| Objective To investigate the conservation effective and mechanism of gabexate mesilate(GM) and ischemic preconditioning(IPC) to lung that received ischemia /reperfusion(I/R), and the protective mechanism to lung I/R injury of GM combining with IPC.Methods Thirty healthy New Zealand white rabbits were randomly divided into five groups.①S ham-operated group(group S, n=6), only the left pulmonary hili were anatomised, without obstruction of the left pulmonary blood flow and ventilation, Normal saline(NS)(10ml/h) was pumped through veins.②Ischemia /Reperfusion group(group I/R, n=6), the left lungs of rabbits were rendered ischemia by snaring the left pulmonary hili for 60 minutes followd by 120 minutes reperfusion, NS(10ml/h) was administered intravenously 60 minuts before ischemia.③Gabexate mesilate group(group GM, n=6), the left lungs were rendered ischemia for 60 minutes followed by 120 minutes reperfusion, and 10mg/(kg?h) (10ml/h) GM was administered intravenously 60 minutes prior to ischemia.④Ischemic preconditioning group(group IPC, n=6), 10ml/h NS was pumped through veins 60 minutes before ischemia, waiting 35 minutes, and then snaring the left pulmonary hili 10 minutes followed by reperfusion 15 minutes(IPC), the rest process was the same with group I/R.⑤Gabexate mesilate plus ischemic preconditioning group(group GM+IPC, n=6), 10mg/(kg?h) (10ml/h) GM was administered intravenously 60 minutes prior to ischemia, the rest process was the same with group IPC. After experiments, protein contents in blood were measured, protein contents and NE in bronchoalveolar lavage fluid(BALF) were determined, and calculated the lung permeability index (LPI)(LPI=BALF prot /serum prot) . the levels of TNF-a, MDA, MPO, SOD, the left lung dry-to-wet weight ratio(W/D) and the pathologic changes of samples of left lung tissue were examined.Results Compared with group I/R, MPO, MDA were lower( P< 0.05), NE, TNF-a, W/D and IPC were significantly lower( P< 0. 01), SOD activity was higher( P< 0.05) in group GM and group IPC; Compared with goup GM and goup IPC respectively, MDA, MPO, TNF-a, W/D and LPI were lower( P< 0.05), SOD activity was higher( P< 0.05) in group GM+IPC, NE in group GM+IPC was lower than NE in group IPC( P< 0.05), was lower significantly( P< 0.01) than NE in group GM ; all parameters in group GM+IPC were significantly lower( P< 0.01) than which in group I/R; there was not significant difference between group GM and group IPC ( P > 0. 05); pathologic evaluations revealed less inflammatory cells infiltration, milder pulmonary interstitial edema and alveolar injury in group GM and group IPC than in group I/R, the injury in group GM+IPC was the slightest.Conclusions1. In this study, we traped the whole left pulmonary hili with silk , and then tightened the thread to obstruct the left pulmonary blood flow and ventilation, and opened the ring to recover the blood flow and ventilation some time later, this was a simple and effective methed to establish the model of ischemia reperfusion in vivo rabbit.2. The main mechanism of lung I/R injury may be the accumulation and infliltration of neutrophil(PMN) in the lung, which mediated the production of inflammatory factors, oxygen free radicals(OFR), lipid mediators and proteases, et al, they connected with calcium ion overload, energy metabolic disorder and microcirculatory disturbance caused the acute lung injury in common, besides all factors interacted and strengthened each other, which formed a vicious circle.3. GM and IPC all can reduce rabbits'lung I/R injury by inhibiting the production of inflammatory cytokines and OFR, increasing antioxidant capacity, reducing capillary and alveolar infiltration, inhibiting proteinase and calcium overload etc.4. GM and IPC have lots of similarities in reducing lung ischemia-reperfusion injury, the combination of GM and IPC can play a synergistic or additive effect, which can prevent and reduce the lung ischemia-reperfusion injury better. |
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