黄连素通过保护肠道黏膜屏障缓解阿霉素诱导的心肌毒性的研究  

Berberine alleviates doxorubicin-induced cardiotoxicity by protecting the intestinal mucosal barrier

作　　者：朱续昌 邵宏安 周小扣 肖珺文 刘文涛[2] 金莱 李庆国[1] ZHU Xu-chang;SHAO Hong-an;ZHOU Xiao-kou;XIAO Jun-wen;LIU Wen-tao;JIN Lai;LI Qing-guo(Cardiovascular Center,Second Affiliated Hospital of Nanjing Medical University,Nanjing 210009,China;Jiangsu Key Laboratory of Neurodegeneration,Department of Pharmacology,Nanjing Medical University,Nanjing 210009,China)

机构地区：[1]南京医科大学第二附属医院心血管中心,江苏省南京市210009 [2]南京医科大学药理学系,江苏省神经变性重点实验室,江苏省南京市

出　　处：《中国心血管病研究》2023年第5期434-439,共6页Chinese Journal of Cardiovascular Research

基　　金：国家自然科学基金(82170503);江苏省重点研发计划(社会发展)项目(BE2021749)。

摘　　要：目的探究黄连素是否在阿霉素(doxorubicin,Dox)诱导的心肌毒性发挥心脏保护作用及其潜在机制。方法将30只小鼠随机分为对照组(Control组),模型组(Dox组),治疗组(Dox+BBR,200 mg/kg组)。监测小鼠化疗后的病死率,全自动生化分析仪检测小鼠血清中肌酸激酶同工酶(CK-MB),肌钙蛋白(cTnl)的含量;超声心动图评价小鼠心功能。心电图检测小鼠心率,检测小鼠心电QRS波时程、QT间期。彩色激光多普勒检测小鼠肠道血流,Elisa检测小鼠血清中脂多糖(Lipopolysaccharide,LPS)的变化。黄连素治疗结束后,苏木素-伊红(HE)染色观察细胞形态与结构。Western blot检测心脏中组织因子(Tissue factor,TF)、组织因子途径抑制物(Tissue factor pathway inhibitor,TFPI)、基质金属蛋白酶-9(Matrix metalloproteinase,MMP-9)及凋亡相关蛋白Bax、Bcl-2的表达。结果黄连素降低了阿霉素诱导小鼠的死亡率,改善了心脏挛缩,显着抑制了血清中心肌损伤标志物的水平。心电图结果显示,黄连素缓解了心脏传导系统的异常。Dox+BBR组肠道微循环血流量高于Dox组。相比之下,Dox+BBR组血清中LPS水平较低(P<0.05)。与对照组相比,TF、MMP-9和Bax的表达水平显著降低(P<0.05),而TFPI和Bcl-2在心脏中的表达水平显著升高(P<0.05)。结论黄连素通过改善肠道黏膜屏障功能,减少内毒素入血,抑制心脏中TF的表达和炎症的产生,发挥心脏保护功能。Objective To investigate whether berberine plays a cardiac protective role in Doxorubicin(Dox)induced myocardial toxicity and its potential mechanism.Methods A totle of 30 mice were randomly assigned to 3 groups as follows:the saline group,Dox group and Dox+BBR(200 mg/kg)group.The mortality of mice after chemotherapy was monitored.The cardiac function of the mice were evaluated and the change of CK-MB,cTnl in the mice serum were detected.ECG was used to monitor the heart rate,QRS wave and QT interval.The intestinal blood flow was detected by color laser Doppler and the level of LPS in serum were detected by Elisa.Moreover,HE staining was performed to observe cell morphology and structure.Western blot was used to determine the expression of TF,TFPI,MMP-9,Bax and Bcl-2 in the heart.Results Berberine decreased the mortality of DOX-induced mice,improved cardiac contracture,inhibited the level of myocardial injury markers in serum noticeably.The results of ECG showed that Berberine alleviated the abnormal cardiac conduction system.Intestinal microcirculation blood flow in the Dox+BBR group was higher than that in the Dox group.In contrast,the level of LPS in serum was lower in the Dox+BBR group(P<0.05).Compared with the Control group,the expression level of TF,MMP-9 and Bax were significantly decreased(P<0.05),while the level of TFPI and Bcl-2 in the heart were significantly increased(P<0.05).Conclusion Berberine can improve intestinal mucosal barrier function,reduce endotoxin into blood,inhibit TF expression and inflammation in the heart,then exert cardiac protective effect.

关 键 词：阿霉素 肠道 内毒素 黄连素 

分 类 号：Q95-33[生物学—动物学] R54[医药卫生—心血管疾病]