摘要
目的研究麻黄细辛附子汤(MXF)对正常小鼠的毒性作用机制。方法将48只SPF级BABL/C小鼠随机分为空白组和MXF低、中、高剂量组,每组12只。MXF低、中、高剂量组小鼠分别按照11.262、33.786、45.050 g/kg的剂量灌胃给药,空白组小鼠灌胃等体积生理盐水,每日1次,连续灌胃7 d,记录体质量、肛温、生存率,并检测脏器指数、血清生化因子等指标。末次给药后收集小鼠粪便样品,采用超高效液相-质谱联用(UHPLC-QE/MS)技术检测。结果与空白组相比,MXF中剂量组小鼠在给药第3~5天、MXF高剂量组小鼠给药第2~7天体质量显著低于空白组(P<0.05);各给药组小鼠肛温差异无统计学意义;MXF中、高剂量组小鼠的生存率分别为58.33%、50.00%。与空白组相比,MXF低、中、高剂量组小鼠的脾、肺、胸腺、肾上腺指数和肌酸激酶,MXF低、高剂量组小鼠的睾丸指数,MXF低剂量组小鼠的肌酸激酶同工酶与肌酸激酶比值,MXF中剂量组α-羟丁酸脱氢酶、乳酸脱氢酶、碱性磷酸酶,MXF中、高剂量组小鼠的尿素和胱抑素C的差异均有统计学意义(P<0.05)。经粪便代谢组学分析发现,MXF低、中、高剂量组中苯丙酮酸、L-酪氨酸、磷脂酰胆碱、3-磷酸甘油等19个生物标志物与空白组的差异均有统计学意义。结论MXF达到一定剂量会对小鼠体质量、多脏器和血清生化指标产生不良影响,从而表现出一定的毒性作用,其作用机制可能与扰乱机体的肠道菌群代谢、引起炎症反应和造成免疫失调有关。
OBJECTIVE To study the toxic mechanism of Mahuang xixin fuzi decoction(MXF)on normal mice.METHODS Totally 48 SPF grade BABL/C mice were randomly divided into blank group,MXF low-dose,medium-dose and high-dose groups,with 12 mice in each group.MXF low-dose,medium-dose and high-dose groups were given drug intragastrically at the dose of 11.262,33.786,45.050 g/kg,respectively.Blank group was administered with equal volume of normal saline,once a day,for consecutive 7 d.The body weight,anal temperature and survival rate were recorded,organ index and serum biochemical factors were detected.After the last administration,fecal samples of mice were collected and detected by UHPLC-QE/MS.RESULTS Compared with blank group,the body weight was decreased significantly from the 3rd to the 5th day after administration in MXF medium-dose group,and from the 2nd to the 7th day after administration in MXF high-dose group significantly(P<0.05).There was no significant difference in anal temperature among the treatment groups;the average survival rates of MXF medium-dose and high-dose groups were 58.33% and 50.00%,respectively.Compared with blank group,there were significant difference in the indexes of spleen,lung,thymus,adrenal gland and creatine kinase in MXF low-dose,medium-dose and high-dose groups,the testis index in MXF low-dose and high-dose groups,the creatine kinase isoenzyme/creatine kinase ratio in MXF low-dose group,the α-hydroxybutyrate dehydrogenase,lactate dehydrogenase and alkaline phosphatase in MXF medium-dose group,the urine and cystatin C in MXF medium-dose and high-dose groups(P<0.05).The fecal metabonomic analysis showed that 19 biomarkers such as phenylpyruvate,L-tyrosine,phosphatidylcholine,glycerol 3-phosphate in MXF low-dose,medium-dose and high-dose groups were significantly different from those in the blank group.CONCLUSIONS When MXF reaches a certain dose,it will have adverse effects on the body weight,multiple organs and serum biochemical indicators of mice,thus showing a certain toxic effect.Its mechanism may be related to disrupting the intestinal flora metabolism,causing inflammatory reaction and immune disorders.
作者
王耀东
李灿
杨勇
孙启慧
容蓉
WANG Yaodong;LI Can;YANG Yong;SUN Qihui;RONG Rong(School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Experimental Center,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)
出处
《中国药房》
CAS
北大核心
2023年第2期144-149,共6页
China Pharmacy
基金
国家自然科学基金资助项目(No.81873220)
山东省重点研发计划(重大科技创新工程)项目(No.2020CXGC010505)
济南市“新高校20条”资助项目(No.2021GXRC028)。
关键词
麻黄细辛附子汤
毒性作用
粪便代谢组学
Mahuang xixin fuzi decoction
toxic effects
fecal metabolomics
