复方苦玄参颗粒急性毒性和亚慢性毒性试验
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摘要
【目的】分析复方苦玄参颗粒对昆明小鼠的急性毒性作用和对Wistar大鼠的亚慢性毒性作用,评价其用药安全性,为复方苦玄参颗粒的兽医临床用药提供理论依据。【方法】急性毒性试验以SPF级昆明小鼠为研究对象,分3次灌胃,测定复方苦玄参颗粒对昆明小鼠的急性毒性作用。亚慢性毒性试验选取Wistar大鼠为研究对象,设高、中、低3个剂量组[13.40、6.70和3.35 g/kg(以复方颗粒计)],每天灌胃给药1次,连续给药35 d,分别于第1、7、14、21、28和35 d称重,给药结束后对各剂量组Wistar大鼠(雌、雄各半)进行眼球采血,用于血常规指标和血清生化指标检测;同时采集肝脏、脾脏、肺脏、肾脏、胃、肠道、睾丸(♂)或子宫(♀)等器官称重,计算各器官的脏器系数,以及固定后制作石蜡切片,用于组织病理学检测。【结果】急性毒性试验结果表明,昆明小鼠在最大给药量(80.40 g/kg)下未表现出任何毒性反应,解剖也未发现明显可见的病理变化。亚慢性毒性试验结果显示,各剂量组Wistar大鼠的体重、血常规指标、血清生化指标和脏器系数与对照组(生理盐水灌胃)Wistar大鼠相比均未发生显著变化(P>0.05);经剖检和组织病理学检查,发现高剂量组和对照组Wistar大鼠的脾脏、肺脏、肝脏、肾脏、胃、肠道、睾丸(♂)或子宫(♀)等器官组织均未出现异常病理变化。【结论】复方苦玄参颗粒无急性毒性作用,长期用药也不会产生亚慢性毒性作用,具有很高的用药安全性,可在兽医临床上推广应用。
【Objective】This study was aimed to analyze the acute toxicity of Compound Kuxuanshen Granules to Kunming mice and subchronic toxicity to Wistar rats,evaluate its safety and provide the theoretical basis for the veterinary clinical administration route of Compound Kuxuanshen Granules.【Method】Acute toxicity test was conducted on SPF grade Kunming mice,which were administered for three times to determine the acute toxicity effect of Compound Kuxuanshen Granules. In the subchronic toxicity test,Wistar rats were selected as the study subjects. The high,middle and low dose groups[13.40,6.70 and 3.35 g/kg(in terms of compound granules)]were treated with intragastric administration once a day for continuous administration. During 35 d of continuous administration,each group was weighed on the 1 st,7 th,14 th,21 st,28 thand 35 thd respectively. After cessation of administration,Wistar rats(half were female and the other half were male)in each group were sampled on eyeball for blood routine indicators and serum biochemistry. At the same time,organs such as liver,spleen,lung,kidney,stomach,intestine,testis(♂)or uterus(♀)were collected and weighed,the organ coefficient of each organ was calculate. Then the organs were fixed and made into paraffin sections for histopathological examination.【Result】The results of the acute toxicity test showed that Kunming mice did not show any toxic reaction at the maximum dose(80.40 g/kg),and no obvious pathological changes were observed in the anatomy. Subchronic toxicity test results showed that the weight,blood routine index,serum biochemical index and organ coefficient of Wistar rats in each dose group did not change significantly compared with the control group(intragastric administration of saline)(P>0.05). After necropsy and histopathological examination,no abnormal pathology was found in the spleen,lung,liver,kidney,stomach,intestine,testis(♂)or uterus(♀)of Wistar rats between the high dose group and the control group.【Conclusion】The Compound Kuxuanshen Granules has no acute toxic effects,and long-term medication will not produce subchronic toxic effects. It has high drug safety and can be widely applied in veterinary clinics.
