首页|马钱子致大鼠体内毒性的研究——"装袋"算法和16S rRNA基因测序技术在毒理学研究中的应用

马钱子致大鼠体内毒性的研究——"装袋"算法和16S rRNA基因测序技术在毒理学研究中的应用

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  • NSTL
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目的 中药马钱子(Strychnos nux-vomica L。，SN)在临床上具有消肿止痛的功效，然而，由于含有生物碱类成分，马钱子具有一定毒性。人们对马钱子毒性所引起的大鼠内源性代谢变化及其对肠道微生物群代谢失调的潜在影响知之甚少，因此，马钱子的毒理学研究对其安全性评价具有重要意义。本研究将代谢组学和16S rRNA基因测序技术相结合来探索马钱子的致毒机制。方法 通过急性、蓄积性和亚急性毒性试验，分别确定马钱子的中毒剂量、毒性强度和毒性靶器官。超高效液相色谱-质谱联用技术用于分析大鼠灌胃马钱子后的血清、肝脏和肾脏样本。利用基于装袋算法的决策树和K最近邻(K nearest neighbor，KNN)模型对组学数据进行分类。从大鼠粪便中提取样本后，使用高通量测序平台对细菌的16s rRNA V3-V4区域进行分析。结果 装袋算法提高了样本分类的准确率。共鉴定出12个生物标志物，这些生物标志物的代谢失调可能是马钱子致体内毒性的原因。拟杆菌、粪厌氧棒菌、颤螺菌、双茎体菌等与肾肝功能的生理指标密切相关，这表明马钱子引起的肝肾损害可能与这些肠道细菌的代谢紊乱有关。结论 本文揭示了马钱子的体内致毒机制，为马钱子临床上的安全合理使用提供了科学依据。
Study on The Toxicity of Strychnos nux-vomica L.in vivo in Rats:Application of Bagging Algorithm and 16S rRNA Gene Sequencing Technology in Toxicology Research
Objective The traditional Chinese medicine Strychnos nux-vomica L.(SN)has the clinical effect of reducing swelling and relieving pain;however,SN is toxic due to its alkaloid components.Little is known about the endogenous metabolic changes induced by SN toxicity in rats and their potential effects on the metabolic dysregulation of intestinal microbiota.Therefore,toxicological investigation of SN is of great significance to its safety assessment.In this study,the toxic mechanisms of SN were explored using a combination of metabonomics and 16S rRNA gene sequencing.Methods The toxic dose,intensity,and target organ of SN were determined in rats using acute,cumulative,and subacute toxicity tests.UHPLC-MS was used to analyze the serum,liver,and renal samples of rats after intragastric SN administration.The decision tree and K Nearest Neighbor(KNN)model were established based on the bootstrap aggregation(bagging)algorithm to classify the omics data.After samples were extracted from rat feces,the high-throughput sequencing platform was used to analyze the 16S rRNA V3-V4 region of bacteria.Results The bagging algorithm improved the accuracy of sample classification.Twelve biomarkers were identified,where their metabolic dysregulation may be responsible for SN toxicity in vivo.Several types of bacteria such as Bacteroidetes,Anaerostipes,Oscillospira and Bilophila,were demonstrated to be closely related to physiological indices of renal and liver function,indicating that SN-induced liver and kidney damage may be related to the disturbance of these intestinal bacteria.Conclusion The toxicity mechanism of SN was revealed in vivo,which provides a scientific basis for the safe and rational clinical use of SN.

Strychnosnux-vomica L.toxic mechanismmetabonomicsintestinal florabagging algorithm

王曦烨、宝乐尔、姜明洋、李丹、白梅荣

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内蒙古民族大学化学与材料学院,通辽 028000

内蒙古民族大学,天然产物化学及功能分子合成重点实验室,通辽 028000

内蒙古自治区药品检查中心,呼和浩特 010000

内蒙古民族大学计算机科学与技术学院,通辽 028000

内蒙古民族大学蒙医药研发工程教育部重点实验室,通辽 028000

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马钱子 致毒机制 代谢组学 肠道菌群 装袋算法

国家自然科学基金国家自然科学基金内蒙古自治区高等学校青年科技英才支持计划内蒙古自治区直属高校基本科研业务费内蒙古自治区高等学校创新团队发展计划内蒙古自然科学基金内蒙古自治区高等学校科学研究项目蒙医药研发工程教育部重点实验室开放基金内蒙古民族大学博士启动基金

8226084462162049NJYT23136GXKY22118NMGIRT22162021MS08072NJZY21430MDK2021041BS633

2024

10.16476/j.pibb.2023.0044

生物化学与生物物理进展
中国科学院生物物理研究所,中国生物物理学会

生物化学与生物物理进展

CSTPCD北大核心
影响因子：0.476
ISSN：1000-3282
年,卷(期)：2024.51(2)
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