2′,4′,6′-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury
2′,4′,6′-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury
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DOI：
10.1152/ajpgi.00210.2010
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发表时间：
2011-10-01
影响因子：
4.5
通讯作者：
Park, Sung-Joo
中科院分区：
文献类型：
--
作者：
Kim, Tae-Hyeon;Bae, Gi-Sang;Park, Sung-Joo
金天辉，裴桂生，吴海杰，金明生，朴基昌，具宝生，金宝杰，杨玉生，朴德娥，李建辉，徐世伟，申玉奎，尹坤杰，孙德辉，金海杰，苏海生，朴仁奎，宋海杰，朴世杰。2',4',6'-Tris（甲氧基甲氧基）查尔酮（TMMC）可减轻蓝蛋白诱导的急性胰腺炎及相关肺损伤的严重程度。[J] .中国生物医学工程学报，2011,31(5):693 - 694。首次发表于2011年7月21日；doi: 10.1152 / ajpgi.00210.2010。急性胰腺炎（acute pancreatitis， AP）是一种涉及腺泡细胞损伤和炎症细胞因子快速产生和释放的炎症性疾病，炎症细胞因子在局部胰腺炎症和全身并发症中起主导作用。2',4',6'-三（甲氧基甲氧基）查尔酮（TMMC）是一种人工合成的查尔酮衍生物，具有很强的抗炎作用。因此，我们旨在研究TMMC是否会影响小鼠AP和胰腺炎相关肺损伤的严重程度。我们采用冠状蛋白过度刺激AP模型。通过组织学分析和中性粒细胞隔离测定冠状蛋白注射小鼠胰腺炎的严重程度。TMMC预处理小鼠可降低AP和胰腺炎相关肺损伤的严重程度，并抑制几种生化参数（淀粉酶、脂肪酶、胰蛋白酶、胰蛋白酶原和髓过氧化物酶的活性以及促炎细胞因子的产生）。此外，TMMC通过抑制NF-kappa B和细胞外信号调节蛋白激酶1/2 （ERK1/2）的激活，抑制胰腺腺泡细胞死亡和肿瘤坏死因子(TNF)- α、白细胞介素(IL)-1 α和IL-6的产生。tnf - α、IL-1 α和IL-6的中和抗体可抑制分离胰腺腺泡细胞中cerulein诱导的细胞死亡。此外，药物阻断NF-kappa B/ERK1/2可减少分离胰腺腺泡细胞的死亡和tnf - α、IL-1 β和IL-6的产生。此外，TMMC处理后小鼠AP和肺损伤的严重程度降低。我们的研究结果表明，TMMC可以减少胰腺炎相关的并发症。
Kim T-H, Bae G-S, Oh H-J, Kim M-S, Park K-C, Koo BS, Kim B-J, Yang Y-S, Park D-E, Lee J-H, Seo S-W, Shin YK, Yun K-J, Sohn DH, Kim H-J, So H-S, Park R-K, Song H-J, Park S-J. 2',4',6'-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol 301: G694-G706, 2011. First published July 21, 2011; doi: 10.1152/ajpgi.00210.2010.-Acute pancreatitis (AP) is an inflammatory disease involving acinar cell injury and rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. 2',4',6'-Tris (methoxymethoxy) chalcone (TMMC), a synthetic chalcone derivative, displays potent anti-inflammatory effects. Therefore, we aimed to investigate whether TMMC might affect the severity of AP and pancreatitis-associated lung injury in mice. We used the cerulein hyperstimulation model of AP. Severity of pancreatitis was determined in cerulein-injected mice by histological analysis and neutrophil sequestration. The pretreatment of mice with TMMC reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (activity of amylase, lipase, trypsin, trypsinogen, and myeloperoxidase and production of proinflammatory cytokines). In addition, TMMC inhibited pancreatic acinar cell death and production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, and IL-6 by inhibiting NF-kappa B and extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation. Neutralizing antibodies for TNF-alpha, IL-1 alpha, and IL-6 inhibited cerulein-induced cell death in isolated pancreatic acinar cells. Moreover, pharmacological blockade of NF-kappa B/ERK1/2 reduced acinar cell death and production of TNF-alpha, IL-1 beta, and IL-6 in isolated pancreatic acinar cells. In addition, posttreatment of mice with TMMC showed reduced severity of AP and lung injury. Our results suggest that TMMC may reduce the complications associated with pancreatitis.