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Int J Biol Sci 2019; 15(5):973-983. doi:10.7150/ijbs.30013

Research Paper

A Comprehensive Study of High Cholesterol Diet-Induced Larval Zebrafish Model: A Short-Time In Vivo Screening Method for Non-Alcoholic Fatty Liver Disease Drugs

Ji Ma1,2,3*, Hongli Yin1,2,3*, Maoru Li1,2,3*, Yang Deng1,2,3, Owais Ahmad4, Guohong Qin1,2,3, Qiangqiang He5, Jiajing Li1,2,3, Kai Gao6, Junyi Zhu1,2,3, Bing Wang1,2,3, Susu Wu1,2,3, Tao Wang7✉, Jing Shang1,2,3,5✉

1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China;
2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;
3. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, China;
4. School of life sciences, China Pharmaceutical University, Nanjing 211198, China;
5. Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, Qinghai Province, China;
6. Nanjing Ruiying Runze Biopharmaceutical Technology Co., Inc, Nanjing 210000, China;
7. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
*These three authors contributed equally to this work.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world. However, there is still no drug for NAFLD in the market, the study of potential therapeutic drugs on NAFLD is extraordinarily pressing and urgent. The rodent models for NAFLD drugs' study are always with a long time cost. Therefore, we aim to establish a short-time NAFLD drug screening model. A laboratory-made high cholesterol diet was used on larval zebrafish for 3 weeks to establish the NAFLD screen model. Lipid metabolism, oxidant stress, and pathology were studied to comprehensively demonstrate the whole spectrum of NAFLD on this model. Bezafibrate and pioglitazone were used to evaluate the model. Moreover, mechanism research was performed on this model.The NAFLD larval zebrafish model was established with the comprehensive process of NAFLD. Moreover, multiple index on lipid metabolism, oxidant stress, hepatic steatosis, and hepatic inflammation can be easily tested for drug screening. Furthermore, this model can be used to perform the mechanism research by testing mRNA expression. The NAFLD larval zebrafish model is a comprehensive short-time screening method for NAFLD drugs.

Keywords: non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, larval zebrafish, high cholesterol diet

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Ma J, Yin H, Li M, Deng Y, Ahmad O, Qin G, He Q, Li J, Gao K, Zhu J, Wang B, Wu S, Wang T, Shang J. A Comprehensive Study of High Cholesterol Diet-Induced Larval Zebrafish Model: A Short-Time In Vivo Screening Method for Non-Alcoholic Fatty Liver Disease Drugs. Int J Biol Sci 2019; 15(5):973-983. doi:10.7150/ijbs.30013. Available from http://www.ijbs.com/v15p0973.htm