The Protection Experimental Study Of Heme Oxygenase 1 On ALI Rat Alveolar Epithelial Type Ⅱ Cell

Objective To study the protective effect of heine oxygenase-1(HO-1) on acute lung injury in rat alveolar epithelial typeâ…¡cell,and to investigate the protective effect of acute lung injury and acute respiratory distress syndrome.Methods Thirty-two male SD rats weighing 180-200g were randomly divided into 4 groups(n=8 each): group C(normal control group);group OA(injury control group);group OA+AS (aspirin pretreatment group);group OA+IX(zinc porphyrin IX pretreatment group).The aspirin was added in the food before mold in the group OA+AS(5mg/kg.d,two days). The specific inhibitors-IX zinc porphyrin was added in group OA+IX,the first dose of 20μmol/kg,subcutaneous injection molding 6h ago,and then to the same dose after 3h.All the rats were anesthesitized with 10%Chloral hydrate(0.35ml/100g).The 0.9% sterile NS(0.15ml/kg) was injected into the femoral vein in group C,and the oleic acid (0.15ml/kg) was injected into the remaining three groups.The internal carotid artery was isolated and the arterial blood gas were examined in 30min,60min,120 min time points.The rats were killed after 2 hours,at the same time,the centrifugal supematant of the blood was preserved below-70℃.The wet/dry(W/D)weight ratio and the expression of HO-1 protein of Lung tissue was determined.The ultrastructural changes of Alveolar epithelial typeâ…¡cell was observed.The HE staining and alveolar typeâ…¡epithelial cells(AEC-â…¡) ultrastructural changes was done form the lung tissue.Results (1) arterial blood gas:the statistically significant difference were found between the groups about the PO₂,PCO₂,PH,OI(PaO₂/FiO₂)(P＜0.05或P＜0.01).(2) lung wet/dry(W/D) weight ratio:the statistically significant difference were found between the groups about the W/D(P＜0.01).(3) the statistically significant difference were found between the groups about the SP-A in BALF and serum(P＜0.01).(4)In group C,the structure of lung tissue in optical microscope was clear,alveolar septal capillaries mild congestiving and expanding,bronchial alveolar part of the side partitions and a small amount of interstitial lymphocytic infiltrating.In group OA,the structure of lung tissue in optical microscope was disorder,Capillary in lveolar septal congestiving,bleeding and deceasing.In group OA+AS,the structure of lung tissue in optical microscope was little clear,alveolar intervals congestiving and expanding.In group OA+IX,the structure of lung tissue in optical microscope was unclear,and a high degree of alveolar septal capillaries see congestive expansion,and some alveolar edema fluid filled cavity,some see a large number of alveolar lymphocytes intervals and a small amount of neutrophil infiltration,we can see large and small coagulative necrosis of lung lesions.(5) lung tissue HO-1 protein expression:â‘ light microscopy study: the HO-1 in the bronchial and alveolar epithelial cells and alveolar macrophages were strongly positive expression in group OA+AS,and the expression was weaker than the group OA+AS in the group OA and OA+IX.It was weak positive expression in the group C.â‘¡Semi-quantitative:the statistically significant difference were found between the groups about IOD(P＜0.01).(6) AEC-â…¡ultrastructure:the shape are good,the microvilli,nucleus and lam ellar body are clearly visible in electron microscopy in group C.The AEC-â…¡is relatively irregular,cell degenerating or even collapsing,the cell surface Mv reducing intracytoplasmic LB emptying,arid some into the alveolar space in group OA.These changes are the most important in group OA+IX. Conclusions The high expression of HO-1 from aspirin-inducing has a protective effect on acute lung injury,the zinc porphyrin IX can inhibit HO-1 expression,so it can increase the acute lung injury induced by OA.The mechanism may be associated with iNOS/NO system and the interaction of the HO-1/CO.The ALI can cause the release of various inflammatory mediators and reactive oxygen species,AEC-â…¡injuring, pulmonary microvascular permeability increasing,and the surfactant synthesis and secretion is limited.So the HO-1 high expression has obvious protection from the AEC-â…¡.