Puig-Diví V, Molero X, Salas A, Guarner F, Guarner L, Malagelada J R
Digestive Research Unit, Hospital General Vall d'Hebron, Barcelona, Spain.
Pancreas. 1996 Nov;13(4):417-24. doi: 10.1097/00006676-199611000-00012.
Despite being a common disease in humans, little is known about the etiopathogenesis of and effective therapeutic approaches to chronic pancreatitis, due mainly to the fact that few simple animal models suitable to study inflammatory and fibrogenetic processes have been described in the pancreas. Trinitrobenzene sulfonic acid (TNBS) induces chronic colitis and cholangitis in the rat. We hypothesized that TNBS instillation into the pancreatic ducts could also result in the development of a chronic pancreatic disease. The biliopancreatic duct of rats was cannulated and tied close to the liver. TNBS [0.4 ml of 2% TNBS in phosphate-buffered saline (PBS)-10% ethanol, pH 8] was infused into the pancreas under a continuous controlled-pressure system. Control rats underwent the same procedure using vehicle only. Pathology assessment of TNBS-treated rats examined at 48 h was consistent with severe acute necrotizing pancreatitis, having a morality rate of 31% and serum amylase activity of 37.4 +/- 8.8 U/ml at 24 h and 13.3 +/- 1.7 U/ml at 48 h (p < 0.01 for both time points compared to PBS/ethanol-treated rats). Groups of 10 rats each were killed at 3, 4, and 6 week after the surgical procedure. Morphological examination revealed changes mimicking features of chronic pancreatitis in humans in 80% (32 of 40) of TNBS-treated rats, consisting in various degrees of periductal and lobular fibrosis, duct stenosis, patchy acute and chronic inflammatory cell infiltrates, and signs of gland atrophy. Animals developing chronic disease had a weight gain rate significantly lower than that of control rats. Serum amylase, fasting glucose, and a glucose tolerance test were not different in diseased or control rats. In conclusion, we were able to induce chronic fibrogenetic inflammatory disease in the pancreas after a single pulse instillation of TNBS into the pancreatic ducts. This might be a useful animal model to study the pathophysiology of inflammatory, fibrogenetic, and reparative processes in pancreatic tissue.
尽管慢性胰腺炎在人类中是一种常见疾病，但由于胰腺中适合研究炎症和纤维化过程的简单动物模型很少，因此对其发病机制和有效治疗方法了解甚少。三硝基苯磺酸（TNBS）可诱发大鼠慢性结肠炎和胆管炎。我们推测，将TNBS注入胰管也可能导致慢性胰腺疾病的发生。将大鼠的胆胰管插管并在靠近肝脏处结扎。在连续控压系统下，将TNBS[0.4ml 2%TNBS溶于磷酸盐缓冲盐水（PBS）-10%乙醇，pH 8]注入胰腺。对照大鼠仅接受相同的溶剂处理。对48小时时接受TNBS处理的大鼠进行病理学评估，结果与严重急性坏死性胰腺炎一致，死亡率为31%，24小时时血清淀粉酶活性为37.4±8.8 U/ml，48小时时为13.3±1.7 U/ml（与PBS/乙醇处理组大鼠相比，两个时间点均p<0.01）。在手术后3、4和6周，每组10只大鼠被处死。形态学检查显示，80%（40只中的32只）接受TNBS处理的大鼠出现了类似人类慢性胰腺炎特征的变化，包括不同程度的导管周围和小叶纤维化、导管狭窄、散在的急性和慢性炎症细胞浸润以及腺体萎缩迹象。发生慢性疾病的动物体重增加率明显低于对照大鼠。患病大鼠和对照大鼠的血清淀粉酶、空腹血糖和葡萄糖耐量试验无差异。总之，我们通过向胰管单次脉冲注入TNBS，成功诱导了胰腺慢性纤维化炎症性疾病。这可能是一种用于研究胰腺组织中炎症、纤维化和修复过程病理生理学的有用动物模型。
