药物/毒物诱导的中毒性肝损伤进程中肝组织损伤与修复并存。本课题前期发现，在多种中毒性肝损伤模型中，肝脏羟基类固醇硫酸基转移酶2B1(SULT2B1) 表达显著增高。本项目据前期工作提出：SULT2B1通过影响肝细胞增殖、星状细胞（HSCs）活化和卵圆细胞（HOCs）增殖分化在中毒性肝损伤修复中发挥重要作用。本项目拟首先，在DDC和TAA两种毒物诱导的肝损伤模型中尾静脉注射SULT2B1干扰/过表达慢病毒，研究SULT2B1对肝细胞增殖、HSCs活化、HOCs数目等的影响及机制；其次，利用小鼠肝细胞和HSCs共培养模型，研究DDC/TAA诱导肝细胞中SULT2B1增高对HSCs活化状况的影响及机制；最后，研究DDC/TAA诱导肝细胞/HOCs中SULT2B1增高对小鼠HOCs增殖分化的影响及机制。本课题将阐明SULT2B1在中毒性肝损伤修复中的作用及机制，为防治中毒性肝损伤提供新的作用靶点。

The occurrence of drug/toxin-induced liver injury is getting increasing recently. The dynamic interaction between liver injury and compensatory tissue repair plays a pivotal role in determining the ultimate outcome of hepatotoxicity initiated by drugs or toxins. Our previous work found the expression of hydrosteroid sulfotransferase SULT2B1 was dramatically upregulated in the liver of hepatotoxicity model induced by CCL4、ANIT、DDC and TAA. However, the role of SULT2B1 in the tissue repair during the drug/toxin-induced liver injury remains to be elucidated. Based on our previous study, we propose that SULT2B1 may regulate the progression of tissue repair in drug/toxin-induced liver injury by participating in the following three facets: the proliferation of hepatocytes, activation of fat storing stellate cells (HSCs) and the cell proliferation and differentiation of hepatic oval cells. To clarify the proposal, we design the following experiments. Firstly, Lenti-SULT2B1-siRNA and Lenti-SULT2B1 will be delivered into C57BL/6J mice with liver injury induced by DDA or TAA via tail vein injection. The cell proliferation of hepatocytes, the activation of HSCs and the number of HOCs will be detected. Secondly, the primary mouse hepatocytes and HSCs will be co-cultured. The effect of upregulated SULT2B1 induced by DDC/TAA in the hepatocytes on the activation of HSCs will be studied. The underlying mechanisms will be further explored. Thirdly, the effect of upregulated SULT2B1 induced by DDC/TAA in the hepatocytes or the primary hepatic oval cells on the cell proliferation and differentiation of hepatic oval cells will be investigated. The underlying mechanisms will be further explored. The present project will clarify the role of SULT2B1 in the tissue repair of the drug/toxin-induced liver injury, and then provide a novel target for treating drug/toxin-induced liver injury.