Effects Of Low Molecular Heaprin On Hypoxia Inducible FACTOR-1、Heme OXYGENASE-1 And Vascular Endothelial Growth Factor In Lung Tissue Of Rat Model With Chronic Obstructive Pulmoanry Disease

OBJECTIVE To investigate the effect of low-molecular-weight heparin on the expressions of hypoxia inducible factor-1(HIF-1), heme oxygenase-1(HO-1) and vascular endothelial growth factor (VEGF) in the lung tissue of rats with chronic obstructive pulmonary disease.METHODS Sixty Wistar rats were randomized to be divided to three groups;①control group:rats were administrated saline by intracheal instillation and were given subcutaneous injection of saline;②OPD model group:COPD model was set up by intratracheal instillation of lipopolysaccharide and smog exposure, normal saline was injected subcutaneously once a day as control;③LMWH intervened group:set up the COPD model the same way as above. Subcutaneous injection of Low molecular weight heparin (LMWH, Fragmin) was administrated to the rats once a day, starting from the day upon completion of the model. Blood gas analysis, bronchial alveolar lavage fluid (BALF), lung tissue histopathology change was observed. The expressions of hypoxia inducible factor-、heme oxygenase-1 and vascular endothelial growth factor were examined immunohistochemically. The relationships between the numbers of nutrophils and HIF-1, HO-1, VEGF respectively were analysed.RESULTS Compared with control group:the blood gas analysis of COPD model group and LMWH group were significantly severe, PaC02 were highly elevated, PaO2 were damaticly droped (P<0.05); the numbers of total cells and the numbers of nutrophlis in the BALF were significantly increased (P<0.05); MLI and PAA were highly enlarged, while MAN were decreased (P<0.05); the expressions of HIF-1, HO-1 and VEGF were significantly increased (P<0.05). Compared with COPD model group, the indicators of blood gas analysis, BALF, and pathological changes of the lung tissue in LMWH intervened group were milder, the expressions of HIF, HO-1 and VEGF decreased, and the difference had statistical significance(P<0.05). The present study showed exposure of cigarette smoke and LPS to rats induced characteristics similar to what observed in COPD patients. The relationship between the numbers of nutrophils in BALF and the expressions of HIF-1, HO-1 and VEGF were positively correlated (P<O.05).CONCLUSION HIF-1、VEGF and HO-1 all participate in the airway inflammation of COPD. LMWH can alleviate the inflammation process.