Chen Y Z, Ikei S, Yamaguchi Y, Sameshima H, Sugita H, Moriyasu M, Ogawa M
Department of Surgery II, Kumamoto University Medical School, Japan.
J Int Med Res. 1996 Jan-Feb;24(1):59-68. doi: 10.1177/030006059602400108.
The effects of pancreatic secretory trypsin inhibitor (PSTI) on cerulein-induced pancreatitis were studied in a rat model. Arg44 of PSTI was replaced by Ser using site-directed mutagenesis (R44S-PSTI). R44S-PSTI has a longer half-life than the natural form. Pancreatitis was induced by four intramuscular injections of cerulein (50 microgram/kg at 1 h intervals). Continuous intravenous infusion of R44S-PSTI began at a dose of 20 micrograms/kg/h 30 min before the first cerulein injection, and was completed 3 h after the last cerulein injection. Tumour necrosis factor (TNF-alpha) production by isolated peritoneal macrophages from rats with cerulein-induced pancreatitis increased following lipopolysaccharide stimulation, compared to control rats (P < 0.01). R44S-PSTI administration significantly decreased the TNF-alpha production by peritoneal macrophages from rats with cerulein-induced pancreatitis (P < 0.05). In addition, R44S-PSTI significantly reduced serum amylase activity (P < 0.01) and pancreatic wet weight after pancreatitis induction (P < 0.05). Histological examination revealed marked acinar cell vacuolization, interstitial oedema, and cellular infiltration in cerulein-induced pancreatitis, but a lesser degree of histological change in rats that were treated with R44S-PSTI. Prophylactic use of intravenous R44S-PSTI infusion may reduce the severity of acute pancreatitis either histologically or serologically.
在大鼠模型中研究了胰腺分泌型胰蛋白酶抑制剂（PSTI）对雨蛙肽诱导的胰腺炎的影响。使用定点诱变将PSTI的Arg44替换为Ser（R44S-PSTI）。R44S-PSTI的半衰期比天然形式更长。通过四次肌肉注射雨蛙肽（50微克/千克，间隔1小时）诱导胰腺炎。在第一次注射雨蛙肽前30分钟开始以20微克/千克/小时的剂量持续静脉输注R44S-PSTI，并在最后一次注射雨蛙肽后3小时结束。与对照大鼠相比，雨蛙肽诱导的胰腺炎大鼠分离的腹腔巨噬细胞在脂多糖刺激后肿瘤坏死因子（TNF-α）产生增加（P<0.01）。给予R44S-PSTI可显著降低雨蛙肽诱导的胰腺炎大鼠腹腔巨噬细胞的TNF-α产生（P<0.05）。此外，R44S-PSTI显著降低血清淀粉酶活性（P<0.01）以及胰腺炎诱导后的胰腺湿重（P<0.05）。组织学检查显示，雨蛙肽诱导的胰腺炎有明显的腺泡细胞空泡化、间质水肿和细胞浸润，但接受R44S-PSTI治疗的大鼠组织学变化程度较轻。预防性静脉输注R44S-PSTI可能在组织学或血清学方面减轻急性胰腺炎的严重程度。
