Schneider J, Friderichs E, Heintze K, Flohé L
Grünenthal GmbH, Center of Research, Aachen, West Germany.
Circ Shock. 1990 Feb;30(2):97-106.
A 4 hr intravenous infusion of Escherichia coli endotoxin in a total dose of 100 mg/kg produced significant morphological and functional pulmonary alterations in pentobarbitone anesthetized rats. Lung vascular permeability index was increased from 2.11 +/- 0.34 in normal rats to 4.82 +/- 0.65 in untreated endotoxemic rats. Treatment of endotoxemic rats with recombinant human superoxide dismutase (r-HSOD) in doses of 0.1, 0.215, and 0.464 mg/kg.min i.v., infused concomitantly with endotoxin, dose-dependently reduced the permeability index to 3.28 +/- 0.96, 2.83 +/- 0.55 (P less than 0.05), and 2.16 +/- 0.65 (P less than 0.05). The wet lung weight was 523 +/- 15 and 664 +/- 46 mg/100 g bwt in normal and in untreated endotoxemic rats, respectively. r-HSOD dose-dependently inhibited the endotoxin-induced increase in wet lung weight to 617 +/- 40, 577 +/- 31, and 559 +/- 39 (P less than 0.05) mg/100 g bwt. r-HSOD (0.464 mg/kg.min) did not affect permeability index and wet lung weight in normal, nonintoxicated rats. Endotoxin infusion produced a significant increase in respiratory rate (max. +69%) and blood gas alterations, indicating a hyperventilatory hypocapnia in endotoxemic control rats. Infusion of r-HSOD (0.464 mg/kg.min) significantly inhibited the endotoxin-induced tachypnoe (max. +13%) and blunted the alterations in arterial hydrogen carbonate content and carbon dioxide tension. In conclusion, infusion of r-HSOD dose-dependently and significantly inhibited pulmonary edema formation and hyperventilatory dyspnoe in endotoxemic rats.
以100mg/kg的总剂量对戊巴比妥麻醉的大鼠进行4小时的大肠杆菌内毒素静脉输注，可导致其肺部出现显著的形态学和功能改变。肺血管通透性指数从正常大鼠的2.11±0.34增加到未治疗的内毒素血症大鼠的4.82±0.65。以内毒素输注同时静脉注射0.1、0.215和0.464mg/kg·min剂量的重组人超氧化物歧化酶（r-HSOD）治疗内毒素血症大鼠，可使通透性指数剂量依赖性降低至3.28±0.96、2.83±0.55（P<0.05）和2.16±0.65（P<0.05）。正常大鼠和未治疗的内毒素血症大鼠的湿肺重量分别为523±15和664±46mg/100g体重。r-HSOD剂量依赖性地抑制内毒素诱导的湿肺重量增加，分别降至617±40、577±31和559±39（P<0.05）mg/100g体重。r-HSOD（0.464mg/kg·min）对正常、未中毒大鼠的通透性指数和湿肺重量无影响。内毒素输注使呼吸频率显著增加（最大增加69%）并导致血气改变，表明内毒素血症对照大鼠出现通气过度性低碳酸血症。输注r-HSOD（0.464mg/kg·min）可显著抑制内毒素诱导的呼吸急促（最大增加13%），并减轻动脉碳酸氢盐含量和二氧化碳张力的改变。总之，输注r-HSOD可剂量依赖性且显著地抑制内毒素血症大鼠的肺水肿形成和通气过度性呼吸困难。