【Objective】This study was aimed to analyze the acute toxicity of Compound Kuxuanshen Granules to Kunming mice and subchronic toxicity to Wistar rats,evaluate its safety and provide the theoretical basis for the veterinary clinical administration route of Compound Kuxuanshen Granules.【Method】Acute toxicity test was conducted on SPF grade Kunming mice,which were administered for three times to determine the acute toxicity effect of Compound Kuxuanshen Granules. In the subchronic toxicity test,Wistar rats were selected as the study subjects. The high,middle and low dose groups[13.40,6.70 and 3.35 g/kg(in terms of compound granules)]were treated with intragastric administration once a day for continuous administration. During 35 d of continuous administration,each group was weighed on the 1 st,7 th,14 th,21 st,28 thand 35 thd respectively. After cessation of administration,Wistar rats(half were female and the other half were male)in each group were sampled on eyeball for blood routine indicators and serum biochemistry. At the same time,organs such as liver,spleen,lung,kidney,stomach,intestine,testis(♂)or uterus(♀)were collected and weighed,the organ coefficient of each organ was calculate. Then the organs were fixed and made into paraffin sections for histopathological examination.【Result】The results of the acute toxicity test showed that Kunming mice did not show any toxic reaction at the maximum dose(80.40 g/kg),and no obvious pathological changes were observed in the anatomy. Subchronic toxicity test results showed that the weight,blood routine index,serum biochemical index and organ coefficient of Wistar rats in each dose group did not change significantly compared with the control group(intragastric administration of saline)(P>0.05). After necropsy and histopathological examination,no abnormal pathology was found in the spleen,lung,liver,kidney,stomach,intestine,testis(♂)or uterus(♀)of Wistar rats between the high dose group and the control group.【Conclusion】The Compound Kuxuanshen Granules has no acute toxic effects,and long-term medication will not produce subchronic toxic effects. It has high drug safety and can be widely applied in veterinary clinics.
引文
陈君,甄汉深,韦建华.2013.苦玄参叶抗炎药理作用研究[J].海峡药学,25(2):23-25.[Chen J,Zhen H S,Wei JH.2013.Study on anti-inflammation of Picria feltarrae leaves[J].Strait Pharmaceutical Journal,25(2):23-25.]
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何龙,姚尧.2013.中药颗粒剂的研究现状及应用前景分析[J].中国当代医药,17(9):82-83.[He L,Yao Y.2013.Research status and application prospect of traditional Chinese medicine granules[J].China Modern Medicine,17(9):82-83.]
洪伟鸣,左伟勇,宋亮,黄文强,郁杰.2013.鸡支康口服液的亚慢性毒性试验研究[J].中国畜牧兽医,40(9):140-143.[Hong W M,Zuo W Y,Song L,Huang W Q,Yu J.2013.Study on subchronic toxicity test of Jizhikang oral liquid[J].China Animal Husbandry&Veterinary Medicine,40(9):140-143.]
黄燕,肖艳芬,甄汉深,陈君.2008.苦玄参体外抗菌作用的实验研究[J].广西中医药,31(1):46-47.[Huang Y,Xiao Y F,Zhen H S,Chen J.2008.Experimental study of in vitro antibacterial activity of bitter Scrophulariaceae[J].Guangxi Journal of Traditional Chinese Medicine,31(1):46-47.]
靳二辉,周先建,孙启,周金星,李升和,金光明.2018.复方中草药制剂对肉鸡肌肉发育和肉品质的影响[J].江苏农业学报,34(2):374-384.[Jin E H,Zhou X J,Sun Q,Zhou J X,Li S H,Jin G M.2018.The effect of compound Chinese herbal preparation on muscle development and meat quality of broiler[J].Jiangsu Journal of Agricultural Sciences,34(2):374-384.]
李海燕.2015.三参滋胃颗粒的稳定性及作用机制研究[D].长春:吉林大学.[Li H Y.2015.The feasibility and the mechanism of Sanshenziweikeli in treating chronic atrophic gastritis[D].Changchun:Jinlin University.]
