基于美洲大蠊提取物调控肝脏免疫微环境抑制HSC的抗肝纤维化分子机制研究

研究证实，肝星状细胞（HSC）活化是慢性肝损伤向肝纤维化（HF）发展的重要病理机制。课题组前期研究表明，美洲大蠊提取物（PA-B）可促进HSC凋亡，具有良好的抗肝损伤、抗HF活性，并可调节CD4+/CD8+的平衡，但其免疫调节作用是否为PA-B抗HF机制之一，有待深入研究。课题将结合细胞、动物模型，围绕“免疫活化-HSC凋亡”的问题，开展以下研究。①构建HF模型，给予PA-B干预，探究其对肝脏免疫细胞的影响及对细胞因子的作用，以及对HSC凋亡的影响；②与含药血清共孵育KCs/HSC、NK/HSC，探究PA-B对HSC、KCs、NK等细胞、细胞因子、趋化因子的影响，以及促进活化HSC凋亡的主要机制。通过研究，阐明“PA-B-肝脏免疫微环境-免疫细胞-细胞因子-HSC-HF”之间的网络关系，揭示美洲大蠊基于免疫调节防治HF的新机制，为寻找安全、有效、经济的抗HF新药及动物源免疫调节剂奠定基础。

Research have confirmed that activation of hepatic stellate cells (HSC) is an important pathological mechanism for the development of chronic hepatic injury into hepatic fibrosis (HF). Our previous research have shown that Periplaneta Americana extract (PA-B) can promote the apoptosis of HSC, has good anti-HF effect and anti-liver injury activities, and has the effect of regulating CD4 + / CD8 +. However, whether its immune regulatory function is one of the anti-HF mechanisms of PA-B remains to be further studied. The following studies will be conducted on the relationship between “immune activation-hsc apoptosis ” in combination with cell and animal models.①HF models will be constructed and given PA-B intervention to explore its effects on live immune cells and cytokines, as well as on the apoptosis of HSC.②KCs/HSC and NK/HSC will be co-incubated with drug-containing serum to explore the influence of PA-B on HSC, KCs, NK and other cells, cytokines and chemokines, and the main mechanism to promote the apoptosis of activated HSC. Through the research, the network relationship between “PA-B - liver immune microenvironment - immune cells - cytokines - HSC-HF” will be clarified , and the new mechanism of prevention and treament HF that based on immune regulation of Periplaneta Americana will be revealed, which will lay a foundation for the search for new anti-HF drugs and animal oriain immunomodulator with safe, effective and economical.