| Background: Drowning is an important public safety problem.It is the third leading cause of accidental death which causes about 50 million deaths in the world every year.Acute lung injury(ALI)is one of the most common complications in drowning patients.The osmotic pressure of seawater is more than three times that of the plasma.Once inhaling seawater,the hypertonic seawater cause serious damage to the lung tissue,and the components of blood also enter into the lung tissue,causing pulmonary edema,pulmonary hyperemia and hypoxemia.We found the red blood cells infiltrated into the lung tissue and were degraded into heme by macrophages.If heme,a proinflammatory stimuli,can not be cleared in time,it would cause oxidative stress and aggravate lung injury.HO-1 is an inducible heme oxygenase,which is induced by oxidative stress and has the effect of anti-inflammatory and antioxidant.HO-1 is also an enzyme which degradates heme into biliverdin,ferrous iron and carbon monoxide.Objective: 1.To establish an animal model of ALI induced by seawater aspiration;2.To explore the effect of HO-1 in the self-repair of ALI induced by seawater aspiration.Experimental methods: The mice were immersed in artificial sea water with a depth of 6cm for 28 s(water temperature: 25±2℃)to make animal model of ALI caused by seawater aspiration.Immediately after removal,the cardiac resuscitation was carried out quickly and the recovery of spontaneous circulation was observed.The recovery was abandoned when it was ineffective after 5 min.The lung wet/dry ratio and blood gas analysis were detected in the normal group,the death group and the 15 min group(4 mice in each group).The pathological changes of lung tissue and CT images were observed at different time points in the survival mice after drowning.The content and activity of HO-1,the activity of SOD and the content of MDA in the survival mice were detected.The mice were given the inhibitor of HO-1(zinc protoporphyria,ZnPP)and three days later,the pathological changes of lung tissue were observed and the content and activity of HO-1 and the expression of transforming growth factor beta 1(TGF-β1)were detected.At the same time,ferric ion was detected by Prussian blue staining.Experimental results: The data of blood gas analysis showed that there were severe anoxia,hypercapnia and metabolic acidosis in drowning mice.Compared with the normal group,the lung pathological morphology and CT images showed that lung injury were more serious in the 15 min,30 min,1 h,3 h and 6 h after drowning,and the lung injury was the most serious in the 1 h after drowning,and then gradually recovered after 3 days.After drowning,the activity of SOD decreased and the content of MDA increased.After 1 h,the activity of SOD increased and the content of MDA decreased.After 3 days,the MDA content and SOD activity tended to normal level.When compared with the normal group,there was no statistical difference about SOD activity in Seawater group,indicating that the oxidativestress of lung injury was alleviated..After drowning,the content and activity of HO-1 in lung tissue increased obviously and could last to the third day.After ZnPP was subjected into the mice by intraperitoneal injection,the content of HO-1 decreased and the activity was inhibited.Compared with the seawater group,the Prussian blue stain was negative in the Seawater+Zn PP group,indicating that the ability of HO-1 about catalyzing the degradation of heme reduced;compared with the seawater group,the content of TGF-β1 in ZnPP group also decreased and the pathological damage of lung tissue was aggravated;The results of Sirius red and Masson staining showed that no pulmonary fibrosis appeared in the day 3 and 7 after drowning,indicating that the increase of TGF-beta 1 may contribute to the ideal repair of lung injury.Conclusion: HO-1 play an important protective role in the self-repair of ALI induced by seawater. |
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