母婴传播是我国进一步降低乙肝感染率的关键。胎盘感染是宫内传播的最重要途径。NTCP作为HBV感染的受体已逐步得到共识，IL-6可影响NTCP介导的HBV感染。我们先前证明胎盘表达NTCP及IL-6，血清IL-6水平与HBV宫内感染具有相关性，据此假设NTCP可介导HBV胎盘感染及细胞间感染，IL-6通过调节NTCP表达、膜转位而影响乙肝宫内传播。本课题拟①在组织、细胞及基因SNP水平证明NTCP在HBV感染胎盘中的作用；②采用活细胞标记及TC-FlAsH/ReAsH染色标记系统观察NTCP介导的HBV细胞间感染；③探讨IL-6对胎盘NTCP表达的调节，采用NTCP膜内外双标记表达质粒检测IL-6/PKC对NTCP膜转位、受体功能的调节。藉此初步阐明NTCP在HBV感染胎盘、宫内传播中作用及调节机制，丰富乙肝宫内传播的理论，寻找可能的影响因素，为制定新的以NTCP为靶点的干预模式提供依据。

Mother-to-infant transmission is still reported as the bottleneck for further reducing HBV infection in China. As crucial barrier between mother and fetus, placenta infected with HBV has been considered as one important route of HBV intrauterine transmission. NTCP has been proved to be an essential receptor for HBV infection; additionally IL-6 can influence HBV infection via inhibiting NTCP expression. During our previous study, expression of NTCP and IL-6 in placenta has been confirmed; an association of serum IL-6 level with HBV intrauterine infection has been displayed. We speculated that NTCP mediate HBV infection in placenta and cell-cell contact transfer and IL-6 regulate HBV intrauterine transmission via influencing NTCP expression and membrane translocation. To clarify those hypotheses, the following works will be carried out in this program, 1) to confirm the NTCP function in HBV infection and intrauterine transmission on three levels of placenta tissue, primary cells and singlenueleotide polymorphism; 2) exploiting fluorescent living cell tracker (CMFDA/PKH26) and the membrane-permeant fluorogenic biarsenicals FlAsH/ReAsH-EDT2 labeling system, to observe the cell-cell contact transfer of HBV and obtain 3D image; 3) with expression plasmid of NTCP with two-terminal labels and confocal microscopy, to investigate regulation of IL-6 on expression and membrane translocation of NTCP, as well as influence on HBV infection. With current program, we will identify the underlying function and regulatory mechanism of NTCP on HBV infection in placenta, which will expand our views about intrauterine transmission, help looking for influencing factors and provide potential intervention model targeting NTCP.