一个高通量肝代谢相互作用芯片,用于深入了解三托利德的毒性机制
Siyu Liu1, Yun Yang1, Yifei Yang1
1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Beijing, 100700, China. syliu2024@163.com.
Lab on a chip
|January 28, 2026
概括
一个新的高通量肝器官芯片 (HLKOC) 系统通过结合肝脏代谢来增强药物毒性测试. 这种先进的模型揭示了triptolide.
科学领域:
- 生物医学工程 生物医学工程
- 毒理学 毒理学 毒理学
- 芯片上的器官技术
背景情况:
- 目前的器官芯片 (OoC) 模型缺乏肝脏代谢,限制了它们在评估药物诱导毒性方面的准确性.
- 高通量查对于有效的药物开发和毒性评估至关重要.
研究的目的:
- 开发和验证一个高通量肝器官在芯片上的系统 (HLKOC).
- 使用HLKOC系统调查三类 (TPL) 的毒性及其机制.
- 为了证明HLKOC对单脏OOC模型的优势,用于药物毒性评估.
主要方法:
- 开发一个微流体HLKOC系统,集成精密切割肝脏切片 (PCLS) 和3D细胞球形.
- 优化内皮屏障功能,肝脏和脏组织活力,以及代谢活动.
- 整合多奥米克分析 (代谢学,转录学),生化分析和计算毒理学来研究TPL毒性.
主要成果:
- 该HLKOC系统展示了强大的肝脏生物合成能力,并比单个脏OoC更有效地模拟了体内条件.
- 在HLKOC系统中,仅检测到三化物诱导的尿素升高,这表明了毒性,这突显了其优越的灵敏度.
- 多omics分析显示TPL诱导的酸代谢变化,囊泡介导的过程,以及关键运输蛋白的下调 (cubilin,GLUT1).
结论:
- 高通量肝器官芯片 (HLKOC) 系统为药物诱导毒性评估提供了更高的灵敏度和准确性.
- 与单个器官模型相比,HLKOC系统为药物毒性提供了更深入的机械洞察力.
- 这种先进的模型具有改善临床前药物安全性评估的巨大潜力.
相关概念视频
What is Metabolism?
131.7K
Overview
131.7K
Kidney Structure
75.1K
The kidneys are two large bean-shaped organs located in the upper abdomen. They filter the blood several times a day to remove toxins and rebalance water and electrolytes of the circulatory system via the renal veins. The kidneys receive blood directly from the heart via the renal arteries. These arteries enter the kidney at the hilum, the concave surface of the bean, where they branch and divide into smaller vessels and capillaries.
75.1K
Reaction Mechanisms
30.7K
Chemical reactions often occur in a stepwise fashion, involving two or more distinct reactions taking place in a sequence. A balanced equation indicates the reacting species and the product species, but it reveals no details about how the reaction occurs at the molecular level. The reaction mechanism (or reaction path) provides details regarding the precise, step-by-step process by which a reaction occurs.
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
30.7K
Carbohydrate Metabolism
14.2K
Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
14.2K
Chromatin Immunoprecipitation- ChIP
12.3K
Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
12.3K
Liver Histology
4.3K
The microscopic anatomy of the liver is a complex and intricate system that comprises numerous structural units known as liver lobules, each of which is comparable in size to a sesame seed. These hexagonal structures consist of plates of liver cells or hepatocytes, which are characterized by their versatility and abundance of cellular apparatus like rough and smooth ER, Golgi apparatus, peroxisomes, and mitochondria.
Hepatocytes perform a variety of essential functions. They secrete...
Hepatocytes perform a variety of essential functions. They secrete...
4.3K


