Imamura Tsunao, Niikawa Junichi, Kitamura Katsuya, Takahashi Akira, Ikegami Akitoshi, Yoshida Hitoshi, Tanaka Shigeki, Mitamura Keiji
Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
J Gastroenterol. 2003;38(3):260-7. doi: 10.1007/s005350300045.
Tissue 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.
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.
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.
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.
急性胰腺炎时，胰腺及其他器官因中性粒细胞浸润而导致的组织破坏被认为可被IS - 741抑制。我们研究了IS - 741对DL - 乙硫氨酸诱导的大鼠急性胰腺炎的影响。
用低蛋白饮食喂养大鼠11天，在饮食的最后4天，每天腹腔注射DL - 乙硫氨酸（20 mg/100 g）。为评估对乙硫氨酸诱导的胰腺炎的治疗效果，在第二次注射乙硫氨酸后开始，每8小时皮下注射IS - 741（10 mg/kg）（IS组）。用等体积的生理盐水替代IS - 741用于对照大鼠（对照组）。在最后一次注射乙硫氨酸后的1、3、5和7天处死大鼠。采集血液以测量炎症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。对胰腺进行组织学检查。
对照组胰腺组织在最后一次注射乙硫氨酸后1天（第1天）显示出明显的炎症细胞浸润，腺泡细胞坏死广泛存在。IS - 741治疗的大鼠（IS组）急性胰腺炎的严重程度有所减轻。在第1天，IS组的胰腺湿重和DNA含量高于对照组。在第7天，IS组每DNA的胰腺蛋白质水平高于对照组。在第5天，对照组的血浆白细胞介素 - 8水平高于IS组。
IS - 741的治疗性给药改善了乙硫氨酸诱导的大鼠急性胰腺炎，IS - 741可能是治疗重症急性胰腺炎患者的一种有用药物。
