Yao Guo-Wang, Li Cai-Xia, Fan Yu-Xing, Zhuo Yu-Zhen, Zhang Shu-Kun, Cui Li-Hua
Department of Gastrointestinal Surgery, Hospital of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, 300100, China.
J Nat Med. 2025 May;79(3):706-720. doi: 10.1007/s11418-025-01901-x. Epub 2025 Apr 3.
Chronic pancreatitis (CP) is a progressive disease characterized by injury on pancreatic acinar cells (PACs), ongoing fibrosis, and gradual loss of exocrine and endocrine functions. Sphingosine kinase 1 (SK1) expression is elevated in injured PACs, and its metabolite sphingosine-1-phosphate (S1P) promotes the activation of pancreatic stellate cell (PSC) through autophagy and pyroptosis. Chaihu Guizhi Ganjiang Decoction (CGGD), a traditional Chinese medicine is widely used in the clinical treatment of digestive diseases. However, whether CCGD affects the SK1/S1P axis and relieves pancreatic damage through this pathway remains unknown. In this study, CP rats were treated with CGGD, individually or in combination with S1P and SKI-178 for four weeks to assess the effect of CGGD on pancreatic injury, fibrosis, autophagy and pyroptosis. The results showed that SK1, S1P and S1PR2 levels were increased in the pancreatic tissues of CP rats, while CGGD reduced these levels. Treatment with S1P exacerbated histological damage, promoted fibrosis, accelerated autophagy, and induced pyroptosis. Conversely, SKI-178 suppressed these effects. Notably, CGGD mitigated histological damage, decreased serum amylase and lipase levels, and alleviated pancreatic fibrosis induced by S1P. Furthermore, CGGD downregulated autophagy and pyroptosis induced by S1P, exhibiting an effect comparable to SKI-178 in CP. In conclusion, CGGD ameliorates pancreatic damage by reducing fibrosis, inhibiting autophagy, and suppressing pyroptosis through the SK1/S1P axis.
慢性胰腺炎（CP）是一种进行性疾病，其特征是胰腺腺泡细胞（PACs）损伤、持续性纤维化以及外分泌和内分泌功能逐渐丧失。鞘氨醇激酶1（SK1）在受损的PACs中表达升高，其代谢产物鞘氨醇-1-磷酸（S1P）通过自噬和细胞焦亡促进胰腺星状细胞（PSC）的激活。柴胡桂枝干姜汤（CGGD）是一种中药，广泛应用于消化系统疾病的临床治疗。然而，CGGD是否影响SK1/S1P轴并通过该途径减轻胰腺损伤尚不清楚。在本研究中，将CP大鼠单独或联合S1P和SKI-178用CGGD治疗4周，以评估CGGD对胰腺损伤、纤维化、自噬和细胞焦亡的影响。结果显示，CP大鼠胰腺组织中SK1、S1P和S1PR2水平升高，而CGGD降低了这些水平。用S1P治疗加剧了组织学损伤，促进了纤维化，加速了自噬，并诱导了细胞焦亡。相反，SKI-178抑制了这些作用。值得注意的是，CGGD减轻了组织学损伤，降低了血清淀粉酶和脂肪酶水平，并减轻了S1P诱导的胰腺纤维化。此外，CGGD下调了S1P诱导的自噬和细胞焦亡，在CP中表现出与SKI-178相当的效果。总之，CGGD通过SK1/S1P轴减少纤维化、抑制自噬和抑制细胞焦亡来改善胰腺损伤。
