[Prophylaxis against ventilator-induced lung injury by Ambroxol].
OBJECTIVE
To investigate the protective effect of Ambroxol on ventilator induced lung injury (VILI) of rats.


METHODS
30 healthy SD rats were randomly divided into three groups: group A was served as control group (n = 10, V(T) 8 ml/kg), group B received large V(T) ventilation (n = 10, V(T) 40 ml/kg), group C received large V(T) ventilation with pre-treatment of IP ambroxol. The contents of protein, TNF-alpha, IL1-beta, IL-8 in BALF and MDA, SOD, GSH levels in the homogenate of the rat lungs were assayed respectively. Total white blood cells in BALF were counted; The severities of lung injury of the three groups were assessed under a light microscope.


RESULTS
The albumin and total protein contents in BALF were significantly higher group A than in groups B and C. A large quantity of WBCs infiltration were found in BALF of group B, while the amount of WBCs were decreased in group C. TNF-alpha, IL-1beta and IL-8 level in BALF of group B were 101.6 pmol.L(-1).mg(-1) Pr +/- 37.4 pmol.L(-1).mg(-1) Pr, 0.47 microgram.L(-1).mg(-1) Pr +/- 0.14 microgram.L(-1).mg(-1) Pr and 2.02 microgram.L(-1).mg(-1) Pr +/- 0.49 microgram.L(-1).mg(-1) Pr, respectively. MDA, one of the parameters reflecting the extent of oxidative reaction, were produced profoundly in the lungs of group B, but the local levels of SOD, which reflects the ability of antioxidation, were decreased significantly in group B. There existed significant differences of the above parameters between group B and group A. Ambroxol could significantly decrease the locally produced TNF-alpha and inhibit the oxidative reactions, and increase the locally antioxidative potency. Severe acute lung injuries were detected in group A by histological examination and the extent of injury was much lighter in group C than in group B.


CONCLUSIONS
Locally increased inflammatory cytokines formation and the imbalanced oxidative/antioxidative reaction play important roles in the pathogenesis of VILI. Ambroxol has an obvious protective effect on VILI through its antioxidant/anti-inflammation potent.
Zhang
B
B
Department of Respiratory Diseases, General Hospital of PLA, Beijing 100853, China.
Liu
Y
Y
D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid; D005100:Expectorants / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha; D012122:Ventilators, Mechanical / Q000009:adverse effects*
D001798:Blood Proteins; D005100:Expectorants; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000551:Ambroxol; D007371:Interferon-gamma; D013482:Superoxide Dismutase; D005978:Glutathione