Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Shock. 2012 May;37(5):478-84. doi: 10.1097/SHK.0b013e31824653be.
Severe acute pancreatitis remains a life-threatening disease with a high mortality rate among a defined proportion of those affected. Apoptosis has been hypothesized to be a beneficial form of cell death in acute pancreatitis. Honokiol, a low-molecular-weight natural product, possesses the ability of anti-inflammation and apoptosis induction. Here, we investigate whether honokiol can ameliorate severe acute pancreatitis and the associated acute lung injury in a mouse model. Mice received six injections of cerulein at 1-h intervals, then given one intraperitoneal injection of bacterial lipopolysaccharide for the induction of severe acute pancreatitis. Moreover, mice were intraperitoneally given vehicle or honokiol 10 min after the first cerulein injection. Honokiol protected against the severity of acute pancreatitis in terms of increased serum amylase and lipase levels, pancreas pathological injury, and associated acute lung injury. Honokiol significantly reduced the increases in serum tumor necrosis factor-α, interleukin 1, and nitric oxide levels 3 h and serum high-mobility group box 1 24 h after acute pancreatitis induction. Honokiol also significantly decreased myeloperoxidase activities in the pancreas and the lungs. Endoplasmic reticulum stress-related molecules eIF2α (phosphorylated) and CHOP protein expressions, apoptosis, and caspase-3 activity were increased in the pancreas of mice with severe acute pancreatitis, which was unexpectedly enhanced by honokiol treatment. These results suggest that honokiol protects against acute pancreatitis and limits the spread of inflammatory damage to the lung in a severe acute pancreatitis mouse model. The acceleration of pancreatic cell apoptosis by honokiol may play a pivotal role.
严重的急性胰腺炎仍然是一种危及生命的疾病，在一定比例的患者中死亡率很高。细胞凋亡被认为是急性胰腺炎中一种有益的细胞死亡形式。和厚朴酚是一种低分子量天然产物，具有抗炎和诱导细胞凋亡的能力。在这里，我们研究了和厚朴酚是否可以改善小鼠模型中的严重急性胰腺炎和相关的急性肺损伤。小鼠每隔 1 小时接受 6 次胆囊收缩素注射，然后腹腔内注射细菌脂多糖诱导严重急性胰腺炎。此外，在第一次注射胆囊收缩素后 10 分钟，小鼠腹腔内给予载体或和厚朴酚。和厚朴酚可防止急性胰腺炎的严重程度，表现为血清淀粉酶和脂肪酶水平升高、胰腺病理损伤和相关的急性肺损伤。和厚朴酚可显著降低急性胰腺炎诱导后 3 小时血清肿瘤坏死因子-α、白细胞介素 1 和一氧化氮水平以及 24 小时血清高迁移率族蛋白 1 水平的升高。和厚朴酚还显著降低了胰腺和肺中的髓过氧化物酶活性。内质网应激相关分子 eIF2α（磷酸化）和 CHOP 蛋白表达、细胞凋亡和 caspase-3 活性在严重急性胰腺炎小鼠的胰腺中增加，而和厚朴酚处理意外地增强了这些增加。这些结果表明，和厚朴酚可防止急性胰腺炎，并在严重急性胰腺炎小鼠模型中限制炎症损伤向肺部的扩散。和厚朴酚加速胰腺细胞凋亡可能发挥关键作用。
