A new thrapy for severe acute pancreatitis by regulating the cannabinoid

大麻素是大麻的基本药理成分。Anandamide （ANA）是一种大麻素，近年来已经明确Anandamide是脓毒性休克的介质之一。急性胰腺炎的发病机制尚不清楚，急性胰腺炎与大麻素之间是否存在关系尚不清楚。因此，我们旨在澄清急性胰腺炎与大麻素的关系，并寻找一种新的治疗方法来调节大麻素在急性胰腺炎中的作用。采用静脉注射小鼠脑蓝蛋白诱导轻度水肿性胰腺炎，胆胰管注射5%牛牛胆酸钠诱导重度坏死性胰腺炎。胰腺炎诱导后采血，采用LC/MS/MS法测定血浆anandamide值。对肾脏进行免疫组织化学染色以评估大麻素受体1 （CBI受体）的外观。最后，在诱导急性重症胰腺炎后给大鼠注射CB1受体拮抗剂（SR141716A），明确大麻素在急性胰腺炎发病机制中的作用。急性胰腺炎诱导后，anandamide的数值升高，重症胰腺炎的数值明显高于轻度胰腺炎。只有在诱发严重急性胰腺炎后，肾小球中CBI受体的出现才会升高。无论注射SR141716A，胰腺局部炎症变化无明显差异。然而，注射SRI41716A后，死亡率明显降低。这些发现表明大麻素在急性胰腺炎的恶化中起着重要的作用，大麻素的调节可能是治疗重症急性胰腺炎的新方法。

Cannabinoids are the pharmacologically essential components of marihuana. Anandamide (ANA) is one of the cannabinoids and it has recently become clear that anandamide is one of the mediators in septic shock. The pathogenesis of acute pancreatitis is not clearly understood and whether there is a relationship between acute pancreatitis and cannabinoids is unknown. Therefore, we aimed to clarify the relationship between acute pancreatitis and cannabinoids and to find a new therapy to regulate the cannabinoids in acute pancreatitis. Rats were injected with cerulein intravenously to induce mild edematous pancreatitis and were injected with 5% sodium taurochorate to the bilio-pancreatic duct to induce severe necrotizing pancreatitis. After the induction of pancreatitis, blood was collected to measure the plasma anandamide value by the LC/MS/MS method. Kidneys were stained immunohistochemically to evaluate the appearance of the cannabinoid receptor 1 (CBI receptor). Finally, rats were injected with the antagonist of the CB1 receptor (SR141716A) after the induction of severe acute pancreatitis to clarify the role of cannabinoids in the pathogenesis of acute pancreatitis. After the induction of acute pancreatitis, the values of the anandamide increased and the value of severe pancreatitis was significantly higher than that of mild pancreatitis. The appearance of CBI rceptors in the glomerulus of the kidney was elevatd only after the induction of severe acute pancreatitis. The local inflammatory changes in the pancreas were not different regardless of the injection of SR141716A. However, the mortality rate was significantly reduce by the injection of SRI41716A. These findings indicate that cannabinoids have an important roll in the deterioration of acute pancreatitis and that the regulation of cannabinoids could be a new therapy for severe acute pancreatitis.