Hirano T, Manabe T, Steer M, Printz H, Calne R, Tobe T
Department of Surgery, Addenbrookes Hospital, Cambridge, England.
Surg Gynecol Obstet. 1993 Apr;176(4):371-81.
The current study was done to evaluate the effects of short term (60 minutes) pancreatic biliary duct obstruction (PBDO) with intraductal hypertension (IDH) stimulated by secretin (0.2 clinical unit per kilogram per hour) and caerulein (0.2 microgram per kilogram per hour) plus 30 minutes of temporary pancreatic ischemia (ISCH) produced by ligation of celiac and superior mesenteric artery on the exocrine pancreas and protective effects of a new potent protease inhibitor, ONO3307 in combination with xanthine oxidase inhibitor, allopurinol, in this multifactor related model of acute pancreatitis in rats. Twelve hours after PBDO with IDH plus ISCH, we observed hyperamylasemia (23 +/- 3 units per milliliter) (p < 0.01); moderate pancreatic histologic changes; pancreatic edema (water content--81 +/- 2 percent) (p < 0.02), as well as the impaired amylase (2,889 +/- 328 units per kilogram per hour) (p < 0.01) and cathepsin B output (7 +/- 3 units per kilogram per hour) (p < 0.01) into the pancreatic juice of rats stimulated by caerulein (control group--serum amylase levels, 6 +/- 1 units per milliliter; pancreatic water content, 74 +/- 1 percent. Furthermore, PBDO with IDH plus ISCH caused the redistribution of lysosomal enzyme from lysosomal fraction (12 kilo times gravity pellet; 40 +/- 3 percent; p < 0.01) to zymogen fraction (1.3 kilo times gravity pellet; 38 +/- 3 percent; p < 0.01) (control group--12 kilo times gravity pellet, 59 +/- 2 percent; 1.3 kilo times gravity pellet, 24 +/- 2 percent) and the impaired pancreatic adenylate energy metabolism (0.79 +/- 0.02, p < 0.02) (control group--energy charge equals 0.88 +/- 0.01). Only PBDO with IDH caused no significant changes. Although only ONO3307 or allopurinol therapy showed the partial significant protective effects against pancreatic injuries, improving serum amylase levels, the administration of ONO3307 in combination therapy with allopurinol showed almost complete protective effects against the pancreatic injuries induced by PBDO with IDH plus ISCH (serum amylase levels, 9 +/- 2 units per milliliter; pancreatic water content, 76 +/- 2 percent; amylase and cathepsin B output, 7,127 +/- 946 and 18 +/- 3 units per kilogram per hour; 1.3 kilo times gravity pellet, 28 +/- 2 percent; 12 kilo times gravity pellet, 54 +/- 2 percent, and energy charge equals 0.85 +/- 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)
本研究旨在评估在大鼠急性胰腺炎多因素相关模型中，由促胰液素（每千克每小时0.2临床单位）和蛙皮素（每千克每小时0.2微克）刺激产生的短期（60分钟）胰胆管梗阻（PBDO）及导管内高压（IDH），加上通过结扎腹腔干和肠系膜上动脉产生的30分钟暂时性胰腺缺血（ISCH）对外分泌胰腺的影响，以及新型强效蛋白酶抑制剂ONO3307与黄嘌呤氧化酶抑制剂别嘌呤醇联合使用的保护作用。在PBDO合并IDH加ISCH 12小时后，我们观察到高淀粉酶血症（23±3单位/毫升）（p<0.01）；中度胰腺组织学改变；胰腺水肿（含水量 - 81±2%）（p<0.02），以及蛙皮素刺激的大鼠胰液中淀粉酶（2889±328单位/千克每小时）（p<0.01）和组织蛋白酶B分泌量（7±3单位/千克每小时）（p<0.01）受损（对照组 - 血清淀粉酶水平，6±1单位/毫升；胰腺含水量，74±1%）。此外，PBDO合并IDH加ISCH导致溶酶体酶从溶酶体部分（12000倍重力沉淀；40±3%；p<0.01）重新分布到酶原部分（1300倍重力沉淀；38±3%；p<0.01）（对照组 - 12000倍重力沉淀，59±2%；1300倍重力沉淀，24±2%），以及胰腺腺苷酸能量代谢受损（0.79±0.02，p<0.02）（对照组 - 能荷等于0.88±0.01）。仅PBDO合并IDH未引起显著变化。虽然仅ONO3307或别嘌呤醇治疗对胰腺损伤显示出部分显著保护作用，改善了血清淀粉酶水平，但ONO3307与别嘌呤醇联合治疗对PBDO合并IDH加ISCH诱导的胰腺损伤显示出几乎完全的保护作用（血清淀粉酶水平，9±2单位/毫升；胰腺含水量，76±2%；淀粉酶和组织蛋白酶B分泌量，7127±946和18±3单位/千克每小时；1300倍重力沉淀，28±2%；12000倍重力沉淀，54±2%，能荷等于0.85±0.02）。（摘要截断于400字）
