[Therapeutic effects of low molecular weight heparin and aspirin on acute lung injury in rat].
OBJECTIVE
To investigate the possible effects of nuclear factor-KappaB (NF-KappaB) activation on the expression of intercellular adhesion molecular-1 (ICAM-1) and P-selectin in murine acute lung injury (ALI) and assess the potential beneficial effects and mechanism of low molecular weight heparin (LMWH) and aspirin (ASA).


METHODS
Rat ALI model was reproduced by injection of lipopolysaccharide into tail vein. Sixty rats were divided randomly into four groups (n=15): normal control group, ALI group, LMWH group and ASA group. The change in NF-KappaB activity in the lung to show its relation with ICAM-1 and P-selectin was observed by immunohistochemistry.


RESULTS
Compared with normal control group, the activity of NF-KappaB and the expression of ICAM-1 and P-selectin increased significantly in the lung tissue of ALI group (all P<0.05). Compared with ALI group, the level of NF-KappaB activity and the expression of ICAM-1 and P-selectin were obviously down regulated, and also the pathological lesion and inflammatory response of lung were improved in LMWH and ASA groups. However, the therapeutic effects of ASA were stronger than those of LMWH (all P<0.05).


CONCLUSIONS
NF-KappaB activation plays an important role in ALI. NF-KappaB takes part in the activation of many kinds of inflammatory cells such as neutrophil, endothelial cells and so on, and it adjusts the genetic expression of ICAM-1 and P-selectin. LMWH and ASA show their beneficial effects on lung injury in both functional and morphological aspects. But the mechanism is different. LMWH can indirectly inhibit the activation of NF-KappaB, improve lung microcirculation and decrease the adhesion of neutrophil and platelet. ASA plays the role as an inhibitor of NF-KappaB activation.
Luan
Zheng-gang
ZG
Department of Intensive Care Unit, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China.
Nala
Pulu
P
Zhang
Zhi-dan
ZD
Ma
Xiao-chun
XC
D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D006495:Heparin, Low-Molecular-Weight; D016328:NF-kappa B; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D001241:Aspirin