基于线粒体解偶联机制的药物发现

1、科研项目
（1）国家自然科学基金委员会，面上项目，82170472， 硝唑尼特抗动脉粥样硬化作用及机制研究，2022-01-01至2025-12-31，55.00万元，在研，主持
（2）国家自然科学基金委员会，面上项目，50773014，聚癸二酸甘油醇酯弹性体作为药物植入缓释载体材料的基础研究，2008-01-01至2010-12-31，30万元， 已结题，主持
2、代表性科研成果
脂质代谢紊乱可导致包括高脂血症、动脉粥样硬化及代谢相关脂肪性肝病等多种疾病的发生。本课题组聚焦于线粒体解偶联剂的药理学研究，发现口服抗寄生虫药物硝唑尼特及其活性代谢物替唑尼特可诱导适度的线粒体解偶联效应，激活肝细胞AMPK信号。硝唑尼特口服途径用药能够抑制仓鼠和小鼠的实验性高脂血症和肝脂肪变性。本发现提示硝唑尼特可能成为一种新型抗高脂血症及肝脂肪样变的潜在临床药物。

1.Li, F.; Jiang, M.; Ma, M.; Chen, X.; Zhang, Y.; Zhang, Y.; Yu, Y.; Cui, Y.; Chen, J.; Zhao, H.; Sun, Z*.; Dong, D*. Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice. Acta Pharm Sin B. 2022;12(3):1322-1338. (IF: 14.9)
2.Hu, N.; Fu, Y.; Li, W.F.; Yang, X.R.; Cao, M.; Li, F.F.; Chen, J.H.; Chen, X.Y.; Zhao, H.; Sun, Z.J.;* Dong, D.L.* Chemical mitochondrial uncouplers share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation. Toxicol Appl Pharmacol. 2021; 414:115426. (IF:4.22)
3.Ma, R,; Ma, Z.G.; Gao, J.L.; Tai, Y.; Li, L.J.; Zhu, H.B.; Li, L.; Dong, D.L.; Sun, Z.J.* Injectable pegylated niclosamide (polyethylene glycol-modified niclosamide) for cancer therapy. J Biomed Mater Res A. 2020;108(1):30-38. (IF:3.525)
4.Ma,Z.G.; Ma,R.; Wang, X.; Gao, J.L.; Zheng, Y.F.; Sun, Z.J.*. Enzyme and PH responsive 5-flurouracil (5-FU) loaded hydrogels based on osalazine derivatives for colon-specific drug delivery. European Polymer Journal. 2019,118:64-70. (IF:3.62)
5.Ma, R.; Ma, Z.G.; Zhen, C.L.; Shen. X.; Li, S.L.; Li, L.; Zheng, Y.F.; Dong, D.L.; Sun, Z.J.*. Design, synthesis and characterization of poly (methacrylic acid-niclosamide) and its effect on arterial function. Mater Sci Eng C Mater Biol Appl. 2017;77:352-9. (IF:4.16)
6.Ma, Z.G.; Ma ,R.; Xiao, X.L.; Zhang, Y.H.; Zhang, X.Z.; Hu, N.; Gao, J.L.; Zheng, Y.F.; Dong, D.L.; Sun, Z.J.*. Azo polymeric micelles designed for colon-targeted dimethylfumarate delivery for colon cancer therapy. Acta Biomaterialia. 2016,44: 323-31. (IF:6.00)
7.Guo, X.L; Lu, X.L.; Dong, D.L.; Sun, Z.J*. Characterization and optimization of glycerol/sebacate ratio in poly(glycerol-sebacate) elastomer for cell culture application. J Biomed Mater Res A. 2014;102(11):3903-7. (IF:2.841)
8.Sun, Z. J.;* Sun, B.; Tao, R.B.; Xie, X.; Lu, X.L.; Dong, D.L*. A poly(glycerol-sebacate-curcumin) polymer with potential use for brain gliomas. J Biomed Mater Res A. 2013;101(1):253-60. (IF:2.8)
9.Sun, Z.J.;* Wu, L.; Huang, W.; Chen, C.; Chen, Y.; Lu, X.L.; Zhang, X.L.; Yang, B.F.; Dong, D.L.* Glycolic acid modulates the mechanical property and degradation of poly(glycerol, sebacate, glycolic acid). J Biomed Mater Res A. 2010;92(1):332-9. (IF:3.62)
10.Sun, Z.J.;* Chen, C.; Sun, M.Z.; Ai, C.H.; Lu, X.L.; Zheng, Y.F.; Yang, B.F.; Dong, D.L.* The application of poly (glycerol-sebacate) as biodegradable drug carrier. Biomaterials. 2009;30(28):5209-14. (IF:7.36)