±38.55^ab	89.55±13.39^ab
F值		21.132	19.562
P值		＜0.01	＜0.01

图1 各组Cx43、p-Cx43蛋白表达情况

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Effect of oxymatrine on ventricular arrhythmia induced by acute myocardial infarction in rats

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Effect of oxymatrine on ventricular arrhythmia induced by acute myocardial infarction in rats