中文摘要
胰腺星状细胞(PSC)活化是慢性胰腺炎(CP)胰腺纤维化的核心事件,近来的研究发现,PSC活化的同时伴随胰腺大量巨噬细胞(Mφ)浸润。最新研究表明:Mφ在CP进展中发生了极化偏移,且与胰腺纤维化相关,但是极化的Mφ对胰腺纤维化的确切影响和调控机制尚不清楚。拟采用Dil标记的不同极化状态Mφ尾静脉注射回输至SCID小鼠体内,及Mφ-PSC非接触性共培养体系,结合流式细胞、Luminex等技术,研究不同极化状态Mφ对PSC活化的调控作用,及对胰腺纤维化的影响,明确致PSC活化的“Mφ主凶”,阐明“通过调控Mφ极化稳态改善胰腺纤维化”的理论,为CP防治提供全新策略。大柴胡汤治疗CP疗效确切,但抗胰腺纤维化的机制不清。拟通过在体和离体实验,研究大柴胡汤是否通过调控Mφ的极化稳态,进而减轻PSC活化、抑制胰腺纤维化,阐明大柴胡汤防治胰腺纤维化的分子机制,为其在CP的临床应用提供实验依据。
英文摘要
Activation of pancreatic stellate cells (PSC) is the central event of the pancreatic fibrosis in chronic pancreatitis (CP). In recent years, the studies found PSC activation accompanied large numbers of macrophages (Mφ) infiltration in pancreatic tissue during the development of CP. What is the role of these macrophages in PSC activation and pancreatic fibrosis?The latest research shows that macrophage polarization can be seen in the pancreatic fibrosis. The numbers of M2 macrophages is proportional to pancreatic fibrosis, but the influence and mechanism of macrophages polarization on pancreatic fibrosis is not known. We intend to transfuse the different polarization of macrophage(M1 macrophage and M2 macrophage) labeled with DIL to SCID mice from tail vein directly and use the co-culture system of macrophages and PSC, as well as the techniques of flow cytometry and Luminex to explore the role of macrophage polarization in the activation of PSC and pancreatic fibrosis, to search the key targets induced PSC activation. We hope to verify the theory that the regulation of macrophage polarization is a measure to improve pancreatic fibrosis and provide a new strategy for the prevention and treatment of CP. .Furthermore, Dachaihu Decoction is a classic prescription for restraining inflammatory response. The effect of Dachaihu Decoction on pancreatic fibrosis is confirmed, but its mechanism is unclear. By vivo and vitro experiments, we intend to research whether Dachaihu Decoction regulate the polarization of macrophages or promote polarized macrophages transformed well, thereby reducing PSC activation and inhibiting pancreatic fibrosis. We hope to elucidate the molecular mechanism of Dachaihu Decoction treating pancreatic fibrosis, and provide the support for clinical application of Dachaihu Decoction in CP.
