Page 44 - 《中国药房》2021年23期

基于钙超载研究滇乌碱诱导大鼠心律失常的毒性机制 Δ

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张祉思 ，程婉秋 ，江 涛 ，沈志滨 ，陈艳芬 ，陈 聪 ，司徒莹 ，唐春萍 （1.广东药科大学中药学院，广州
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510006；2.广东药科大学实验动物中心，广州 510006；3.广东省局部精准药物递药制剂工程技术研究中心，广州
510006）
中图分类号 R285 文献标志码 A 文章编号 1001-0408（2021）23-2854-05
DOI 10.6039/j.issn.1001-0408.2021.23.07
摘 要 目的：研究滇乌碱诱导大鼠心律失常的毒性机制。方法：将32只大鼠按随机数字表法随机分为正常对照组，滇乌碱低、
高剂量组（0.09、0.14 mg/kg）和乌头碱组（阳性对照，0.88 mg/kg），每组8只。各给药组大鼠每天灌胃相应药物1次，正常对照组大
鼠灌胃等体积生理盐水，连续7 d。末次灌胃后，观察各组大鼠的心电图变化，测定大鼠心肌组织中腺苷三磷酸（ATP）含量、心肌
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细胞中Ca 含量、心肌组织中Na -K -ATP酶和Ca -Mg -ATP酶活性以及雷诺定受体2（RyR2）、Ca -ATP酶（SERCA2）蛋白表达水
平。结果：与正常对照组比较，滇乌碱低剂量组大鼠QRS波时限、校正后QT期间（QTc间期）均显著延长（P＜0.01），心肌细胞中
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Ca 含量显著升高（P＜0.05），心肌组织中ATP含量、Ca -Mg -ATP酶活性、Na -K -ATP酶活性和SERCA2蛋白表达水平均显著降
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低（P＜0.05或P＜0.01）；滇乌碱高剂量组和乌头碱组大鼠心率均显著增快（P＜0.05或P＜0.01），QRS波时限、QTc间期均显著延
长（P＜0.01），心肌细胞中 Ca 含量均显著升高（P＜0.01），心肌组织中 ATP 含量、Ca -Mg -ATP 酶活性、Na -K -ATP 酶活性和
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RyR2、SERCA2 蛋白表达水平均显著降低（P＜0.01）。结论：滇乌碱可导致大鼠心律失常；其作用机制可能与降低心肌组织中
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Ca -Mg -ATP酶、Na -K -ATP酶活性，下调心肌组织中钙转运相关蛋白RyR2、SERCA2的表达，从而导致Ca 超载有关。
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关键词 滇乌碱；心律失常；钙超载；腺苷三磷酸；雷诺定受体2；Ca -ATP酶；毒性机制
Study on the Toxicity Mechanism of Yunaconitine-induced Arrhythmia in Rats Based on Calcium Overload
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ZHANG Zhisi ，CHENG Wanqiu ，JIANG Tao ，SHEN Zhibin ，CHEN Yanfen ，CHEN Cong ，SITU Ying ，TANG
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Chunping （1.School of Traditional Chinese Medicine，Guangdong Pharmaceutical University，Guangzhou
510006，China；2. Laboratory Animal Center，Guangdong Pharmaceutical University，Guangzhou 510006，
China；3. Guangdong Engineering Research Center for Local Precise Drug Delivery，Guangzhou 510006，China）
ABSTRACT OBJECTIVE：To study the toxicity mechanism of yunacotine-induced arrhythmia in rats. METHODS：Totally 32
rats were randomly divided by random number table method into normal control group，yunacotine low-dose and high-dose groups
（0.09，0.14 mg/kg），aconitine group（positive control，0.88 mg/kg），with 8 rats in each group. Administration groups were given
the corresponding drugs once a day，and normal control group was given the constant volume of normal saline，for consecutive 7 d.
After last intragastric administration， the changes of electrocardiogram （ECG） were observed. The contents of adenosine
triphosphate（ATP）in myocardial tissue and Ca in myocardial cells，the activities of Na -K -ATPase and Ca -Mg -ATPase as well
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as the protein expression of ranolidine receptor 2 （RyR2） and Ca -ATPase （SERCA2） in myocardial tissue were determined.
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RESULTS：Compared with normal control group，time limit of QRS wave and QTc intervals of rats were prolonged significantly in
yunaconitine low-dose group （P＜0.01）. The content of Ca 2 + in myocardial cells， the ATP contents， the activities of
Ca -Mg -ATPase and Na -K -ATPase as well as the protein expression of SERCA2 in myocardial tissue were reduced significantly
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（P＜0.05 or P＜0.01）. The heart rate of rats in yunaconitine high-dose group and aconitine group were increased significantly（P＜
0.05 or P＜0.01），and time limit of QRS wave and QTc intervals were significantly prolonged（P＜0.01）；the content of Ca 2+ in
myocardial cells was increased significantly（P＜0.01）；ATP content，the activities of Ca -Mg -ATPase and Na -K -ATPase，and
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protein expression of RyR2 and SERCA2 in myocardial tissue were decreased significantly （P＜0.01）. CONCLUSIONS：
Yunaconitine can induce arrhythmia in rats，the mechanism of which may be associated with Ca 2 + overload that resulted from
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reducing the activities of Na -K -ATPase and Ca -Mg -ATPase and down-regulating the expression of related calcium transporter
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RyR2 and SERCA2.
Δ 基金项目：国家中医药行业科研专项（No.201507004）
KEYWORDS Yunaconitine；Arrhythmia；Calcium overload；
＊硕士研究生。研究方向：中药药效评价与临床应用。E-mail：
2737911514@qq.com Adenosine triphosphate；Ryanodine receptor 2；Ca 2 + ATPase；
# 通信作者：教授，硕士生导师。研究方向：中药药效评价与临床 Toxicity mechanism
应用。E-mail：tchp66@163.com
·2854 · China Pharmacy 2021 Vol. 32 No. 23 中国药房 2021年第32卷第23期