Gukovsky Ilya, Reyes Christopher N, Vaquero Eva C, Gukovskaya Anna S, Pandol Stephen J
Research Center for Alcoholic Liver and Pancreatic Diseases and Department of Medicine, University of California, Los Angeles and Veterans Affairs Greater Los Angeles Healthcare System, 90073, USA.
Am J Physiol Gastrointest Liver Physiol. 2003 Jan;284(1):G85-95. doi: 10.1152/ajpgi.00138.2002.
Treatments for pancreatitis are limited. Activation of transcription factor NF-kappaB, a key regulator of inflammatory molecule expression, is an early event in experimental pancreatitis and correlates with the inflammatory response. We report here that curcumin, a natural phytochemical known to inhibit NF-kappaB and activator protein (AP)-1, another important proinflammatory transcription factor, ameliorates pancreatitis in two rat models. In both cerulein pancreatitis and pancreatitis induced by a combination of ethanol diet and low-dose CCK, curcumin improved the severity of the disease as measured by a number of parameters (histology, serum amylase, pancreatic trypsin, and neutrophil infiltration). Curcumin markedly inhibited NF-kappaB and AP-1 activation, assessed by DNA binding and degradation of inhibitory IkappaB proteins, and the induction of mRNAs for cytokines IL-6 and TNF-alpha, the chemokine KC, and inducible nitric oxide synthase in pancreas. Curcumin also blocked CCK-induced NF-kappaB and AP-1 activation in isolated pancreatic acini. Our findings indicate that blocking key signals of the inflammatory response ameliorates pancreatitis in both ethanol and nonethanol models. They suggest that curcumin, which is currently in clinical trials for cancer prevention, may be useful for treatment of pancreatitis.
胰腺炎的治疗方法有限。转录因子NF-κB是炎症分子表达的关键调节因子，其激活是实验性胰腺炎的早期事件，并与炎症反应相关。我们在此报告，姜黄素是一种已知可抑制NF-κB和另一种重要的促炎转录因子激活蛋白（AP）-1的天然植物化学物质，可改善两种大鼠模型中的胰腺炎。在雨蛙肽诱导的胰腺炎以及由乙醇饮食和低剂量胆囊收缩素联合诱导的胰腺炎中，姜黄素通过多个参数（组织学、血清淀粉酶、胰腺胰蛋白酶和中性粒细胞浸润）测量改善了疾病的严重程度。通过DNA结合和抑制性IkappaB蛋白的降解评估，姜黄素显著抑制了NF-κB和AP-1的激活，以及胰腺中细胞因子IL-6和TNF-α、趋化因子KC和诱导型一氧化氮合酶mRNA的诱导。姜黄素还阻断了分离的胰腺腺泡中胆囊收缩素诱导的NF-κB和AP-1激活。我们的研究结果表明，阻断炎症反应的关键信号可改善乙醇和非乙醇模型中的胰腺炎。这些结果提示，目前正在进行癌症预防临床试验的姜黄素可能对胰腺炎的治疗有用。
