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Wistar大鼠急性胰腺炎实验模型:糖皮质激素治疗概况

Experimental model of acute pancreatitis in Wistar rat: glucocorticoid treatment profile.

作者信息

Cosen-Binker Laura Iris, Binker Marcelo Gustavo, Negri Gustavo, Tiscornia Osvaldo

机构信息

Programa de Estudios Pancreáticos, Hospital de Clínicas, Universidad de Buenos Aires, Argentina.

出版信息

Dig Dis Sci. 2003 Aug;48(8):1453-64. doi: 10.1023/a:1024791101859.

DOI:10.1023/a:1024791101859
PMID:12924636
Abstract

Severe acute pancreatitis may be triggered by an extrapancreatic insult at the peri-Vaterian duodenum such as that occurring in the short-term, 20 min closed duodenal loop model in Wistar rat, which mimics biliary acute pancreatitis or that following endoscopy. Glucocorticoids are immunological modulators whose therapeutic value is worth investigating. Wistar male rats were used under standardized conditions. Acute pancreatitis was induced by instillation of a 7% sodium tauraocholate solution with 5 drops of methylene blue to monitor absence of duodenal bilio pancreatic reflux into the peri-Vaterian duodenum for 20 min. Detection of biliopancreatic reflux with methylene blue was an exclusion criterion. Different doses and times of administration of subcutaneous hydrocortisone were evaluated. Biochemical assays were carried out in blood samples and pancreatic and lung tissue, while histpathological studies were done in the pancreas, lung liver, duodenum, spleen, kidneys, suprarenal glands, and stomach. Animals subjected to the experimental model developed severe acute pancreatitis. According to the dose and time of administration, hydrocortisone therapy was effective and beneficial at a dose of 4 mg/kg give 30 min before inducing acute pancreatitis. It was ineffective when doses were <4 mg/kg and given before sodium taurocholate harmful when the dose was >4 mg/kg and given either before or after. Thus, the proposed model is valid and useful to study the initiation mechanism of acute pancreatitis caused extrapancreatically while its amelioration by glucocorticoid is related the dose and time factor to achieve therapeutical results.

摘要

重症急性胰腺炎可能由胰周十二指肠的胰腺外损伤引发,比如在Wistar大鼠短期(20分钟)闭合十二指肠环模型中出现的损伤,该模型模拟了胆源性急性胰腺炎或内镜检查后的情况。糖皮质激素是免疫调节剂,其治疗价值值得研究。在标准化条件下使用Wistar雄性大鼠。通过向胰周十二指肠内滴注7%牛磺胆酸钠溶液并加入5滴亚甲蓝来诱导急性胰腺炎,持续20分钟,以监测十二指肠胆胰反流情况,亚甲蓝检测胆胰反流是一项排除标准。评估了皮下注射氢化可的松的不同剂量和给药时间。对血液样本以及胰腺和肺组织进行生化检测,同时对胰腺、肺、肝、十二指肠、脾、肾、肾上腺和胃进行组织病理学研究。接受实验模型的动物发生了重症急性胰腺炎。根据给药剂量和时间,在诱导急性胰腺炎前30分钟给予4mg/kg剂量的氢化可的松治疗有效且有益。当剂量<4mg/kg且在牛磺胆酸钠之前给药时无效,当剂量>4mg/kg且在牛磺胆酸钠之前或之后给药时有害。因此,所提出的模型对于研究胰腺外源性急性胰腺炎的起始机制是有效且有用的,而糖皮质激素对其的改善作用与实现治疗效果的剂量和时间因素有关。

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