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基于拉索-logistic 回归模型筛选士的宁类生物碱致神经毒性的血清生物标志物。

Lasso-Logistic regression model for the identification of serum biomarkers of neurotoxicity induced by strychnos alkaloids.

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.

Department of Pharmacy, The First Hospital of China Medical University, Shenyang, China.

出版信息

Toxicol Mech Methods. 2023 Jan;33(1):65-72. doi: 10.1080/15376516.2022.2086088. Epub 2022 Aug 8.

Abstract

As a traditional Chinese medicine, strychnos alkaloids have wide effects including antitumor, analgesic, and anti-inflammatory. However, the therapeutic window of strychnos alkaloids is quite narrow due to potential neurotoxicity. Therefore, it is necessary to explore some efficient biomarkers to identify and predict the neurotoxicity induced by strychnos alkaloids and find a therapy to prevent the neurotoxicity of strychnos alkaloids. Based on the previous studies of our research team, 21 endogenous substances related to neurotoxicity were monitored in rats' serum with HPLC-MS/MS and ELISA. Starting from these fundamentals, a Lasso-Logistic regression model was used to select efficient biomarkers from 21 endogenous substances to predict brain injury and verify the neuroprotective effect of peonies. Under the processing of the Lasso-Logistic regression model, 12 biomarkers were identified from 21 endogenous substances to predict the neurotoxicity induced by strychnos alkaloids. At the same time, the neuroprotective effect of peonies was further confirmed by evaluating the level of 12 biomarkers. The results indicated that the development of the Lasso-Logistic regression model would provide a new, simple and efficient method for the prediction and diagnosis of the neurotoxicity induced by strychnos alkaloids.

摘要

作为一种传统中药,马钱子生物碱具有广泛的作用,包括抗肿瘤、镇痛和抗炎作用。然而,由于潜在的神经毒性,马钱子生物碱的治疗窗口相当狭窄。因此,有必要探索一些有效的生物标志物来识别和预测马钱子生物碱引起的神经毒性,并找到一种预防马钱子生物碱神经毒性的治疗方法。基于我们研究团队的先前研究,使用 HPLC-MS/MS 和 ELISA 监测了大鼠血清中与神经毒性相关的 21 种内源性物质。从这些基础出发,使用 Lasso-Logistic 回归模型从 21 种内源性物质中选择有效的生物标志物来预测脑损伤,并验证牡丹皮的神经保护作用。在 Lasso-Logistic 回归模型的处理下,从 21 种内源性物质中鉴定出 12 种生物标志物来预测马钱子生物碱引起的神经毒性。同时,通过评估 12 种生物标志物的水平,进一步证实了牡丹皮的神经保护作用。结果表明,Lasso-Logistic 回归模型的发展将为预测和诊断马钱子生物碱引起的神经毒性提供一种新的、简单和有效的方法。

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