李萍,周芳,陈勇.2007.苦玄参提取物解热作用的实验研究[J].时珍国医国药,18(11):2638.[Li P,Zhou F,Chen Y.2007.Study on the antipyretic effects of Picria felterrae Lour.[J].Lishizhen Medicine and Materia Medica Research,18(11):2638.]
李艳华,闫清波,于康震,佟恒敏,孙元.2008.复方中药对禽流感病毒的防治研究[J].中国农业科学,41(5):1511-1518.[Li Y H,Yan Q B,Yu K Z,Tong H M,Sun Y.2008.Study of the compound Chinese medicine against the anti-avian influenza virus[J].Scientia Agricultura Sinica,41(5):1511-1518.]
李玉平.2012.清肺平喘颗粒的临床前研究[D].重庆:西南大学.[Li Y P.2012.Preclinical study on Qingfei Pingchuan granules[D].Chongqing:Southwest University.]
秦秀霞.2014.苦玄参药理研究进展[J].亚太传统医药,10(2):41-42.[Qin X X.2014.Research progress on pharmacology of Picria felterrae Lour.[J].Asia-Pacific Traditional Medicine,10(2):41-42.]
邱灿华,陈健文,李晓君,蓝秀健,余剑平,林明栋.2008.苦参提取物对大鼠胸主动脉环张力的影响及其机制探讨[J].深圳中西医结合杂志,18(1):4-6.[Qiu C H,Chen J W,Li X J,Lan X J,Yu J P,Lin M D.2008.Effects of sophora extract on the tension of thoracic aorta in rats and its mechanism[J].Shenzhen Journal of Integrated Traditional Chinese and Western Medicine,18(1):4-6.]
王奇志,陈雨,王鸣,冯煦.2010.苦草提取物Pft-d对小鼠S180肉瘤、肝癌Heps的抗癌作用及体外细胞毒活性实验研究[J].现代药物与临床,25(2):134-137.[Wang Q Z,Chen Y,Wang M,Feng X.2010.Study on antitumor activities of extracts Pft-d from Picria felterrae[J].Drugs&Clinic,25(2):134-137.]
王志敬,何翔,陈彩文,高振华,石琳.2016.中草药添加剂对AA肉鸡肌肉品质和风味物质含量的影响[J].河南农业科学,45(10):146-150.[Wang Z J,He X,Chen C W,Gao Z H,Shi L.2016.Effects of Chinese herbs on muscle quality and flavor compounds in AA broilers[J].Journal of Henan Agricultural Sciences,45(10):146-150.]
吴建璋,文永新,黄永林,李典鹏,陈月圆.2012.苦玄参提取物对小鼠的抗炎及镇痛作用[J].中国医院药学杂志,32(16):1303-1304.[Wu J Z,Wen Y X,Huang Y L,Li DP,Chen Y Y.2012.The anti-inflammatory and analgesic effect of the extract of sophora japonicus in mice[J].Chinese Journal of Hospital Pharmacy,32(16):1303-1304.]
肖婷,崔炯谟,李倩,赵余庆.2013.桃金娘的化学成分、药理作用和临床应用研究进展[J].现代药物与临床,28(5):800-805.[Xiao T,Cui J M,Li Q,Zhao Y Q.2013.Research progress on chemical constituents,pharmacology and clinical application of Rhodomyrtus tomentosa[J].Drugs&Clinic,28(5):800-805.]
徐杨峰,聂海英,唐廷崇,彭健波,陶卿,何家康.2018.复方苦玄参颗粒质量标准初步研究[J].动物医学进展,39(8):59-63.[Xu Y F,Nie H Y,Tang T C,Peng J B,Tao Q,He J K.2018.Study on quality standard of Compound Kuxuanshen Granul[J].Progress in Veterinary Medicine,39(8):59-63.]
于开彬.2008.浅析中药配方颗粒的优势与不足[J].内蒙古中医药,(7):31.[Yu K B.2008.A brief analysis of the advantages and disadvantages of Chinese medicine formula granules[J].Nei Mongol Journal of Traditional Chinese Medicine,(7):31]
周芳,李萍,陈勇,陆孟引.2006.苦玄参干浸膏抗炎镇痛作用的实验研究[J].中国中医药科技,13(4):244-245.[Zhou F,Li P,Chen Y,Lu M Y.2006.Experimental study on anti-inflammatory and analgesic of Picria felterrae Lour.[J].Chinese Journal of Traditional Medical Science and Technology,13(4):244-245.]
