板芪口服液急性毒性及长期毒性试验研究
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摘要
探讨新兽药板芪口服液的急性毒性与长期毒性,评价其安全性。小鼠灌服板芪口服液进行急性毒性预试验,未获得动物的半数致死量,遂以最大给药剂量(270 g生药·kg~(-1)体重)进行急性毒性试验。将80只大鼠随机分为板芪口服液低、中、高剂量组和空白对照组,每组20只,雌雄各半,进行长期毒性试验。分别以10 g生药·kg~(-1)体重(猪临床推荐剂量的20倍)、20 g生药·kg~(-1)体重(猪临床推荐剂量的40倍)、40 g生药·kg~(-1)体重(猪临床推荐剂量的80倍)给大鼠灌服,对照组灌服等体积蒸馏水,给药容积为1 m L·100 g~(-1)体重,每天1次,连续给药30 d,期间观察大鼠外观体征及行为活动。停止给药24 h和15 d后进行剖检、血液生化检查和病理组织切片观察。结果显示,板芪口服液急性毒性试验评价为无毒,长期毒性试验中各剂量组大鼠的观察指标和测定指标与空白对照组相比均无显著差异,表明板芪口服液安全无毒,可用于临床试验。
To investigate the acute and chronic toxicity as well as to evaluate the safety level of Banqi( oral liquid). For acute pre toxicity test,performed at the maximum dose( 270 g/kg) of Banqi were drench to the mice.For chronic toxicity,based and compared to the dose of Banqi( oral liquid) used in pigs,we randomly and equally divided 80 rats into 4 groups into 4 groups( half male and half female),the low-dose( 20 times of pig dose i.e.10 g/kg),medium-dose( 40 times i. e. 20 g/kg),high-dose( 80 times dose i. e. 40 g/kg) and the control group( equal volume of water). 1 m L·100 g~(-1) body weight of Banqi was drenched once a day for 30 days.The clinical signs and behavioral activities of the rats were observed during this period. At 24 h and at 15 d of Banqi oral liquid cessation,body weight,hematology,blood biochemistry and histopathology were performed. The Acute toxicity test showed that Banqi( oral liquid) is a non-toxic drug and also has no adverse effects on each dose group in the chronic toxicity test compared with the control. It is indicated that Banqi oral liquid is safe and non-toxic and can be used in clinical trials.
To investigate the acute and chronic toxicity as well as to evaluate the safety level of Banqi( oral liquid). For acute pre toxicity test,performed at the maximum dose( 270 g/kg) of Banqi were drench to the mice.For chronic toxicity,based and compared to the dose of Banqi( oral liquid) used in pigs,we randomly and equally divided 80 rats into 4 groups into 4 groups( half male and half female),the low-dose( 20 times of pig dose i.e.10 g/kg),medium-dose( 40 times i. e. 20 g/kg),high-dose( 80 times dose i. e. 40 g/kg) and the control group( equal volume of water). 1 m L·100 g~(-1) body weight of Banqi was drenched once a day for 30 days.The clinical signs and behavioral activities of the rats were observed during this period. At 24 h and at 15 d of Banqi oral liquid cessation,body weight,hematology,blood biochemistry and histopathology were performed. The Acute toxicity test showed that Banqi( oral liquid) is a non-toxic drug and also has no adverse effects on each dose group in the chronic toxicity test compared with the control. It is indicated that Banqi oral liquid is safe and non-toxic and can be used in clinical trials.
引文
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[12]马丽,史业东,陈苏宁.益心康对体外心肌细胞感染柯萨奇病毒B_3影响的实验研究[J].实用药物与临床,2011,14(4):279-280.Ma L,Shi Y D,Chen S N,Effect of Yixinkang soup on cardiocytes of suckling rats infected by CVB 3 virus[J]. Practical Pharmacy And Clinical Remedies,2011,14(4):279-280.
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[2]侯宪邦.板蓝根潜在药效成分的发现及其作用机制的研究[D].南京中医药大学,2017.Hou X B,Research of the Potential Pharmacodynamic Ingreduents of Radix Isatidis and Mechanosm[D]. Nanjing University of Chinese Medicine,2017.
