Taylor J L, Carraway M S, Piantadosi C A
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Physiol. 1998 Apr;274(4):L582-90. doi: 10.1152/ajplung.1998.274.4.L582.
Heme oxygenase (HO)-1, which catalyzes heme breakdown, is induced by oxidative stress and may protect against oxidative injury. We hypothesized that induction of HO-1 by hemoglobin (Hb) in the lung would protect the rat from pulmonary O2 toxicity. Rats given intratracheal (i.t.) Hb showed lung-specific induction of HO-1 by 8 h by Western analysis. Rats were then pretreated for 8 h before 60 h of exposure to 100% O2 with either IT normal saline, HB, or Hb plus the HO-1 inhibitor tinprotoporphyrin (SnPP). Both the Hb + O2 and Hb + O2 + SnPP animals had less lung injury than normal saline controls as indicated by lower pleural fluid volumes and wet-to-dry weight ratios (P < 0.01). The improvement in injury in the two Hb-treated groups was the same despite a 61% decrease in HO enzyme activity in the Hb + SnPP group after 60 h of O2. In addition, inhibition of HO activity with SnPP alone before O2 exposure did not augment the extent of hyperoxic lung injury. These results demonstrate that IT Hb induces lung HO-1 in the rat and protects against hyperoxia; however, the protection is not mediated by increased HO enzyme activity.
血红素加氧酶（HO）-1催化血红素分解，由氧化应激诱导，可能对氧化损伤具有保护作用。我们推测，肺内血红蛋白（Hb）诱导HO-1可保护大鼠免受肺氧中毒。通过蛋白质印迹分析，气管内（i.t.）给予Hb的大鼠在8小时时出现肺特异性HO-1诱导。然后，在暴露于100%氧气60小时之前，大鼠先用气管内生理盐水、Hb或Hb加HO-1抑制剂锡原卟啉（SnPP）预处理8小时。如较低的胸腔积液量和湿重与干重之比所示（P<0.01），Hb+O2组和Hb+O2+SnPP组动物的肺损伤均小于生理盐水对照组。尽管在氧气暴露60小时后，Hb+SnPP组的HO酶活性降低了61%，但两个Hb处理组的损伤改善情况相同。此外，在氧气暴露前单独用SnPP抑制HO活性并未增加高氧肺损伤的程度。这些结果表明，气管内给予Hb可诱导大鼠肺HO-1并预防高氧；然而，这种保护作用并非由HO酶活性增加介导。
