1. 毕业设计（论文）的内容和要求

肝星状细胞活化是肝脏纤维化的最重要特征和步骤，本课题通过构建肝星状细胞特异性启动子加荧光蛋白基因的质粒，在斑马鱼胚胎期进行显微注射并后续饲养，初步建立由绿色荧光标记肝星状细胞的瞬时转基因斑马鱼系，该斑马鱼系经过后续筛选及培养，可作为肝纤维化研究的重要工具。

　 本课题对学生所学知识和技能的要求： 1. 掌握科研文献查阅的方法，能够初步设计实验思路及技术路线； 2. 掌握基础的实验技能，并培养良好的科研习惯； 3. 能够独立阐述课题内容、撰写科研报告及中文论文。

2. 参考文献

1: Yin C, Evason KJ, Maher JJ, Stainier DY. The basic helix-loop-helix transcription factor, heart and neural crest derivatives expressed transcript 2, marks hepatic stellate cells in zebrafish: analysis of stellate cell entry into the developing liver. Hepatology. 2012 Nov;56(5):1958-70. 2: Hetherington AM, Sawyez CG, Borradaile NM. Microarray data and pathway analyses for primary human activated hepatic stellate cells compared to HepG2 human hepatoma cells. Data Brief. 2016 Dec 13;10:385-389. 3: Koyama Y, Brenner DA. Liver inflammation and fibrosis. J Clin Invest. 2017 Jan 3;127(1):55-64. 4: Bian EB, Wang YY, Yang Y, Wu BM, Xu T, Meng XM, Huang C, Zhang L, Lv XW, Xiong ZG, Li J. Hotair facilitates hepatic stellate cells activation and fibrogenesis in the liver. Biochim Biophys Acta. 2016 Dec 13;1863(3):674-686. 5: He P, Yu ZJ, Sun CY, Jiao SJ, Jiang HQ. Knockdown of HIPK2 attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-β1. Biomed Pharmacother. 2017 Jan;85:575-581. 6: Zhang F, Zhang M, Wang A, Xu M, Wang C, Xu G, Zhang B, Zou X, Zhuge Y. TWEAK increases SIRT1 expression and promotes p53 deacetylation affecting human hepatic stellate cell senescence. Cell Biol Int. 2016 Nov 26. 7: Liu J, Li M, Gong J, Han P, Wang Y, Tian D, Liao J. Knockdown of histidine-rich calcium binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells. Biol Open. 2016 Nov 23. 8: Ceni E, Mello T, Polvani S, Vasseur-Cognet M, Tarocchi M, Tempesti S, Cavalieri D, Beltrame L, Marroncini G, Pinzani M, Milani S, Galli A. The orphan nuclear receptor COUP-TFII coordinates hypoxia-independent proangiogenic responses in hepatic stellate cells. J Hepatol. 2016 Nov 17. 9: Zeng XY, Zhang YQ, He XM, Wan LY, Wang H, Ni YR, Wang J, Wu JF, Liu CB. Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster. Oncotarget. 2016 Nov 15. 10: Deng X, Deng L, Wang P, Cheng C, Xu K. Post#8209;translational modification of CREB#8209;1 decreases collagen I expression by inhibiting the TGF#8209;β1 signaling pathway in rat hepatic stellate cells. Mol Med Rep. 2016 Dec;14(6):5751-5759. 11: Cai SP, Cheng XY, Chen PJ, Pan XY, Xu T, Huang C, Meng XM, Li J. Transmembrane protein 88 attenuates liver fibrosis by promoting apoptosis and reversion of activated hepatic stellate cells. Mol Immunol. 2016 Dec;80:58-67. 12: Chen L, Brigstock DR. Integrins and heparan sulfate proteoglycans on hepatic stellate cells (HSC) are novel receptors for HSC-derived exosomes. FEBS Lett. 2016 Dec;590(23):4263-4274. 13: Schumacher JD, Guo GL. Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth Factors. Biomed Res Int. 2016;2016:8323747.

3. 毕业设计（论文）进程安排

2017.02.19-2017.03.01 撰写实施方案, 进行开题报告; 2017.03.02-2017.04.01 克隆HSC特异调控序列，连入GFP质粒中并进行; 2017.04.02-2017.05.01 显微注射并观察鉴定; 2017.05.02-2017.06.01 撰写毕业论文, 答辩。