首页|基于生化指标与代谢组学特征关联探索热毒宁注射液与青霉素注射液序贯用药的风险"时间窗"

基于生化指标与代谢组学特征关联探索热毒宁注射液与青霉素注射液序贯用药的风险"时间窗"

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采用检测血清生化指标与血浆代谢组学特征关联探索热毒宁注射液(Reduning，RDN)与青霉素注射液(penicillin G，PG)序贯用药风险"时间窗"，以期降低二者联用引发不良反应发生风险。所有动物实验操作和福利均遵循河南中医药大学第一附属实验动物伦理与动物福利委员会要求(批号:YFYDW2020002)。利用ELISA检测大鼠血清中生化指标的含量变化检测相关过敏指标，判定出RDN联用PG能引起由补体途径激活后的类过敏反应(pseudo-allergic reactions，PARs)。进一步对二者设置不同时间给药间隔(1。5、2、3。5、4、6和 8 h PG+RDN)进行考察，发现在3。5 h以内序贯给药，均能引起明显的PARs;而给药间隔超过4 h后PARs则明显减轻。同时采用LC-MS进行血浆代谢组学分析，平行比较大鼠的血清生化指标水平与血浆代谢轮廓特征，筛选出22个差异代谢物在3。5 h前后呈现出与生化指标相似或相反的变化趋势。并富集到花生四烯酸代谢、甾体激素生物合成代谢、亚油酸代谢、甘油磷脂代谢、色氨酸代谢等10条类过敏相关通路。综上所述，RDN和PG序贯使用所导致的药物不良反应确实存在风险"时间窗"现象，在"时间窗"之后的间隔用药能有效降低不良反应发生风险。
Exploring the risk"time interval window"of sequential medication of Reduning injection and penicillin G injection based on the correlation between biochemical indexes and metabolomics characteristics
Exploring the risk"time interval window"of sequential medication of Reduning injection(RDN)and penicillin G injection(PG)by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics,in order to reduce the risk of adverse reactions caused by the combination of RDN and PG.All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine(approval number:YFYDW2020002).The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay.It was determined that RDN combined with PG could cause pseudo-allergic reactions(PARs)activated by complement pathway.Further investigation was carried out at different time intervals(1.5,2,3.5,4,6,and 8 h PG+RDN).It was found that sequential administration within 3.5 h could cause significant PARs.However,PARs were significantly reduced after administration interval of more than 4 h.LC-MS was used for plasma metabolomics analysis,and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel.22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h.And enriched to 10 PARs-related pathways such as arachidonic acid metabolism,steroid hormone biosynthesis,linoleic acid metabolism,glycerophospholipid metabolism,and tryptophan metabolism.In conclusion,there is a risk"time interval window"phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG,and the interval medication after the"time interval window"can significantly reduce the risk of adverse reactions.

combination of Chinese and Western medicineadverse drug reactiontime interval windowReduning injectionpenicillin G injectionpseudo-allergic reactionmetabonomicsarachidonic acid metabolism

张明亮、陈毓龙、王晓艳、陈小菲、张辉、吴娅丽、杨柳青、张书琦、牛璐、冯科冉、李伟霞、唐进法

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河南中医药大学第一附属医院药学部,河南省中药临床应用、评价与转化工程研究中心,河南省中药临床药学中医药重点实验室,河南省中药安全评价与风险防控工程研究中心,河南郑州 450003

河南中医药大学,河南郑州 450046

河南中医药大学呼吸疾病中药防治省部共建协同创新中心,河南郑州 450046

中西药联用 药物不良反应 时间窗 热毒宁注射液 青霉素注射液 类过敏反应 代谢组学 花生四烯酸代谢

河南省科技攻关课题河南省高校科技创新团队河南省中医药拔尖人才培养项目

20210231018523IRTSTHN026豫中医科教[2018]35号

2024

10.16438/j.0513-4870.2023-1311

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子：1.274
ISSN：0513-4870
年,卷(期)：2024.59(7)
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