摘要
本研究构建了一种高通量三维肝细胞模型,可模拟细胞在体内的三维生长空间,具有通量高、精密度好、成本低、操作简便的优势,可用于中药肝毒性的快速评价。首先,采用胶原水凝胶构建了三维高通量肝细胞芯片模型,以对乙酰氨基酚、昆明山海棠提取物和中药复方七厘散提取物为参照,对模型的精密度及与二维孔板模型的差异进行了考察,并对四个批次的昆明山海棠和复方七厘散提取物的肝毒性进行了评价,考察了方法的适用性。方法学考察结果显示,该模型的精密度和适用性良好,优于传统的二维孔板。接着,在三维肝细胞芯片模型上对不同样品给药3或7天的肝毒性进行了比较,发现中药成分的肝毒性随着给药时间的延长而增强。最后,对等生药量的单味中药昆明山海棠和复方中成药昆仙胶囊进行了肝毒性比较,发现中药配伍可以显著降低昆明山海棠的肝毒性。综上,本研究建立了一种高通量、稳定可靠的三维肝细胞芯片模型,可用于中药肝毒性的快速评价。
A high-throughput three-dimensional(3D)hepatocyte culture model is constructed in this study.It is capable of replicating the 3D in vivo environment and offers the advantages of high throughput,enhanced reproducibility,low cost,and simplified operation,rendering a valuable tool for hepatotoxicity screening of traditional Chinese medicine(TCM).First,we constructed the 3D high throughput liver chip model using collagen hydrogel.The precision and its difference with traditional cell culture plates were assessed using acetaminophen,Tripterygium hypoglaucum,and Qili San as the references.The feasibility of this model was also investigated by comparing the hepatotoxicity among four batches of T.hypoglaucum and Qili San.The methodology verification shows that the 3D hepatocyte model is better than traditional two-dimensional(2D)cell culture model in precision and feasibility.Subsequently,we compared the hepatotoxicity of different samples over a period of three or seven days and found that the hepatotoxicity of TCM extracts increased over time.Finally,we compared the hepatotoxicity of T.hypoglaucum and its compound formula Kunxian capsule under equivalent concentration.The results showed that the compound Kunxian capsule could significantly reduce hepatotoxicity of T.hypoglaucum.Generally,we constructed a high-throughput,robust 3D liver-on-a-chip model with the potential of rapid assessing TCM-induced liver toxicity.
作者
侯宇
吕恬
高照
屠鹏飞
艾晓妮
姜勇
HOU Yu;LÜTian;GAO Zhao;TU Peng-fei;AI Xiao-ni;JIANG Yong(State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191,China)
出处
《药学学报》
CAS
CSCD
北大核心
2024年第6期1787-1793,共7页
Acta Pharmaceutica Sinica
基金
山东省重点研发计划(2021CXGC010507)
国家重点研发计划项目(2023YFC3505000)
北京市自然科学基金(7222273)
中华中医药学会青年人才托举工程(2020-QNRC2-08).
关键词
肝脏芯片
三维肝细胞模型
中药肝毒性
高通量筛选
配伍减毒
liver-on-a-chip
3D hepatocyte model
hepatotoxicity of traditional Chinese medicine
high throughput screening
formulation for detoxification
