人参皂苷Re对异丙肾上腺素诱导离体灌流大鼠心脏心律失常的调节作用  

Effect of ginsenoside Re on isoproterenol-induced cardiac arrhythmia in isolated perfused rat heart

作　　者：曹瑀莹 杜丙秀 李劭恒 袁硕 陶雅军[1] 刘丽萍 陈颖卿 CAO Yu-ying;DU Bing-xiu;LI Shao-heng;YUAN Shuo;TAO Ya-jun;LIU Li-ping;CHEN Ying-qing(Dalian Key Laboratory of Chronic Disease Research Center,Dalian University,Dalian 116622,China;Yanbian University,Yanji 133022,China)

机构地区：[1]大连大学慢性病研究中心大连市重点实验室,辽宁大连116622 [2]延边大学,吉林延吉133022

出　　处：《中草药》2021年第20期6234-6244,共11页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(82000074);辽宁省自然科学基金指导计划项目(20180550388);辽宁省教育厅科学研究经费项目(jyt-dldxjc202005)。

摘　　要：目的探究人参皂苷Re对异丙肾上腺素(isoprenaline,ISO)诱导离体大鼠心脏心律失常的调节作用。方法提取原代乳鼠心肌细胞,通过CCK-8法检测人参皂苷Re对乳鼠心肌细胞存活率的影响。将雄性Wistar大鼠随机分为对照组、ISO组、人参皂苷Re+ISO组和人参皂苷Re组,通过Langendorff灌流系统对离体大鼠心脏进行给药,利用多电极阵列映射系统分析大鼠心肌电活动变化;通过苏木素-伊红(HE)染色观测离体大鼠心肌损伤情况;利用荧光共振能量转移成像系统实时监测心肌细胞内环磷酸腺苷(cyclic adenosine monophosphate,c AMP)和蛋白激酶A(protein kinase A,PKA)的含量变化;通过ELISA法检测各组离体心脏组织上清液中炎性因子水平。结果人参皂苷Re(1~50μmol/L)均对原代乳鼠心肌细胞的存活率无明显影响;与对照组相比,ISO组心室肌传导速度明显加快,传导方向变化显著,心率显著增高(P<0.05),心肌细胞脂肪变性严重程度增加,cAMP和PKA含量增加,趋化因子1(C-X-C motif chemokine 1,CXCL1)、CXCL2、CXCL3、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)水平均明显升高(P<0.05);与ISO组相比,人参皂苷Re+ISO组心率明显下降(P<0.05),心肌细胞脂肪变性严重程度减轻,c AMP和PKA含量降低,CXCL1、CXCL2、CXCL3、TNF-α和IL-6水平均显著降低(P<0.05)。结论人参皂苷Re可通过调节c AMP/PKA通路并抑制炎性反应干预快速型心律失常的发生。Objective To investigate the suppressive effect of ginsenoside Re on isoproterenol(ISO)-induced cardiac arrhythmia in isolated rat hearts. Methods CCK-8 assay was performed to assess the effect of ginsenoside Re on survival rate of primary neonatal ventricular myocytes isolated from rats. Male Wistar rats were randomly dived into control group, ISO group, ginsenoside Re + ISO group and ginsenoside Re group. Langendorff-perfused hearts were challenged with different drugs in turn, and the myocardial electrical activity was checked by multi-electrode array in isolated rat hearts. Myocardial injury in isolated rat hearts were detected by hematoxylin-eosin(HE) staining. Cyclic adenosine monophosphate(cAMP) and protein kinase A(PKA) contents were measured by targeted fluorescence resonance energy transfer probes in primary neonatal rat ventricular myocytes. Levels of inflammatory factors in isolated rat hearts were analyzed by ELISA. Results Ginsenoside Re(1—50 μmol/L) showed no significant effect on survival rate of primary neonatal rat ventricular myocytes. Compared with control group, ISO significantly changed the direction of conduction, increased the left ventricular conduction velocity and heart rate(P < 0.05);The severity of steatosis in heart tissues were significantly increased, cAMP and PKA contents were increased, C-X-C motif chemokine 1(CXCL1), CXCL2, CXCL3, tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) levels were significantly increased(P < 0.05). Compared with ISO group,ginsenoside Re + ISO group showed a significant decrease in heart rate, as well as in the severity of heart injury. cAMP and PKA contents were decreased, CXCL1, CXCL2, CXCL3, TNF-α and IL-6 levels were significantly decreased(P < 0.05). Conclusion Ginsenoside Re can ameliorate ISO-induced arrhythmia in isolated perfused rat hearts through regulating c AMP/PKA signaling pathway and inhibiting inflammatory factors expressions.

关 键 词：人参皂苷RE 心律失常 环磷酸腺苷 蛋白激酶A 炎性因子 

分 类 号：R285.5[医药卫生—中药学]