Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Med Sci Monit. 2018 Apr 16;24:2280-2286. doi: 10.12659/msm.909557.
BACKGROUND Inflammation plays an important role in initiation and development of severe acute pancreatitis (SAP). Curcumin exerts potent anti-inflammatory effects in many diseases, including acute pancreatitis. However, the specific molecular mechanisms are not clear. MATERIAL AND METHODS Intra-biliopancreatic duct injection of taurocholate was used to establish an animal model of SAP. Curcumin was administrated to animals as pre-treatments. Concentrations of cytokines in serum and ascites were measured by enzyme-linked immunosorbent assay (ELISA). A colorimetric method was used to determine the amylase activity. Western blotting was used to examine the expression levels and phosphorylation levels of proteins. Immunoprecipitation was used to assess the molecular association between apoptosis signal- regulating kinase 1 (ASK1) and thioredoxin (Trx). RESULTS Pre-treatment with curcumin reduced the concentrations of interleukin (IL6) and tumor necrosis factor (TNFα) in serum and ascites, as well as the ascites volume and amylase activity in SAP rats. Pre-treatment with curcumin reduced the expression level of TNF receptor-associated factor 1 (TRAF1), IL6, and TNFa in pancreas in SAP rats. Moreover, the phosphorylation levels of mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), MKK7, and c-Jun NH(2)-terminal protein kinase (JNK) were reduced by curcumin pre-treatment. The molecular association between ASK1 and Trx was recovered by curcumin pre-treatment. As a result, the nuclear translocation of nuclear factor kappa B (NF-κB) was suppressed in pancreases from SAP rats. CONCLUSIONS Activation of the TRAF1/ASK1/JNK/NF-κB signaling pathway is involved in the inflammation of SAP. Curcumin exerts anti-inflammatory effects by suppressing this proinflammatory pathway.
炎症在重症急性胰腺炎（SAP）的发生和发展中起着重要作用。姜黄素在许多疾病中具有强大的抗炎作用，包括急性胰腺炎。然而，具体的分子机制尚不清楚。
通过胆胰管内注射牛磺胆酸钠建立 SAP 动物模型。姜黄素作为预处理给予动物。采用酶联免疫吸附试验（ELISA）测定血清和腹水细胞因子浓度。比色法测定淀粉酶活性。Western blot 检测蛋白表达水平和磷酸化水平。免疫沉淀检测凋亡信号调节激酶 1（ASK1）和硫氧还蛋白（Trx）之间的分子关联。
姜黄素预处理降低了 SAP 大鼠血清和腹水中白细胞介素（IL6）和肿瘤坏死因子（TNFα）的浓度以及腹水体积和淀粉酶活性。姜黄素预处理降低了 SAP 大鼠胰腺中 TNF 受体相关因子 1（TRAF1）、IL6 和 TNFa 的表达水平。此外，姜黄素预处理降低了丝裂原活化蛋白激酶（MAPK）激酶 4（MKK4）、MKK7 和 c-Jun NH2-末端蛋白激酶（JNK）的磷酸化水平。姜黄素预处理恢复了 ASK1 和 Trx 之间的分子关联。结果，SAP 大鼠胰腺中核因子 kappa B（NF-κB）的核转位受到抑制。
TRAF1/ASK1/JNK/NF-κB 信号通路的激活参与了 SAP 的炎症反应。姜黄素通过抑制这条促炎途径发挥抗炎作用。
