[Preventive effects and mechanism of heme oxygenase-1 activation on acute respiratory distress syndrome in rats].
OBJECTIVE
To explore the possible mechanism of heme oxygenase-1 (HO-1) induction for its protective effects on acute respiratory distress syndrome (ARDS).


METHODS
The production of HO-1 was induced by hemoglobin (Hb) injection into oleic acid (OA) induced ARDS rats. Western blot and RT-PCR techniques were used to observe the induction of HO-1 in vivo. Both the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). Combined with blood gas analysis and other indexes, the effect of HO-1 on ARDS could be clearly manifested.


RESULTS
The expression of HO-1 mRNA was increased significantly 16 h after Hb injection, and the protein expression of HO-1 was also obviously increased 24 h later (P < 0.01). The levels of TNF-alpha and IL-8 in both serum and BALF were significantly lower in Hb + OA group than in OA group (P < 0.01). Arterial blood PaO(2), oxygen saturation, and oxygenated index in Hb + OA group [(56.28 +/- 6.71) mm Hg, (79.53 +/- 5.82)%, and (258.81 +/- 29.37) mm Hg respectively] were higher than in OA group [(35.08 +/- 4.59) mm Hg, (55.80 +/- 12.76)%, and (167.86 +/- 21.94) mm Hg]. Lung wet and dry weight, and pathological changes were also improved.


CONCLUSIONS
The production of HO-1 was successfully induced by hemoglobin in vivo. Protective effects of HO-1 on ARDS might be related to the decreasing in inflammatory factors, such as TNF-alpha and IL-8.
Chen
Jing
J
Research Center of Occupational Medicine, the Third Hospital of Peking University, Beijing 100083, China.
Zhao
Jin-yuan
JY
Wang
Guang-zeng
GZ
D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006454:Hemoglobins / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D006454:Hemoglobins; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019301:Oleic Acid; D051547:Heme Oxygenase-1