探讨趋化因子CXCL12/CXCR4信号通路在慢性胰腺炎（CP）炎症和疼痛中的作用，以期为该疾病的治疗提供新的靶点。

72只SD大鼠随机分为4组（每组18只）：对照组（生理盐水处理），CP模型组（TNBS诱导），CP模型＋溶剂处理组，CP模型＋AMD3100处理组。通过胰腺壁内注射三硝基苯磺酸（TNBS）诱导CP，采用冯·弗雷测痛纤维丝试验评估SD大鼠胰腺超敏反应。通过Western blot和PCR分析检测大鼠胰腺中CXCL12和CXCR4的表达情况。HE染色观察胰腺组织病理学，免疫组织化学检测P物质和降钙素基因相关肽（CGRP）的表达情况。

TNBS注射3周后，CXCL12和CXCR4在大鼠胰腺中显著上调，CXCL12 mRNA水平增加了2倍（P<0.05），CXCL12蛋白表达水平也显著增加（P<0.05）。HE染色显示，TNBS注射增加了胰腺水肿、炎症和坏死的程度。免疫组织化学染色显示，TNBS处理后P物质和CGRP的表达水平显著增加（P<0.05）。细胞膜红色荧光探针标记技术显示CXCR4是CXCL12受体，在胰腺特异性背根神经节神经元上表达。使用CXCR4拮抗剂AMD3100靶向抑制CXCL12信号通路后，大鼠的疼痛敏感性显著降低，表现为对冯·弗雷纤维丝刺激的阳性反应频率显著减少（P<0.05）。此外，AMD3100处理后，胰腺中P物质和CGRP的表达水平显著下降（P<0.05），胰腺组织的病理损伤也明显改善，表现为炎症细胞浸润减少和腺泡结构的恢复。

CXCL12/CXCR4信号通路在CP的炎症和疼痛中起着重要作用。通过抑制CXCL12信号通路，使用CXCR4拮抗剂AMD3100能够显著减轻胰腺炎症、降低疼痛敏感性，并改善胰腺组织的病理损伤。CXCL12/CXCR4信号通路可能成为慢性胰腺炎治疗的一个潜在靶点，为进一步的研究和临床应用提供了科学依据。

To research the role of the CXCL12/CXCR4 signaling pathway in inflammation and pain associated with chronic pancreatitis (CP), aiming to provide new therapeutic targets for the disease.

A total of 72 SD rats were randomly divided into 4 groups (18 rats in each group): control group (saline treatment); CP model group (TNBS induced); CP model+solvent treatment group; CP model+AMD3100 treatment group. CP was induced by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Von Frey filaments were used to assess the pancreatic hyperalgesia in rats. The expression levels of CXCL12 and CXCR4 in the rat pancreas were analyzed using Western blot and PCR. HE staining was used to observe the histopathology of pancreatic tissue, and the expressions of substance P (SP) and calcitonin gene-related peptide (CGRP) was detected via immunohistochemistry.

Three weeks after TNBS injection, the expressions of CXCL12 and CXCR4 in the rat pancreas significantly increased, with CXCL12 mRNA levels doubling (P<0.05) and CXCL12 protein expression also significantly rising (P<0.05). HE staining revealed that TNBS injection exacerbated pancreatic edema, inflammation, and necrosis. Immunohistochemical findings indicated that the expression of SP and CGRP significantly increased after TNBS treatment (P<0.05). DIL labeling techniques confirmed that CXCR4, as the receptor for CXCL12, was expressed on specific dorsal root ganglion (DRG) neurons in the pancreas. When the CXCL12 signaling pathway was inhibited using CXCR4 antagonist AMD3100, the pain sensitivity in rats significantly decreased, as shown by a marked reduction in the frequency of positive responses to von Frey filament stimuli (P<0.05). Additionally, after AMD3100 treatment, the expression of SP and CGRP in the pancreas notably declined (P<0.05), and the pathological damage to the pancreatic tissue was clearly mitigated, characterized by a decrease in inflammatory cell infiltration and the restoration of acinar structure.

The CXCL12/CXCR4 signaling pathway plays an important role in the inflammation and pain of chronic pancreatitis (CP). By inhibiting the CXCL12 signaling pathway, the use of the CXCR4 antagonist AMD3100 can effectively alleviate pancreatic inflammation, reduce pain sensitivity, and improve the pathological damage of the pancreatic tissue. The CXCL12/CXCR4 signaling pathway may serve as a potential therapeutic target for chronic pancreatitis, offering a scientific foundation for further research and clinical application.