DDC递增法诱导大鼠胰腺纤维化动物模型的研究

目的建立DDC剂量递增腹腔内注射诱发大鼠胰腺纤维化动物模型方法,并与常规恒量DDC腹腔内注射方法比较。方法70只Wistar大鼠随机分为4组:生理盐水注射组、低剂量DDC恒量注射组(600 mg/kg/次。每周2次,共8次)、高剂量DDC恒量注射组(1 000 mg/kg/次,每周2次,共8 次)及DDC剂量递增注射组(首次400 mg/kg/次,以10%浓度连续递增,每周2次,共8次)。每周于注射后2d h、48 h、1周、2周、3周、4周6个时间点分别随机处死3只大鼠,并对胰、肝、肾组织进行病理学诊断与胶原纤维测定。实验中观察动物并发症(鼻出血,尿失禁,震颤)的发生率及死亡率。结果DDC递增组大鼠并发症较少,但成模时间及纤维化程度与恒量注射组无显著性差异,纤维化程度增加过程较为渐进,提示更为接近胰腺纤维化的发展过程。结论DDC注射递增法可以建立大鼠胰腺纤维化动物模型, 此模型较常规恒定DDC腹腔注射法更为优越。

Progressively increasing dosage of DDC induced pancreatic fibrosis in rats

Objective To explore the possibility and advantage of the rat pancreatic fibrosis model induced by repeated intraperitoneal injection of progressively increasing dosage of diethyldithiocarbamate (DDC), a superoxide dismutase (SOD) inhibitor. Methods 70 Wistar rats were randomly divided into four groups. Rats in group 1 received intraperitoneal injections of 600 mg/ kg DDC twice a week; group 2 received 1 000mg/kg DDC twice a week; group 3 were given progressively increasing dosage of DDC, with an initial dose of 400 mg/kg DDC followed by an 10% increase each time; and group 4 received intraperitoneal injections of 10 ml/kg of saline twice a week. The rats in each group were killed at 24, 48 hours and 1, 2, 3, 4 weeks after DDC administration. Responses of the animals in each group to DDC were observed, and the pancreas, liver and kidney specimens from each killed rat were stained with hematoxylin eosin and with Masson's trichrome. Results Group 3 had fewer complications than group 1 and 2. There was no significant difference in the time required to establish the pancreatic fibrosis model between all DDC groups. Conclusions Repeated intrapertoneal injection of progressively increasing dosage of DDC is a new experimental method to develop a pancreatic fibrosis model.