Effect of IS-741 on ethionine-induced acute pancreatitis in rats: relation to pancreatic acinar cell regeneration
Effect of IS-741 on ethionine-induced acute pancreatitis in rats: relation to pancreatic acinar cell regeneration
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IS-741 对乙硫氨酸诱导的大鼠急性胰腺炎的影响：与胰腺腺泡细胞再生的关系
DOI：
10.1007/s005350300045
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发表时间：
2003
影响因子：
6.3
通讯作者：
K. Mitamura
中科院分区：
文献类型：
--
作者：
T. Imamura;J. Niikawa;K. Kitamura;Akira Takahashi;A. Ikegami;Hitoshi Yoshida;Shigeki Tanaka;K. Mitamura
研究背景IS-741可抑制急性胰腺炎时中性粒细胞浸润胰腺及其他器官引起的组织破坏。方法：低蛋白饲料喂养大鼠11 d，最后4 d每天腹腔注射DL-乙醇（20 mg/100 g），观察IS-741对DL-乙醇诱导的大鼠急性胰腺炎的影响。为了评估对乙硫氨酸诱导的胰腺炎的治疗效果，将IS-741（10 mg/kg s.c.）从第二次注射乙撑双胍后开始，每8小时给药一次（IS组）。对照大鼠使用等体积的生理盐水作为IS-741（对照组）的替代品。分别于末次注射乙醇后1、3、5和7天处死大鼠。收集血液以测量炎性细胞因子白细胞介素-8的浓度。对胰腺进行组织学和生化检查。测定胰腺重量、DNA含量和蛋白质水平。结果：对照组胰腺组织在末次注射乙醇后1d（第1天）可见明显的炎性细胞浸润，腺泡细胞广泛坏死。IS-741治疗组大鼠急性胰腺炎严重程度减轻。第1天，IS组胰腺湿重和DNA含量高于对照组。在第7天，IS组的每DNA胰腺蛋白水平高于对照组。结论：IS-741可减轻乙硫氨酸诱导的大鼠急性胰腺炎，IS-741可作为治疗重症急性胰腺炎的有效药物。
BackgroundTissue destruction arising from neutrophil infiltration of the pancreas and other organs in acute pancreatitis is supposed to be suppressed by IS-741. We studied the effect of IS-741 on acute pancreatitis induced by DL-ethionine in rats.Methods:Rats fed with a low protein diet for 11 days received daily intraperitoneal administration of DL-ethionine (20 mg/100 g) for the last 4 days of the diet. To evaluate the therapeutic effect on ethionine-induced pancreatitis, IS-741 (10 mg/kg s.c.) was administered every 8 h beginning after the second ethionine injection (IS group). An equal volume of saline was used for control rats as alternative to IS-741 (control group). The rats were killed 1, 3, 5, and 7 days after the last injection of ethionine. Blood was collected to measure concentrations of the inflammatory cytokine, interleukin-8. Histologic and biochemical examinations of the pancreas were performed. The pancreatic weight, DNA content, and protein levels were determined. The pancreas was histologically examined.Results:Pancreatic tissue in the control group showed marked infiltration of inflammatory cells, and acinar cell necrosis was widespread 1 day after the last injection of ethionine (day 1). The severity of acute pancreatitis was alleviated in rats treated with IS-741 (IS group). Pancreatic wet weight and DNA content in the IS group were higher than those in the control group on day 1. Pancreatic protein level per DNA in the IS group was higher than that in the control group on day 7. The plasma interleukin-8 level in the control group was higher than that in the IS group on day 5.Conclusions:Therapeutic administration of IS-741 ameliorated ethionine-induced acute pancreatitis in rats, and IS-741 could be a useful drug to treat patients with severe acute pancreatitis.