COMP通过CD36/MAPK通路调控PSCs活化参与慢性胰腺炎纤维化的机制研究

胰腺纤维化是慢性胰腺炎（CP）最重要的病理学特征之一，胰腺星状细胞（PSCs）活化在其中发挥关键作用。近期有研究表明软骨寡聚基质蛋白（COMP）能影响胶原蛋白的分泌，参与肺、肝等脏器的纤维化。预实验发现CP小鼠胰腺组织与活化的PSCs内COMP呈高表达，提示其可能是胰腺纤维化的标志物。本项目采用ELISA、qRT-PCR、WB、IHC、IF等比较CP患者与健康人群血清、CP与正常胰腺组织、静息和活化PSCs内COMP的表达水平，然后通过AAV病毒载体调控PSCs内COMP的表达，采用WB、IHC、IF分析其对细胞活化的影响，通过WB观察CD36/MAPK通路主要成员的总蛋白及磷酸化蛋白表达的变化，最后通过CP小鼠腹腔注射AAV病毒来调控胰腺内COMP的表达，以探索COMP作为CP治疗靶点的可行性。本研究旨在进一步阐明胰腺纤维化的发生机制，为抑制胰腺纤维化提供新的治疗靶点，以改善CP的预后。

Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP), and the activation of pancreatic stellate cell (PSCs) plays a key role in pancreatic fibrosis. Recent studies indicated that cartilage oligomeric matrix protein (COMP) could affect the secretion of collagen and participate in the fibrosis of lung, liver and other organs. Our preliminary study showed that COMP was highly expressed in pancreatic tissue of CP mice and activated PSCs, suggesting that COMP may be a marker of pancreatic fibrosis. In this project, ELISA, qRT-PCR, WB, IHC and IF were used to compare the expression levels of COMP in serum of CP patients and healthy people, CP tissue and normal pancreatic tissue, resting and activated PSCs. AAV virus vector was performed to regulate the expression of COMP in PSCs to analyze its effect on cell activation through WB, IHC and IF, and then WB was used to observe the change of total protein and phosphorylated protein levels of major members of CD36/MAPK pathway. Finally, the expression of COMP in pancreas was regulated by intraperitoneal injection of AAV into CP mice to explore the feasibility of COMP as a therapeutic target for CP. The purpose of this study is to further elucidate the pathogenesis of pancreatic fibrosis and provide a new therapeutic target for inhibiting pancreatic fibrosis, so as to improve the prognosis of CP.