| Objective: To investigate the effects of different doses of dexmedetomidine(DEX)on hyperoxia-induced acute lung injury(HALI)in Sprague–Dawley rats and apoptosis in order to provide a new reference medicine for clinical application of HALI and basic data for the clinical use of DEX.Methods: Sixty healthy male Sprague-Dawley(SD)rats were divided into five groups(n=12)by random number table method: group I(air+normal saline),group II(hyperoxia+normal saline),group III(hyperoxia+DEX 25?g/Kg.d),group IV(hyperoxia+DEX 50?g/Kg.d),group V(hyperoxia+DEX 100?g/Kg.d).Rats of group II-V were intraperitoneally injected DEX or normal saline at 30 minutes fefore modeling.The rats of group II-V were fed in the oxygen chamber in which the oxygen concentration was higher than 90 %,with the temperature maintained at 24-26 ?,humidity of 50-70 %,and CO2 concentration <0.5%.The oxygen was supplied constantly for 23.5 hours every day to the oxygen chamber which was opened for thirty minutes everyday at fixed time to add water,food and inject drug.6 rats were selected from each group above respectively at two experimental times which are after 48h(T1)and 72h(T2)for observation.After anesthesia,arterial blood gas analysis was performed to calculate the oxygenation index(OI)and the respiratory index(RI).The serum IL-6,IL-1b and TNF-a were measured by enzyme-linked immunosorbent assay(ELISA).Changes of lung tissue were observed and the lower right lung was taken to make HE staining.Use optical microscope to observe the pathology change and get the pathological score.The left lung was dealed by paraffin imbedding to detect apoptotic index of the lung tissue by the method of TUNEL.Results: 1.General status: Rats in group I reacted well at all times.After 12 h,rats in group II were observed a series of symptoms such as anorexia,refusal to drink,less activity,dull hair,accelerated breath rate.The mouths,noses,limbs,distal tails appeared cyanosis at different levels.The symptoms were more severe with prolonged hyperoxia.After 48 h,the phenomenon of high oxygen dependence was appeared gradually.The hemorrhagic secretions could be seen in the mouths and noses of a small number of the rats.Rats in group III had the similar performance with rats in group II.Rats in group IV and group V appeared calm after injecting drug without respiratory depression.The symptoms of anorexia,polypnea and cyanosis were relieved obviously.And the eneral status was better than rats in group II.No rats died among the five groups during the experiment.2.Changes of respiratory function:compare group I with group II at the same time phase,the OI of group II was significantly lower than that of group I while the RI was significantly higher than that of group I(all P<0.05).Make a comparison among group II-V at the same time phase,there was no significant difference in OI and RI between group II and III(all P>0.05).The OI in group IV and V was higher than that in group II,and RI was lower than that in group II(all P<0.05).There was no significant difference in OI and RI between group IV and group V(all P>0.05)3.Pathological observation of lung tissue3.1 General observation: The lung tissue of group I was pale pink,color uniformity,soft,no swelling,bleed.Group II : After 48 h exposured to hyperoxia,the colour and luster of the lung tissue became dark and with tumidness and several hemorrhagic spots.After72 h exposured to hyperoxia,the lung had been further injured.The lung tissue became dark red and the lesion distribution was not asymmetrical.Hemorrhagic spots increased and blended together,some even had yellow or hemorrhagic effusion.Rats in group III had the similar lung injury performance with rats in group II.At the same time phase,rats in group IV and group V had minor lung injury without pleural effusion than that in group II.3.2 Change under light microscope: The alveolar structure of group I was clear without obvious inflammatory cells.After 48 h exposured to hyperoxia,the lung tissue structure of group II was disorder,the alveolar walls integrity was destroyed,lung interval broadening appreciably with some inflammatory cell.Red blood cells aggregated and there was edema fluid in some alveolar space.After 72 h exposure to hyperoxia,the lung tissue structural lesion aggravated,even appeared diffuse pulmonary edema.Rats in group III had the similar lung tissue structural lesion with rats in group II.At the same time phase,rats in group IV and group V had significant minor lung injury than rats in group II.3.3 Pathological score of lung tissue: Group I and group II: At the same time phase,the pathological score of group II was significant higher than group I(all P<0.05).At T1 time phase,the group II and group III did not have significant difference of pathological score(all P>0.05).At T2 time phase,the pathological score of group II was significant higher than group III(P<0.05).The athological scores of group IV and group V were significantly lower than those of group II(all P<0.05).There was no significant difference between group IV and group V(all P> 0.05).4.The ELISA for TNF-a,IL-6,IL-1b in serum: Group I and group II:At the same time phase,the levels of serum IL-6,IL-1? and TNF-a in group II were significantly higher than those in group I(all P<0.05).There was no significant difference in IL-6,IL-1b and TNF-a between group II and III(all P>0.05).The results of group IV and group V were significant lower than those in group II and the difference has statistical significance(all P<0.05).There was no significant difference between group IV and group V(all P>0.05).5.Apoptosis index of lung : At the same time,apoptosis index of lung tissue was significantly higher in group II than that in group I(all P<0.05).At T1 time phase,there was no significant difference between group II and group III(P>0.05).At T2 time phase,the apoptotic index of group III was lower than that of group II(P<0.05).The apoptotic index of group IV and group V was lower than that of group II(all P<0.05),but there was no significant difference between group IV and group V(all P>0.05).Conclusion: 1.Continuous inhalation high concentration of oxygen(Fi O2>90%)can lead to lung tissue structure destruction and respiratory function damaged in rats.It also can decrease Oxygenation Index while rise Respiratory Index.The pathological manifestations includes pulmonary structural disorders,alveolar wall fusion,alveolar telangiectasia,alveolar septa widened,inflammatory cell infiltration,alveolar cavity visible pink exudate.Continuous injection of high concentration of oxygen for more than 48 h can be successfully established a typical HALI rat model.2.Persistent high concentration of oxygen exposure can lead to pulmonary inflammatory response,significant increase of inflammatory factor and apoptosis.50?g/Kg.d,100?g/kg.d of DEX intraperitoneal injecting can inhibit lung inflammation and injury,improve lung function,reduce lung cell apoptosis.DEX has protective effect on HALI. |
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