[3]李博,朱平先,许顶立.丹参酮ⅡA对自身免疫性心肌炎作用机制的研究进展[J].实用临床医学,2017,18(6):97-99.Li B,Zhu P X,Xu D L. Research Progress in Action Mechanisms of TanshinoneⅡA on Autoimmune Myocarditis[J].Practical Clinical Medicine,2017,18(6):97-99.
[4]杜晋平,薛翼鹏,张文杰,等.黄芪多糖对动物作用机制的研究[J].黑龙江畜牧兽医,2013(15):000030-32.Du J P,Xue Y P,Zhang W J,et al. Study on the Mechanism of Action of Astragalus Polysaccharides on Animals[J]. Heilongjiang Animal Science and Veterinary Medicine,2013(15):000030-32.
[5]刘爽,刘晓玲,张勇,等.黄芪多糖对CVB3感染的心肌细胞和心肌的保护作用研究[J].中国分子心脏病学杂志,2015(4):1407-1411.Liu S,Liu X L,Zhang Y,et al. Studied Protective Effect of Astragalus Polysaccharide on Myocardial Cell and Myocardium that were Infected by CVB3[J]. Chinese Journal of Molecular Cardiology,2015(4):1407-1411.
[6]刘灏,呼日乐巴特,熊英,等.黄芪总黄酮对病毒性心肌炎小鼠心律失常与内质网应激因子的影响[J].中国应用生理学杂志,2018,34(1).Liu H,Hurile B T,Xiong Y,et al. Effects of total flavonids of astragalus on arrhythmia,endoplasmic reticulum stress in mice with viral myocarditis[J]. Chinese Journal of Applied Physiology,2018,34(1).
[7]丁婵,褚秀玲,苏建青,等.黄芩苷抗病毒作用研究进展[J].中兽医医药杂志,2016(2):27-29.Ding C,Chu X L,Su J Q,et al. Advances in antiviral effects of baicalin[J]. Journal of Traditional Chinese Veterinary Medicine,2016(2):27-29.
[8]农业部兽药评审中心.兽药研究技术指导原则汇编[M].化学工业出版社,2012.Veterinary Drug Assessment of Ministry of Agriculture. Veterinary Drug Test Regulation Assemble[M]. Chemical Industry Press,2012.
[9]姜玲玲,陈鸿宇,史开志,等.一种新兽用止泻中药复方制剂对大鼠的急性及亚慢性毒性试验[J].中国畜牧兽医,2016,43(11):3073-3079.Jiang L L. Chen H Y,Shi K Z,et al. Acute and Sub-chronic Toxicity Test on Rats of a New Kind of Antidiarrheal Chinese Herbal Medicine Compound Preparation for Livestock[J]. China Animal Husbandry&Veterinary Medicine,2016,43(11):3073-3079.
[10]刘明怀.黄芪注射液对病毒性心肌炎TNF-α、IL-1和IL-6的影响[J].实用中医药杂志,2006,22(6):329-330.Liu M H,Effect on TNF-α,IL-1 and IL-6 of Viral Myocarditis Treated by Radix Astragali Injection[J]. Journal of Practical Traditional Chinese Medicine,2006,22(6):329-330.
[11]桂俊.黄芪治疗病毒性心肌炎的分子机制[D].复旦大学,2013.Gui J,The Molecular Mechanism for Astragalus in the Treatment of Viral Myocarditis[D]. Fudan University,2013.
[12]马丽,史业东,陈苏宁.益心康对体外心肌细胞感染柯萨奇病毒B_3影响的实验研究[J].实用药物与临床,2011,14(4):279-280.Ma L,Shi Y D,Chen S N,Effect of Yixinkang soup on cardiocytes of suckling rats infected by CVB 3 virus[J]. Practical Pharmacy And Clinical Remedies,2011,14(4):279-280.
[13]何伟.益气活血中药复方治疗CVB_3病毒性心肌炎的实验研究[D].辽宁中医药大学,2009.He W,Experimental study on the treatment of CVB_3 viral myocarditis with Yiqihuoxue Chinese herbal compound[D]. Liaoning University of Chinese Medicine,2009.