利福平对附子急性毒性物质诱导降解的研究
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摘要
目的:探究利福平对附子急性毒性物质的诱导降解效果。方法:建立附子诱导小鼠心律失常模型,通过分析心电图、血清乳酸脱氢酶同工酶1(lactate dehydrogenase isoenzyme,LDH1)活力和心肌组织切片比较不同浓度利福平诱导解毒的效果。结果:不同浓度的利福平溶液可以显著改善附子诱导的心脏损伤,部分逆转心动过速,减少心律失常的发生,降低心肌缺血发生率,抑制血浆心肌酶LDH1活性(P<0.001),组织病理切片结果提示利福平可以减轻口服生附片后心肌损伤坏死程度。结论:利福平作为肝药酶诱导剂可以显著减轻附子的急性毒性,该作用呈剂量依赖性。
Objective:To explore the effect of rifampicin on the induction of acute toxicity of Radix Aconiti Lateralis Preparata.Methods:The aconitine-induced arrhythmia model was established,then the effects of detoxification induced were compared by rifampicin via electrocardiogram,serum LDH1 activity and myocardial histopathological score.Results:Rifampicin in different concentration could significantly ameliorate heart damage compared with those use Radix Aconiti Lateralis Preparata only.The incidence of tachycardia and arrhythmias decreased partly,the incidence of myocardial ischemia also decreased,the activity of myocardial enzymes LDH1 was inhibited(P<0.001),and the histopathological results also suggest that rifampicin can reduce the degree of myocardial injury after oral administration of Radix Aconiti Lateralis Preparata.Conclusion:As a hepatic drug inducer,rifampicin can significantly reduce the acute toxicity of Radix Aconiti Lateralis Preparata,and the effect is dose-dependent.
Objective:To explore the effect of rifampicin on the induction of acute toxicity of Radix Aconiti Lateralis Preparata.Methods:The aconitine-induced arrhythmia model was established,then the effects of detoxification induced were compared by rifampicin via electrocardiogram,serum LDH1 activity and myocardial histopathological score.Results:Rifampicin in different concentration could significantly ameliorate heart damage compared with those use Radix Aconiti Lateralis Preparata only.The incidence of tachycardia and arrhythmias decreased partly,the incidence of myocardial ischemia also decreased,the activity of myocardial enzymes LDH1 was inhibited(P<0.001),and the histopathological results also suggest that rifampicin can reduce the degree of myocardial injury after oral administration of Radix Aconiti Lateralis Preparata.Conclusion:As a hepatic drug inducer,rifampicin can significantly reduce the acute toxicity of Radix Aconiti Lateralis Preparata,and the effect is dose-dependent.
引文
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[2] 张晶,孙桂波,雷崎方,等.生附片的化学成分研究[J].药学学报,2014,49(8):1150-1154.
[3] 周林,任玉珍,杜杰,等.附子不同炮制方法比较分析[J].中国现代中药,2013,15(2):135-139.
[4] 解素花,张广平,孙桂波,等.附子与甘草不同配伍比例配伍减毒的实验研究[J].中国中药杂志,2012,37(15):2210-2214.
[5] 王晓丽,李丽静,李玉梅,等.附子与人参不同配伍对心肌细胞的减毒作用[J].中国实验方剂学杂志,2015,21(11):153-158.
[6] 叶强,郭一平,彭成,等.附子无姜不热的成分研究[J].中成药,2013,30(5):1035-1039.
[7] 王龙虎,杜杰,周海燕,等.附子炮制研究进展[J].中国现代中药,2007,9(8):28-31,40.
[8] NYIRIMIGABO E,XU Y,LI Y,et al.A review on phytochemistry,pharmacology and toxicology studies of Aconitum[J].J Pharm Pharmacol,2015,67(1):1-19.
[9] CHAN T Y.Aconitum alkaloid poisoning related to the culinary uses of aconite roots[J].Toxins(Basel),2014,6(9):2605-2611.
[10] CHAN T Y.Aconitum alkaloid content and the high toxicity of aconite tincture[J].Forensic Sci Int,2012,222(1/3):1-3.
[11] 朱丽君.有毒乌头碱对CYP450酶的影响及其机制研究[D].广州:南方医科大学,2012.
[12] 张秋莹,刘芳,王雪峰,等.心炎宁颗粒剂对柯萨奇B3病毒所致病毒性心肌炎小鼠心肌病理改变和超微结构的影响[J].辽宁中医药大学学报,2012,14(3):83-85.
[13] 张硕峰.附子中三种双酯型生物碱的心脏毒效关系及甘草苷的干预作用[D].北京:北京中医药大学,2007.
[14] 梅超南,曾瑾,赵军宁.不同产地附子炮制品抗休克、抗缓慢型心律失常作用的品质评价研究[J].中药药理与临床,2014,30(1):67-70.
[15] 王懿,孙蓉.基于“回阳救逆”功效附子对小鼠心电图影响的“效—毒”关联评价[J].世界中医药,2014,9(2):155-158.
[16] FRIESE J,GLEITZ J,GUTSER U T,et al.Aconitum sp.alkaloids:the modulation of voltage-dependent Na+channels,toxicity and antinociceptive properties[J].Eur J Pharmacol,1997,337(2/3):165-174.
[17] 龚冬梅,邹晓龙,白云龙,等.哇巴因和乌头碱对豚鼠和大鼠心肌细胞钠电流的作用[J].哈尔滨医科大学学报,2006,40(5):347-350.
[18] 林津,徐红,徐文仪,等.重度乌头碱中毒心律失常的抢救体会[J].内科急危重症杂志,2002,8(4):219-220.