ICP胎儿缺氧机制不清，前期研究发现ICP胎盘血流储备功能受损、绒毛血管舒缩调节异常、CRH多肽转录和翻译水平在缺氧应激时失代偿呈低表达，提示缺氧应激时胎盘血管微环境发生改变。预实验发现ICP循环外泌体miR-767-3p表达下调，胎盘组织TGF-β和pSMAD2低表达，生物信息分析发现miR-767-3p可靶向调控SMAD2。因此我们提出循环外泌体miR-767-3p靶向调控TGF-β/SMAD2/VEGF通路，导致胎盘绒毛血管容积变窄和血氧储备下降，诱发胎儿缺氧。将研究重点聚焦在循环外泌体miRNA细胞间信号转导，创新性应用胎盘组织血管体视学研究胎盘单位血管微环境变化与VEGF表达相关性，通过动物及细胞水平进行功能机制验证，阐明miR-767-3p对TGF-β/SMAD2靶向调控及下游信号通路对胎盘单位血管微环境的调控机制，为ICP胎儿缺氧的病理生理机制研究提供新的思路和切入点。

The specific mechanism of fetal hypoxia in the intrahepatic cholestasis of pregnancy (ICP) is unclear. Our previous studies indicated that the function of blood reserve in ICP is impaired, the regulation of villi vasomotor is abnormal and the transcription and translation levels of CRH polypeptide are disrupted, suggesting that the microenvironment of placental vascular changes during fetal hypoxic stress in ICP. Preliminary experiments we have found that the expression of miR-767-3p derived from circulating exosomes that could target the SMAD2 was down-regulated and the protein expression of TGF-β and pSMAD2 in the placental tissues were down-regulated. We assumed that circulating exosome miR-767-3p derived from circulating exosomes targeted regulation of the TGF-β/SMAD2/VEGF signaling pathway, resulting in narrowed blood vessel volume of placental villi and decreased blood oxygen reserve of the placenta, inducing fetal hypoxia. Human samples are used to proven miR-767-3p targeted regulate TGF-β/SMAD2/VEGF signaling pathway, then placenta body approach is applied to study the placenta unit vascular microenvironmental changes and the correlation of VEGF expression, and then we want to illustrate the TGF-β/SMAD2 downstream signaling pathways and regulatory mechanism of the vascular microenvironment of placenta units of ICP on function mechanism research through the animal and cell level. These findings will provide a new direction for the pathophysiology mechanism of ICP fetal hypoxia research in the future.