Page 22 - 《中国药房》2023年2期
P. 22
基于粪便代谢组学的麻黄细辛附子汤毒性作用机制研究
Δ
1＊
1 #
王耀东 ，李 灿 ，杨 勇 ，孙启慧 ，容 蓉 （1.山东中医药大学药学院，济南 250355；2.山东中医药大学实
1
2
1
验中心，济南 250355）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2023）02-0144-06
DOI 10.6039/j.issn.1001-0408.2023.02.04
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。
关键词 麻黄细辛附子汤；毒性作用；粪便代谢组学
Study on the toxic mechanism of Mahuang xixin fuzi decoction based on fecal metabolomics
1
1
1
1
2
WANG Yaodong ，LI Can ，YANG Yong ，SUN Qihui ，RONG Rong （1. School of Pharmacy， Shandong
University of Traditional Chinese Medicine， Jinan 250355， China； 2. Experimental Center， Shandong University
of Traditional Chinese Medicine， Jinan 250355， China）
ABSTRACT 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
Δ 基金项目 国家自然科学基金资助项目（No.81873220）；山东省
biochemical indicators of mice， thus showing a certain toxic
重点研发计划（重大科技创新工程）项目（No.2020CXGC010505）；济南
effect. Its mechanism may be related to disrupting the intestinal
市“新高校20条”资助项目（No.2021GXRC028）
flora metabolism， causing inflammatory reaction and immune
＊第一作者 硕士研究生。研究方向：中药及复方活性成分与质量
控制。E-mail：1813948286@qq.com disorders.
# 通信作者 教授，博士生导师，博士。研究方向：中药及复方活性 KEYWORDS Mahuang xixin fuzi decoction； toxic effects；
成分与质量控制。E-mail：rosierong@163.com fecal metabolomics
· 144 · China Pharmacy 2023 Vol. 34 No. 2 中国药房 2023年第34卷第2期
