目的

探索慢性胰腺炎(CP)的发病机制,检测验证慢性胰腺炎、肠道菌群以及免疫炎症因子之间的关系,为CP 的病因研究提供更丰富的数据支持。

方法

第一部分:招募2023 年1 月至2024 年12 月包头医学院第二附属医院就诊患者,按标准纳入实验组(CP 患者)与对照组(健康体检者),收集患者粪便行16S rRNA 测序,血清用ELISA 检测IL -6、IL-8、IL-1β、肿瘤坏死因子-α(TNF-α) 和核因子-κB p65(NF-κB p65)等炎症因子,对比分析CP 患者与正常人肠道菌群及炎症因子差异。 第二部分:应用二丁基二氯化锡(DBTC)建造CP 大鼠模型,分为实验组(CP 模型)和对照组(空白对照),并将DBTC 分为1.6 mg·kg ^-1高浓度、0.8 mg·kg ^-1 低浓度,分别注射,留取粪便和血液标本进行检测。

结果

CP 患者与健康对照组存在明显的菌群差异,表现为有益菌减少,致病菌增加。CP 组血清IL -6 (P <0.05)、IL-8(P <0.01)、IL-1β(P <0.001)、NF-κB p65(P <0.01)高于对照组,对照组TNF-α(P <0.001)高于CP 组。 同时CP 大鼠模型实验粪便检测结果与人类相近,血液中NF-κB p65、IL-1β、IL-8、TNF-α 含量显著高于对照组(P <0.0001),IL-6(P <0.01)也高于对照组。

结论

研究表明慢性胰腺炎和肠道菌群紊乱以及免疫因子升高有关,并进一步提出肠道菌群通过IL-1β/NF-κB p65 信号通路调控CP 的假设,同时明确了高剂量DBTC 建造的CP 大鼠模型更具稳定性,为后续研究提供依据。

Objective

To investigate the pathogenesis of chronic pancreatitis (CP), validate the relationship between CP, gut microbiota,and immune-inflammatory factors,and provide more comprehensive data support for the study of CP etiology.

Methods

Part 1:Patients admitted to the Second Affiliated Hospital of Baotou Medical College from January 2023 to December 2024 were recruited and divided into an experimental group (CP patients) and a control group (healthy individuals) based on predefined criteria.Fecal samples were collected for 16S rRNA sequencing, and serum levels of inflammatory factors, including IL-6,IL-8,IL-1β, tumor necrosis factor-α (TNF-α),and nuclear factor-κB p65 (NF-κB p65), were measured using ELISA. Differences in gut microbiota and inflammatory factors between CP patients and healthy controls were analyzed. Part 2: A dibutyltin dichloride (DBTC)-induced CP rat model was established, with rats divided into an experimental group (CP model) and a control group (blank control).DBTC was administered at high (1.6 mg·kg ^-1) and low (0.8 mg·kg ^-1) concentrations, respectively.Fecal and blood samples were collected for testing.

Results

Significant differences in gut microbiota were observed between CP patients and healthy controls, characterized by a decrease in beneficial bacteria and an increase in pathogenic bacteria.Serum levels of IL-6 (P <0.05), IL-8 (P <0.01),IL-1β (P <0.001),and NF-κB p65 (P <0.01) were higher in the CP group than in the control group,whereas TNF-α (P <0.001) was higher in the control group. Similarly,fecal test results in the CP rat model were consistent with human findings, and blood levels of NF-κB p65,IL-1β,IL-8,and TNF-α were significantly higher in the experimental group than in the control group (P <0.0001),with IL-6 (P <0.01) also elevated.

Conclusion

The study demonstrates that chronic pancreatitis is associated with gut microbiota dysbiosis and elevated immune-inflammatory factors. Furthermore,it proposes the hypothesis that gut microbiota regulates CP through the IL-1β/NF-κB p65 signaling pathway. Additionally,the high-dose DBTC-induced CP rat model was found to be more stable,providing a basis for future research.