Limsuwan S,Voravuthikunchai S P.2008.Boesenbergia pandurata(Roxb.)Schltr.,Eleutherine americana Merr.and Rhodomyrtus tomentosa(Aiton)Hassk.as antibiofilm producing and antiquorum sensing in Streptococcus pyogenes[J].FEMS Immunology and Medical Microbiology,53(3):429-436.
Sepici-Dincel A,A?ikg?z S,Cevik C,Sengelen M,Ye?ilada E.2007.Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits[J].Journal of Ethnopharmacology,110(3):498-503.
陈旭,杜正彩.2010.桃金娘多糖对大鼠急性肝损伤保护作用的研究[J].安徽农业科学,38(11):5644.[Chen X,Du Z C.2010.Protective effect of myrtle polysaccharide on acute liver injury in rats[J].Journal of Anhui Agricultural Sciences,38(11):5644.]
何龙,姚尧.2013.中药颗粒剂的研究现状及应用前景分析[J].中国当代医药,17(9):82-83.[He L,Yao Y.2013.Research status and application prospect of traditional Chinese medicine granules[J].China Modern Medicine,17(9):82-83.]
洪伟鸣,左伟勇,宋亮,黄文强,郁杰.2013.鸡支康口服液的亚慢性毒性试验研究[J].中国畜牧兽医,40(9):140-143.[Hong W M,Zuo W Y,Song L,Huang W Q,Yu J.2013.Study on subchronic toxicity test of Jizhikang oral liquid[J].China Animal Husbandry&Veterinary Medicine,40(9):140-143.]
黄燕,肖艳芬,甄汉深,陈君.2008.苦玄参体外抗菌作用的实验研究[J].广西中医药,31(1):46-47.[Huang Y,Xiao Y F,Zhen H S,Chen J.2008.Experimental study of in vitro antibacterial activity of bitter Scrophulariaceae[J].Guangxi Journal of Traditional Chinese Medicine,31(1):46-47.]
靳二辉,周先建,孙启,周金星,李升和,金光明.2018.复方中草药制剂对肉鸡肌肉发育和肉品质的影响[J].江苏农业学报,34(2):374-384.[Jin E H,Zhou X J,Sun Q,Zhou J X,Li S H,Jin G M.2018.The effect of compound Chinese herbal preparation on muscle development and meat quality of broiler[J].Jiangsu Journal of Agricultural Sciences,34(2):374-384.]
李海燕.2015.三参滋胃颗粒的稳定性及作用机制研究[D].长春:吉林大学.[Li H Y.2015.The feasibility and the mechanism of Sanshenziweikeli in treating chronic atrophic gastritis[D].Changchun:Jinlin University.]
李萍,周芳,陈勇.2007.苦玄参提取物解热作用的实验研究[J].时珍国医国药,18(11):2638.[Li P,Zhou F,Chen Y.2007.Study on the antipyretic effects of Picria felterrae Lour.[J].Lishizhen Medicine and Materia Medica Research,18(11):2638.]
李艳华,闫清波,于康震,佟恒敏,孙元.2008.复方中药对禽流感病毒的防治研究[J].中国农业科学,41(5):1511-1518.[Li Y H,Yan Q B,Yu K Z,Tong H M,Sun Y.2008.Study of the compound Chinese medicine against the anti-avian influenza virus[J].Scientia Agricultura Sinica,41(5):1511-1518.]
李玉平.2012.清肺平喘颗粒的临床前研究[D].重庆:西南大学.[Li Y P.2012.Preclinical study on Qingfei Pingchuan granules[D].Chongqing:Southwest University.]
