IL-6/STAT3信号通路对慢性胰腺炎ADM的调控作用及大柴胡汤的干预机制研究

胰腺纤维化是慢性胰腺炎（CP）的重要病理表现已成为普遍共识，但是伴随胰腺纤维化还可见到另一种病理现象，即腺泡细胞管状化生（ADM）。新近研究表明，ADM与胰腺癌癌前病变PanIN的分子表型相似，甚至认为ADM是比PanIN更早的胰腺癌早期事件。IL-6/STAT3信号通路在PanIN的形成中发挥重要作用，且有文献报道在CP和胰腺癌患者均可见到血清IL-6升高，那么，CP时升高的IL-6是否可通过STAT3信号通路调控ADM形成？本课题拟采用胰腺STAT3特异性敲除小鼠，分离腺泡细胞进行3D培养，研究IL-6/STAT3通路对ADM形成的影响。课题组前期研究发现大柴胡汤可以降低CP小鼠血清和胰腺IL-6水平、抑制胰腺纤维化，还可减少ADM形成，但是其机制不清。拟采用在体和离体实验，研究大柴胡汤是否通过调控IL-6/STAT3信号通路影响ADM形成，为大柴胡汤防治CP及其恶性进展提供实验依据。

Pancreatic fibrosis is the main pathological features of chronic pancreatitis(CP). Recent studies have found that another important pathological phenomenon can be observed during CP, which namely acinar to ductal metaplasia (ADM). Recent research shows that the molecular phenotype of ADM was similar to PanIN, and that ADM is an early event of pancreatic ductal adenocarcinoma which occurred earlier than PanIN. Serum IL-6 levels are increased in both CP and pancreatic cancer patients, and the IL-6/STAT3 signaling pathway is found to play an important role in the formation of PanIN. However, whether the elevated IL-6 in the micro-environment of CP can regulate ADM formation by STAT3 signal transduction is still unclear. In this study, pancreatic STAT3 specific knockout mice were used,.and acinar cells were isolated for 3D culture to study the effect of IL-6/STAT3 pathway on ADM formation. Previous research by the research team found that Dachaihu Decoction can reduce serum and pancreatic IL-6 levels in CP mice, inhibit pancreatic fibrosis, and reduce ADM formation, but the mechanism is unclear. We will use in vivo and in vitro experiments to study whether DaChaihu Decoction.affects ADM by regulating IL-6/STAT3 signaling pathway, and provides experimental evidence for prevention and treatment of CP and its malignant progression by Dachaihu Decoction.