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途径层次的多奥米克分析,对长期暴露于塔克罗利斯的毒性背后的分子机制进行分析

Nguyen Thi Hai Yen¹, Nguyen Ky Phat¹, Jung-Hwa Oh²

¹Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan 47392, Republic of Korea.

Toxicology and applied pharmacology

|June 15, 2023

概括

塔克罗利 (TAC) 通过分子干扰引起和肝脏损伤. 这项研究揭示了TAC毒性涉及氧化应激,代谢变化和细胞死亡途径,为其机制提供了洞察力.

科学领域:

毒理学毒理学毒理学
分子生物学分子生物学
药理学药理学是指药理学的学科.

背景情况:

塔克罗利 (TAC) 对于预防器官移植排斥至关重要,但与毒性和肝毒性有关.
导致TAC引起的器官损伤的精确分子机制尚不完全理解.

研究的目的:

为了阐明在肝脏和脏中Tacrolimus (TAC) 毒性背后的分子途径.
利用综合性奥米克方法,将转录组学和代谢组学结合起来进行全面的分析.

主要方法:

鼠每天服用口服塔克罗利马斯 (TAC) 剂量为5mg/kg,持续4周.
在肝脏和脏组织上进行了全基因组基因表达概况和非向代谢.
数据被单独分析,并使用途径级转录组学-代谢组学分析进行整合.

主要成果:

代谢障碍包括氧化剂-抗氧化剂状态,脂质和氨基酸代谢的失衡.
基因表达的变化表明免疫失调,炎症和编程细胞死亡.
综合分析将TAC毒性与DNA合成中断,氧化应激,细胞膜透,脂质/葡萄糖代谢改变联系起来.

结论:

综合性奥米克分析为TAC的分子毒理学提供了全面的理解.
研究结果强调氧化应激,代谢失调和细胞死亡是TAC诱导器官损伤的关键机制.
这项研究作为未来对TAC毒性机制研究的基础.

关键词:

代谢学代谢学代谢学多个omics的多个omics.多个器官的相互作用.毒性毒性毒性塔克罗利慕斯可以使用.文字转录学 (Transcriptomics) 是一个学科.

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