醋甘遂活性部位各成分群对斑马鱼胚胎的急性毒性比较研究(1)
[摘要]采用模式生物斑马鱼的胚胎评价醋甘遂活性部位各成分群急性毒性，同时采用UFLCQTOFMS对各成分群的化学成分进行定性研究。以24 h健康斑马鱼胚胎为研究对象，各成分群设9个浓度和1个空白对照组，考察给药后96 h其对斑马鱼胚胎存活率的影响，计算不同样品对斑马鱼胚胎的半数致死浓度(LC50)。结果显示，各成分群对斑马鱼胚胎的急性毒性大小依次为B>C>A>D，成分群D的毒性不明显。UFLCQTOFMS分析结果显示成分群B主要检测到巨大戟烷型二萜类成分，成分群C主要检测到假白榄烷型二萜类成分。关联毒性研究结果，推测假白榄烷型二萜类成分可能为醋甘遂中更为低毒的活性成分，可为进一步深入探究醋甘遂“有故无殒”的物质基础提供依据。
[关键词]醋甘遂； 成分群； UFLCQTOFMS； 斑马鱼胚胎； 急性毒性
Comparative study on acute toxicity of different active ingredient
, 百拇医药
fractions from Kansui stirbaked with vinegar on zebrafish embryos
LOU Jianwei， CAO Liangliang， ZHANG Qiao， ZHANG Li*， DING Anwei
(Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization， National and
Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine，Nanjing University of Chinese Medicine， Nanjing 210023， China)
, 百拇医药
[Abstract]The 24 h normal developing zebrafish embryos were used to evaluate the acute toxicity and the compounds of respective fractions were analyzed by UFLCQTOFMS simultaneously Nine concentration groups with respective concentration and a blank control group were designed for each fraction to investigate their effect on survival rates of zebrafish embryos 96 h after drug administration， and calculate the median lethal concentration (LC50) of different fractions to zebrafish embryos The results showed that all of the fractions had acute toxicity to zebrafish embryos except VEKD， and the order was as follows： VEKB， VEKC， VEKA and VEKD According to the results of UFLCQTOFMS， the chemical ingredients contained in VEKB and VEKC were mainly composed of ingenanetype and japhanetype diterpenoids， respectively It could be speculated that japhanetype diterpenoids might be the active compounds with lower toxicity associated with the results of toxicity study， providing some references for the further research on effective material basis of Kansui stirbaked with vinegar according to the principle of "drastic medicine， no death risks"
, http://www.100md.com
[Key words]Kansui stirbaked with vinegar； ingredients； UFLCQTOFMS； zebrafish embryos； acute toxicity
中药甘遂为大戟科植物甘遂Euphorbia kansui TN Liou ex TP Wang的干燥块根[1]。性味寒苦，有毒，常用于治疗胸腹积水、二便不利等症，临床内服需醋炙，以降低毒性及缓和药性。本课题组前期从腹水量、尿量、对肾素血管紧张素Ⅱ醛固酮系统的影响等多方位考察了醋甘遂各极性部位对Walker256癌性腹水模型大鼠的泻水逐饮功效，表明醋甘遂乙酸乙酯部位为其泻水逐饮活性部位[2]，但其功效成分仍待深入研究。醋甘遂较生品毒性降低，在癌性腹水模型大鼠上表现为“有故无殒”，但在正常动物上醋甘遂仍表现出一定的肝、胃、肠毒性，其毒性研究不可忽视[3]。模式动物斑马鱼较小鼠等哺乳类实验动物具有低成本、易于观察且重复性好等优点，相对于细胞又更能体现中医整体理论，近年来已被广泛应用于中药毒性研究[4]。故本實验拟分离醋甘遂泻水逐饮活性部位各成分群，采用模式生物斑马鱼的胚胎对各成分群进行急性毒性评价，同时结合UFLCQTOFMS对各成分群的化学成分进行定性分析，以期为揭示醋甘遂活性成分群泻水逐饮的物质基础提供一定的依据。, 百拇医药(楼坚伟 曹亮亮 张桥 张丽)
[关键词]醋甘遂； 成分群； UFLCQTOFMS； 斑马鱼胚胎； 急性毒性
Comparative study on acute toxicity of different active ingredient
, 百拇医药
fractions from Kansui stirbaked with vinegar on zebrafish embryos
LOU Jianwei， CAO Liangliang， ZHANG Qiao， ZHANG Li*， DING Anwei
(Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization， National and
Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine，Nanjing University of Chinese Medicine， Nanjing 210023， China)
, 百拇医药
[Abstract]The 24 h normal developing zebrafish embryos were used to evaluate the acute toxicity and the compounds of respective fractions were analyzed by UFLCQTOFMS simultaneously Nine concentration groups with respective concentration and a blank control group were designed for each fraction to investigate their effect on survival rates of zebrafish embryos 96 h after drug administration， and calculate the median lethal concentration (LC50) of different fractions to zebrafish embryos The results showed that all of the fractions had acute toxicity to zebrafish embryos except VEKD， and the order was as follows： VEKB， VEKC， VEKA and VEKD According to the results of UFLCQTOFMS， the chemical ingredients contained in VEKB and VEKC were mainly composed of ingenanetype and japhanetype diterpenoids， respectively It could be speculated that japhanetype diterpenoids might be the active compounds with lower toxicity associated with the results of toxicity study， providing some references for the further research on effective material basis of Kansui stirbaked with vinegar according to the principle of "drastic medicine， no death risks"
, http://www.100md.com
[Key words]Kansui stirbaked with vinegar； ingredients； UFLCQTOFMS； zebrafish embryos； acute toxicity
中药甘遂为大戟科植物甘遂Euphorbia kansui TN Liou ex TP Wang的干燥块根[1]。性味寒苦，有毒，常用于治疗胸腹积水、二便不利等症，临床内服需醋炙，以降低毒性及缓和药性。本课题组前期从腹水量、尿量、对肾素血管紧张素Ⅱ醛固酮系统的影响等多方位考察了醋甘遂各极性部位对Walker256癌性腹水模型大鼠的泻水逐饮功效，表明醋甘遂乙酸乙酯部位为其泻水逐饮活性部位[2]，但其功效成分仍待深入研究。醋甘遂较生品毒性降低，在癌性腹水模型大鼠上表现为“有故无殒”，但在正常动物上醋甘遂仍表现出一定的肝、胃、肠毒性，其毒性研究不可忽视[3]。模式动物斑马鱼较小鼠等哺乳类实验动物具有低成本、易于观察且重复性好等优点，相对于细胞又更能体现中医整体理论，近年来已被广泛应用于中药毒性研究[4]。故本實验拟分离醋甘遂泻水逐饮活性部位各成分群，采用模式生物斑马鱼的胚胎对各成分群进行急性毒性评价，同时结合UFLCQTOFMS对各成分群的化学成分进行定性分析，以期为揭示醋甘遂活性成分群泻水逐饮的物质基础提供一定的依据。, 百拇医药(楼坚伟 曹亮亮 张桥 张丽)