Wisner J, Green D, Ferrell L, Renner I
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Gut. 1988 Nov;29(11):1516-23. doi: 10.1136/gut.29.11.1516.
The effects of a polyethylene glycol linked oxygen free radical scavenger enzyme, superoxide dismutase (PEG:SOD) on caerulein induced acute pancreatitis (AP) in rats were examined. Pancreas weights and serum amylase concentrations in rats given a three hour continuous intravenous infusion of caerulein (7.5 micrograms/kg/h, n = 18) for induction of AP followed by a three hour infusion of normal saline were significantly raised by approximately 25% (p less than 0.005) and 750% (p less than 0.001), respectively, compared with values obtained in control rats (n = 7) infused for six hours with normal saline alone. A single intraperitoneal injection of either 1 X 10(4) U/kg (n = 6), 2 X 10(4) U/kg (n = 5), or 4 X 10(4) U/kg (n = 5) of PEG:SOD immediately before caerulein infusion did not significantly alter pancreas weights, serum amylase content, or pancreatic histopathology compared with rats given caerulein alone. By contrast, a single intravenous bolus injection of 4 X 10(4) U/kg (n = 9) of PEG:SOD before caerulein treatment significantly reduced serum amylase content by approximately 25% (p less than 0.05) and a continuous six hour intravenous infusion of 4 X 10(4) U/kg/h of PEG:SOD (n = 5) produced significant reductions of approximately 25% (p less than 0.001), 35% (p less than 0.05), and 50% (p less than 0.01) in pancreas weights, serum amylase concentrations, and acinar cell vacuolisation (p less than 0.01), respectively, compared with values in rats given caerulein alone. In studies using bovine serum albumin linked to polyethylene glycol and infused for six hours at protein concentrations identical to high dose PEG:SOD (n = 6), no beneficial effects against caerulein induced AP were observed. These data suggest that (a) oxygen derived free radicals are involved in the early pathogenesis of caerulein induced AP in rats, and (b) the greatly extended circulating half life of polyethylene PEG:SOD ( > 35 hours in rats compared with less than six minutes for native superoxide dismutase) may make this compound more suitable than native superoxide dismutase as a potential therapeutic agent in AP.
研究了一种聚乙二醇连接的氧自由基清除酶——超氧化物歧化酶（PEG:SOD）对大鼠蛙皮素诱导的急性胰腺炎（AP）的影响。通过持续3小时静脉输注蛙皮素（7.5微克/千克/小时，n = 18）诱导大鼠发生AP，随后输注3小时生理盐水，与仅输注6小时生理盐水的对照大鼠（n = 7）相比，诱导AP大鼠的胰腺重量和血清淀粉酶浓度显著升高，分别约升高25%（p < 0.005）和750%（p < 0.001）。在蛙皮素输注前立即腹腔注射1×10⁴单位/千克（n = 6）、2×10⁴单位/千克（n = 5）或4×10⁴单位/千克（n = 5）的PEG:SOD，与仅给予蛙皮素的大鼠相比，胰腺重量、血清淀粉酶含量或胰腺组织病理学无显著变化。相比之下，在蛙皮素治疗前静脉推注4×10⁴单位/千克（n = 9）的PEG:SOD可使血清淀粉酶含量显著降低约25%（p < 0.05），持续6小时静脉输注4×10⁴单位/千克/小时的PEG:SOD（n = 5）可使胰腺重量、血清淀粉酶浓度和腺泡细胞空泡化分别显著降低约25%（p < 0.001）、35%（p < 0.05）和50%（p < 0.01），与仅给予蛙皮素的大鼠相比。在使用与聚乙二醇连接的牛血清白蛋白并以与高剂量PEG:SOD相同的蛋白质浓度输注6小时的研究中（n = 6），未观察到对蛙皮素诱导的AP有有益作用。这些数据表明：（a）氧衍生的自由基参与大鼠蛙皮素诱导的AP的早期发病机制；（b）聚乙二醇PEG:SOD大大延长的循环半衰期（大鼠中> 35小时，而天然超氧化物歧化酶小于6分钟）可能使该化合物比天然超氧化物歧化酶更适合作为AP的潜在治疗药物。