秦秀霞.2014.苦玄参药理研究进展[J].亚太传统医药,10(2):41-42.[Qin X X.2014.Research progress on pharmacology of Picria felterrae Lour.[J].Asia-Pacific Traditional Medicine,10(2):41-42.]
邱灿华,陈健文,李晓君,蓝秀健,余剑平,林明栋.2008.苦参提取物对大鼠胸主动脉环张力的影响及其机制探讨[J].深圳中西医结合杂志,18(1):4-6.[Qiu C H,Chen J W,Li X J,Lan X J,Yu J P,Lin M D.2008.Effects of sophora extract on the tension of thoracic aorta in rats and its mechanism[J].Shenzhen Journal of Integrated Traditional Chinese and Western Medicine,18(1):4-6.]
王奇志,陈雨,王鸣,冯煦.2010.苦草提取物Pft-d对小鼠S180肉瘤、肝癌Heps的抗癌作用及体外细胞毒活性实验研究[J].现代药物与临床,25(2):134-137.[Wang Q Z,Chen Y,Wang M,Feng X.2010.Study on antitumor activities of extracts Pft-d from Picria felterrae[J].Drugs&Clinic,25(2):134-137.]
王志敬,何翔,陈彩文,高振华,石琳.2016.中草药添加剂对AA肉鸡肌肉品质和风味物质含量的影响[J].河南农业科学,45(10):146-150.[Wang Z J,He X,Chen C W,Gao Z H,Shi L.2016.Effects of Chinese herbs on muscle quality and flavor compounds in AA broilers[J].Journal of Henan Agricultural Sciences,45(10):146-150.]
吴建璋,文永新,黄永林,李典鹏,陈月圆.2012.苦玄参提取物对小鼠的抗炎及镇痛作用[J].中国医院药学杂志,32(16):1303-1304.[Wu J Z,Wen Y X,Huang Y L,Li DP,Chen Y Y.2012.The anti-inflammatory and analgesic effect of the extract of sophora japonicus in mice[J].Chinese Journal of Hospital Pharmacy,32(16):1303-1304.]
肖婷,崔炯谟,李倩,赵余庆.2013.桃金娘的化学成分、药理作用和临床应用研究进展[J].现代药物与临床,28(5):800-805.[Xiao T,Cui J M,Li Q,Zhao Y Q.2013.Research progress on chemical constituents,pharmacology and clinical application of Rhodomyrtus tomentosa[J].Drugs&Clinic,28(5):800-805.]
徐杨峰,聂海英,唐廷崇,彭健波,陶卿,何家康.2018.复方苦玄参颗粒质量标准初步研究[J].动物医学进展,39(8):59-63.[Xu Y F,Nie H Y,Tang T C,Peng J B,Tao Q,He J K.2018.Study on quality standard of Compound Kuxuanshen Granul[J].Progress in Veterinary Medicine,39(8):59-63.]
于开彬.2008.浅析中药配方颗粒的优势与不足[J].内蒙古中医药,(7):31.[Yu K B.2008.A brief analysis of the advantages and disadvantages of Chinese medicine formula granules[J].Nei Mongol Journal of Traditional Chinese Medicine,(7):31]
周芳,李萍,陈勇,陆孟引.2006.苦玄参干浸膏抗炎镇痛作用的实验研究[J].中国中医药科技,13(4):244-245.[Zhou F,Li P,Chen Y,Lu M Y.2006.Experimental study on anti-inflammatory and analgesic of Picria felterrae Lour.[J].Chinese Journal of Traditional Medical Science and Technology,13(4):244-245.]
Limsuwan S,Voravuthikunchai S P.2008.Boesenbergia pandurata(Roxb.)Schltr.,Eleutherine americana Merr.and Rhodomyrtus tomentosa(Aiton)Hassk.as antibiofilm producing and antiquorum sensing in Streptococcus pyogenes[J].FEMS Immunology and Medical Microbiology,53(3):429-436.
Sepici-Dincel A,A?ikg?z S,Cevik C,Sengelen M,Ye?ilada E.2007.Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits[J].Journal of Ethnopharmacology,110(3):498-503.