从cAMP-PKA信号通路调控转运体AQP8/MRP2表达探讨利湿退黄法的作用机制

黄疸治疗大法为利湿退黄，但湿邪与黄疸之间的物质基础是什么？其作用机制不明确。肝脏的代谢产物是通过分布在肝细胞胆管侧细胞膜转运体来完成的，是黄疸最重要的发病机制。研究发现转运体AQP8与MRP2均分布于肝细胞胆管侧膜，黄疸“湿”与AQP8介导“水”转运导致胆汁排泄障碍密切相关；“黄”与MRP2介导胆红素代谢障碍紧密关联，共同作用信号通路为cAMP-PKA。课题组前期通过黄疸性肝炎模型发现转运体AQP8下调，给予茵陈治疗后上调。我们创新提出利湿退黄法中药-复方通过调节“胆道”的“水”转运使“胆红素”代谢以利湿退黄，正是通过cAMP-PKA信号通路调节AQP8/MRP2表达而发挥作用，本研究拟采用阻断剂、激动剂及细胞荧光探针标记技术观测AQP8/MRP2定位、定量及转运分布。冀以探索湿邪与黄疸之间的物质基础及“利湿退黄”法则作用机制，指导其法则对临床应用与研发。

Treatment of icterus is based on the dampness elimination and jaundice removal, nevertheless, what are the links between their material basis? The mechanisms remain unclear. Liver metabolites are distributed by cell membrane transporters in the lateral membrane of hepatocytes, which is the most important pathogenesis of jaundice. Researchers found that the transporter AQP8 and MRP2 were evenly distributed in the lateral membrane of hepatocytes, and the "dampness" of jaundice was closely related to the obstruction of bile secretion caused by AQP8-mediated "water" transport. "Yellow" is closely associated with MRP2-mediated bilirubin metabolism disorder, and the co-acting signaling pathway is cAMP-PKA. By using the artemisia treatment, down-regulated AQP8 transporters were found to be up-regulated by research group under icteric hepatitis model. An innovative approach using Traditional Chinese Medicine - Compound treatment for dampness elimination and jaundice removal through regulating the "biliary" "water" transport in order to metabolise the bilirubin is put forward by our team. This treatment is precisely instrumental for the expression of AQP8/MRP2 by regulating cAMP-PKA signaling pathway. in this research, the localization, quantitation and transport distribution of AQP8/MRP2 were observed by using blockers, agonists and fluorescent probe labeling techniques. We aim to search material basis between the links of dampness and jaundice, as well as the mechanisms of dampness elimination and jaundice removal method, also to guide the clinical application and medical.