Effects Of Using Dexamethasone In Different Time On Injury Lung In Neonatal Rats Which Of Hyperoxia

Objectivs(1) To provide basis for investigating chang of lung structure with prolonged hyperoxia by observing structural changes in neonatal rats with different age. (2) To observe the effects on the lung morphology changes and growth status of normal neonatal rats after prolonged hyperoxia-exposed for establishing bronchopulmonary dysplasia (BPD) model in neonatal rats. (3) To study the effects of used dexamethasone in different time on lung pathological morphology changes and growth development in neonatal rats which injury of hyperoxia , in order to providing the theoretical reference of whether can use dexamethasone to prevent and cure BPD.MethodsThe Wistar neonatal rats was designed in eight groups by random including:7st d and 14st d air group (Ⅰa andⅠb group);7st d hyperxia group which prolonged exposed 95%oxygen for 7 days (Ⅱa group)and 14st d hyperxia group which bred in the air for 7 days after hyperoxia-exposed for 7 days (Ⅱb group);hyperxia group with Early dexamethasone group which give dexamethasone from 1.5ug/g for 3 days to 0.75ug/g for 4 days i.p qd on the first day of oxygen (Ⅲa group) ,and NS group which use NS instead (Ⅲb group). Later dexamethasone group (Ⅳa group) which give dexamethasone from the day leave oxygen to 14st day, the doses as well as early dexamethasone group, and NS group which use NS instead (Ⅳb group). Body weight, general situation and the death number of rats were recorded. Observe the pulmonary general pathology classification and lung morphometric analysis were undertaken according to HE staining.Judge the degree of pulmonary edema, alveolarization block and pulmonary fibrosis from lung coefficient calculation , alveolar interval thickness ,radical alveoli count (RAC)and pulmonary fibrosis Stocker score. Results(1)The air group rats growth is good. The lung morphometric analysis in 7th day showed thick septa and walls of alveoli and fewer alveoli. In 14th day, the septa and walls of alveoli became thin, alveoli showing large. There have significant differences in RAC and alveolar interval thickness between the two air groups (P<0.05). (2) The hyperxia group rats showing progressive serious oxygen dependence and respiratory insufficiency symptoms after exposed 95% oxygen 3 days later. The general station is worse than that of the air group. The weight growth in the hyperxia group is slower and the rate of weight growth is obviously decrease than that of the air group (264.76±27.98% Vs 396.94±41.67%,P<0.05). The 7st d hyperxia group rats displayed the septa dedma and thicker walls of alveoli , alveolar interstitial cells increaed , there was a few inflammatory cells and blooding cells exuded out in the alveoli and interstitial. The lung injury was continue and there was two rats died after stop breathing oxygen. The 14st d hyperxia group rats showed alveolar septa was obviously thicker, and the secondary septum decreased , the alveolar structure showed simple and had fewer and larger alveoli. RAC of hyperxia group rats(8.36±1.28) was significantly lower than that of neonatal rats in air group(12.71±1.79), the degree and incidence of pulmonary fibrosis were obviously increased. (3) The general situation of early dexamethasone group rats was the worst and the weight growth is the slowest of all groups. There were eight rats happened convulsions after unexposed oxygen and six rats died. The pulmonary general pathology classification was the mostlyⅢ,Ⅳ,Ⅴlevel. The degree of pulmonary edema, alveolarization block and pulmonary fibrosis were the most serious. There have significant differences in lung coefficient calculation, RAC, alveolar interval thickness and pulmonary fibrosis Stocker score between the early dexamethasone group and the NS control group (P<0.05). (4) The general situation of the later dexamethasone group was better and the growth increased faster than hyperxia group and NS comtrol group. The pulmonary general pathology classification of the later dexamethasone group was the mostlyⅡ,Ⅲlevel. The later dexamethasone group seemly lung injury is lighter, but there have not significant differences in lung coefficient calculation, RAC, alveolar interval thickness and pulmonary fibrosis Stocker score between the later dexamethasone group and the NS control group (P>0.05).Conclusions(1) The lung of the neonatal rat is still in the continuous development stage after birth. Neonatal rats exposed to 95%oxygen for 7 days may cause hyperxia lung injury and the lung damage continue serious after stop oxygen (2) Early use dexamethasone has no action to prevent BPD happen, instead it may aggravated the hyperxia lung damage. (3) Although there was no significently change of pulmonary structured exception after use dexamethasone later, but the general situation and rat growth improved. (4) Because of the clinical habit of dexamethasone use dose and use frequency, we suggest don`t use dexamethasone as prophylaxis for BPD, we should use dexamethasone therapy BPD in the late stages, and during the treatment process,we should use dexamethasone as small doses and short treatment as possible.