二丁基二氯化物尾静脉注射建立大鼠慢性胰腺炎模型

Experimental chronic pancreatitis induced by dibutyltin dichloride.

目的 探讨经尾静脉注射二丁基二氯化物建立大鼠慢性胰腺炎模型的方法，为慢性胰腺炎纤维化机制研究提供一种合适的动物模型。方法 将SD大鼠随机分为实验组和对照组，每组再分为1，7，14，21，28，60d6个观察点，每个时间点各5只大鼠。实验组大鼠尾静脉注射二丁基二氯化物8mg／kg体重，对照组注射相同剂量的乙醇和甘油溶剂。上述时间点分别处死大鼠，收集血液和胰腺标本。检测血清淀粉酶、脂肪酶、透明质酸浓度。观察胰腺形态，病理改变，胶原染色评价纤维化程度。结果 造模后1d胰腺组织水肿，表现为急性中度间质性水肿性胰腺炎；7d炎症加重，表现为腺泡肿胀，散在的腺泡细胞坏死；14d广泛的炎症细胞浸润，伴轻度纤维化；21～28d胶原沉积，纤维化加重，可见大量的纤维结缔组织；60d，胰腺小叶结构破坏，腺泡消失，广泛间质纤维化。结论 尾静脉注射二丁基二氯化物是一种简便、有效的大鼠慢性胰腺炎模型制作方法，能为慢性胰腺炎纤维化的研究提供合适的动物模型。

Objective To present a new pancreatitis model in rats suitable for investigation of the processes and mechanisms leading to pancreatic fibrosis. The model was established by tail vein injection of dibutyltin dichloride （DBTC）. Methods Spraque-Dawley rats were induced by intravenous application of 8 mg/kg body wt DBTC. Animals were killed at 1, 7, 14, 21, 28, 60 days. Pancreatitis was characterized by microscopy, histology and Van Gieson staining. Blood was obtained by portal vein puncture, s-amylase activity, lipase activity and hyaluronic acid concentration were assayed. Results DBTC induced an acute edematous pancreatitis within 1 day. The aeini dilated and scattered acinar cell necrosis was found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 21 to 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was characterized by an extended interstitial fibrosis at the end of 2 months. Conclusions DBTC-induced pancreatitis in rats is a handy and effective experimental method. The model is suitable to study development of pancreatic fibrosis in chronic pancreatitis.