甘草次酸对乌头碱致大鼠心律失常的拮抗作用

Antagonistic Effect of Glycyrrhetinic Acid Against Aconitine Induced Arrhythmia in Rats

目的:探究甘草次酸拮抗乌头碱致大鼠心律失常的作用机制。方法:将40只大鼠分成正常对照组、模型对照组、胺碘酮56 mg/kg组、甘草次酸50、150 mg/kg组,每组8只,以大鼠Ⅱ导联心电图变化为指标,动态观察用药后大鼠心电图和心率的变化,采用HE染色法评价心肌组织结构的改变,检测大鼠血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、脑钠肽(BNP)和心肌组织中Na^(+)-K^(+)-ATP酶,钙调蛋白(CaM)、钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)水平。结果:与正常对照组比较,模型对照组出现明显心率降低,BNP、LDH、CK水平明显升高,甘草次酸50、150 mg/kg组能有效恢复大鼠心率;BNP、 CK的释放显著降低(P<0.01),甘草次酸150 mg/kg组LDH含量明显降低(P<0.05);与正常对照组比较,模型对照组中Na^(+)-K^(+)-ATP酶水平明显降低、CaM和CaMKⅡ水平显著升高,甘草次酸150 mg/kg明显升高Na^(+)-K^(+)-ATP酶水平,降低CaM和CaMKⅡ水平(P<0.05)。HE染色结果表明,模型对照组心肌组织疏松,心肌细胞萎缩,排列紊乱,甘草次酸50 mg/kg组可见局部肌纤维坏死、变性,较模型对照组有好转。甘草次酸150 mg/kg组基本无炎症细胞浸润,心肌组织无坏死,变性明显好转,其他无明显病变。结论:甘草主要有效成分甘草次酸对乌头碱所致的大鼠心律失常具有较为明显的减毒作用。

Objective:To explore the antagonistic mechanism of glycyrrhetinic acid(GTA) against arrhythmia induced by aconitine in rats. Methods: Forty rats were divided into the normal control group, model group, 56 mg/kg amiodarone group, as well as 50 mg/kg and 150 mg/kg GTA groups, with eight rats in each group. Electrocardiogram(ECG) lead II features were recorded for dynamically monitoring the changes in rat ECG and heart rate after the treatment. Following the evaluation of changes in myocardial structure by HE staining, the levels of creatine kinase(CK), lactic dehydrogenase(LDH), and brain natriuretic peptide(BNP) in serum and Na^(+)-K^(+)-ATPase, CaM, calmodulin(CaMK), and calcium-calmodulin dependent protein kinase Ⅱ(CaMK Ⅱ) in rat myocardium were detected. Results: Compared with the normal control group, the model group exhibited significantly reduced heart rate, but increased BNP, LDH, and CK levels. However, GTA at 50 mg/kg and 150 mg/kg improved the heart rate and significantly decreased the release of BNP and CK(P<0.01). Besides, the LDH level significantly declined in the 150 mg/kg GTA group(P<0.05). Compared with the normal control group, the model group displayed significantly lowered Na^(+)-K^(+)-ATPase and elevated CaM and CaMK II. GTA at 150 mg/kg remarkably raised the Na^(+)-K^(+)-ATPase, but decreased the levels of CaM and CaMK II(P<0.05). HE staining results showed that the myocardial tissue was loosely arranged, with myocardial atrophy and cellular disorganization visible. In the 50 mg/kg GTA group, the local muscle fiber necrosis and degeneration were present, which were milder in comparison with the situations in the model group. In the 150 mg/kg GTA group, there was no inflammatory cell infiltration, necrosis, or other pathological changes in myocardial tissue. Conclusion: GTA, the main effective component in Gancao(甘草), is effective in reducing toxin in rats with arrhythmia induced by aconitine.