基于钙超载研究滇乌碱诱导大鼠心律失常的毒性机制
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篇名: 基于钙超载研究滇乌碱诱导大鼠心律失常的毒性机制
TITLE: Study on the Toxicity Mechanism of Yunaconitine-induced Arrhythmia in Rats Based on Calcium Overload
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、0.14mg/kg)和乌头碱组(阳性对照,0.88mg/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7d。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、心肌细胞中Ca2+含量、心肌组织中Na+-K+-ATP酶和Ca2+-Mg2+-ATP酶活性以及雷诺定受体2(RyR2)、Ca2+-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Ca2+含量显著升高(P<0.05),心肌组织中ATP含量、Ca2+-Mg2+-ATP酶活性、Na+-K+-ATP酶活性和SERCA2蛋白表达水平均显著降低(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Ca2+含量均显著升高(P<0.01),心肌组织中ATP含量、Ca2+-Mg2+-ATP酶活性、Na+-K+-ATP酶活性和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Ca2+-Mg2+-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Ca2+超载有关。
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 2+ in myocardial cells ,the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase as well as the protein expression of ranolidine receptor 2(RyR2)and Ca 2+-ATPase(SERCA2)in myocardial tissue were determined. 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 Ca2+-Mg2+-ATPase and Na +-K+-ATPase as well as the protein expression of SERCA 2 in myocardial tissue were reduced significantly (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 2+-Mg2+-ATPase and Na +-K+-ATPase,and protein expression of RyR 2 and SERCA 2 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 reducing the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase and down-regulating the expression of related calcium transporter RyR2 and SERCA 2.
期刊: 2021年第32卷第23期
作者: 张祉思,程婉秋,江涛,沈志滨,陈艳芬,陈聪,司徒莹,唐春萍
AUTHORS: ZHANG Zhisi, CHENG Wanqiu,JIANG Tao,SHEN Zhibin,CHEN Yanfen,CHEN Cong,SITU Ying,TANG Chunping
关键字: 滇乌碱;心律失常;钙超载;腺苷三磷酸;雷诺定受体2;Ca2+-ATP酶;毒性机制
KEYWORDS: Yunaconitine;Arrhythmia;Calcium overload ;
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