补肾祛湿中药治疗ICP的内质网应激分子机制探讨

We have confirmed that kidney-tonifying and dampness-expelling Chinese herbal medicine YHHJ was effective in treating ICP, and had obtained a patent. In the previous study we found that YHHJ can alleviate ER stress in estrogen-induced ICP. The results suggest that the effect of YHHJ in treating ICP may mediated through blocking ER stress, inhibiting hepatocyte apoptosis. In the present study, we are prepare to further investigate the relationship among high levels of estrogen, ER stress, and ICP. The experiment will use ER stress specific agonists and inhibitors to certify the ER stress phenomenon in ICP. Furthermore, rescuing experiment method were used to demonstrate the potential mechanism of YHHJ in regulating ER stress mediated hepatocyte apoptosis. At the same time, the function of YHHJ in treating ICP were studied in estrogen-induced ICP rats. The destination of the research was perfect, and if the project was funded we will supply much and better evidence of YHHJ in treating ICP. Therefore, we believe that the study will provide important clinical value.

茵黄合剂是我院基于补肾安胎、祛湿利胆法自创的一种补肾祛湿中药复方，临床治疗妊娠期肝内胆汁淤积症（ICP）疗效显著，已获专利保护。前期发现，ICP大鼠肝脏/肝细胞中有明显的内质网应激（ERS）现象；茵黄合剂含药血清可逆转内质网应激、修复肝细胞损伤，其机制可能与茵黄合剂阻断ERS、抑制肝细胞凋亡有关。研究拟应用内质网应激抑制剂/激动剂，从正反两方面论证补肾祛湿中药通过调控ERS修复肝细胞损伤的作用与机制；通过ICP大鼠模型的在体研究，进一步评估补肾祛湿中药治疗的作用机制；在临床样本中通过评价补肾祛湿中药、ERS、ICP之间的关系，获得其临床支持依据。用于ICP治疗的茵黄合剂与ERS的关系未见报道，本研究将为传承中药茵黄合剂的临床应用提供更多有用的理论依据。

茵黄合剂是我院基于补肾安胎、祛湿利胆法自创的一种补肾祛湿中药复方，临床治疗妊娠肝内胆汁淤积症（ICP）疗效显著，已获专利保护。本研究应用内质网应激抑制剂/激动剂，采用体内、外实验相结合的研究方法，从正、反两方面研究发现，茵黄合剂可通过调控内质网应激相关蛋白CHOP、GRP78、IRE1、PERK和ATF6的表达，修复雌激素诱导肝内胆汁淤积肝细胞的损伤，并且通过临床试验证实茵黄合剂对ICP的治疗作用与其缓解ICP患者的内质网应激状态相关。本研究为传承中药复方茵黄合剂的临床应用提供了更多有用的理论依据。