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Objective: through the use of lung ischemia-reperfusion injury (lung ischemic-reperfusion injury, LIRI) animal model of hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) in lung ischemia-reperfusion injury in a sense, to further reveal the mechanism of ischemia-reperfusion injury, ambroxol ambroxol drug intervention in lung ischemia-reperfusion injury in rats. : Blocking hilar 60 minutes to 6 hours reperfusion to establish rat lung ischemia-reperfusion injury in animal models. 50 female Wistar rats were randomly divided into five groups, the blank control group (Control group): right animal for any treatment, ventilator-assisted direct anesthetic after thoracotomy lung tissue specimens in this group as each group before surgery blank; ischemia-reperfusion injury group (IR): tracheostomy, mechanical ventilation, a left thoracotomy, free left lung door, blocking the chest open occlusion clamp off after 60min, since open hilar blocking clamp began six hours after the animals were sacrificed and lung specimens; ischemia-reperfusion - surgical control group (IR-Sham group): tracheotomy, ventilator-assisted left thoracotomy, free left lung door, do not block the sternal closure, since the closed chest began six hours after the animals were killed, the lung specimens; pure ischemia group (I): tracheotomy, ventilator-assisted the left thoracotomy free door of the left lung, blocking 60min after blocking clamp does not open, direct lung specimens; ischemia - surgical control group (Ⅰ-Sham group): tracheotomy, ventilator-assisted left thoracotomy, free left lung door, not blocking the lung specimens . The groups design into 10 rats, if any, the death of the trial period, you continue to make up to 10. The end of the experiment, the removal of the lung tissue, measured lung wet / dry weight ratio (W / D), made of homogenate measured lung tissue IL-1β, TNF-α, histopathological, immunohistochemical staining with image analysis techniques, lung histopathological changes, VEGF and HIF-1α expression. Then take the 40 female Wistar rats to evaluate Mucosolvan ischemia-reperfusion injury in the lung protective effect. Grouped as follows: (1) blank control group (Control group): right animal for any treatment, no ventilator-assisted, direct anesthetic after thoracotomy lung tissue specimens, this group as a blank control (2) in each group preoperative ischemia the perfusion - surgery control group (IR-Sham group): tracheotomy, ventilator-assisted left thoracotomy, the free door left lung, not blocking, closed chest since closed chest began, through the femoral vein to the syringe pump continues venous input the saline (5ml/kg/h), 6 hours after the animals were killed, the lung specimens (3) ischemia-reperfusion injury group (IR): tracheotomy, ventilator-assisted left thoracotomy, free left to open blocked hilar, blocking 60min pliers, closed chest, since open hilar occlusion clamp start, continuous intravenous infusion of normal saline (5ml/kg/h) via the femoral vein to the syringe pump, 6 hours after the animals were killed, The lung specimens (4) Mucosolvan intervention group (Ambroxol): tracheostomy, mechanical ventilation, a left thoracotomy, free left lung door, blocking clamp open blocked after 60min, closed chest, since open hilar resistance start off the clamp, input via the femoral vein continuous intravenous syringe pump the Mucosolvan the solution (5ml/kg/h), 6 hours after the animals were killed, and the lung specimens. The groups design into 10 rats, if any, the death of the trial period, you continue to make up to 10. The end of the experiment, the removal of the lung tissue measured lung tissue wet / dry weight ratio (W / D), made of homogenate measured lung tissue IL-1β, TNF-α, MPO. Histopathological, immunohistochemical staining technology and image analysis techniques to observe the pathological changes of lung tissue, VEGF and HIF-1α expression. Results: The lung tissue wet / dry weight: Control group, IR-Sham, I, group data differences between groups of I-Sham group and IR group with a statistically significant difference (P lt; 0.05); lung tissue IL-1β, TNF -α levels, IR group were significantly higher than the Control group, the IR-Sham, I, group Ⅰ-Sham group (P lt; 0.05), but no significant difference between Group I with the IR group. Histopathologically observed IR lung tissue congestion and edema and inflammatory cell infiltration is more pronounced over the other four groups. Lung tissue HIF-1a protein expression levels between the two groups overall data difference was statistically significant (P lt; 0.05), between any two groups found in IR group the Ⅰ-Sham group, IR-Sham, Ⅰ group difference was not statistically significant. The overall difference between the relative expression levels of VEGF in lung tissue group was statistically significant (P lt; 0.05) between the two groups found that the IR group were in Group I, Ⅰ-Sham group difference was statistically significant (P lt ; 0.05), but with the Control group, the difference between the IR-Sham group was not statistically significant. (P gt; 0.05). Ischemia-reperfusion injury in the lung tissue of HIF-1a, VEGF gene expression analysis: Pearson correlation test, ischemic reperfusion lung tissue HIF-1a, VEGF expression levels significantly correlated, suggesting LIRI Period 2 the possibility of interaction or mutual regulation between the expression of the kinds of factors. Ambroxol intervention group measured by high-dose ambroxol intervention, IL-1β, TNF-α content and MPO activity was significantly lower than non-drug interventions ischemia-reperfusion injury group. W / D of lung tissue was significantly lower, Pa02 was significantly higher. Combined with light Histological found the Mucosolvan intervention alveolar septal edema, intrapulmonary bleeding compared with reperfusion injury group was significantly reduced. Conclusion: HIF-1α, VEGF involved LIRI; protective effect of ambroxol on lung ischemia-reperfusion injury.
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