Expression And Mechanism Of Milk Fat Globule Epidermal Growth Factor-8(MFG-E8)in Young SD Rats With Acute High Altitude Lung Injury

Objective: To explore the protective effect of milk fat globular epidermal growth factor-8(MFG-E8)on the development of acute high altitude lung injury in children and its molecular mechanism by establishing a young rat model of high-altitude lung injury in SD rats.Research methods: High-altitude lung injury model was established in 21-day-old SD rats and divided into 4500-meter altitude hypoxia group(H group,H12 h,H1d,H2 d,H3d,H5 d,H7d);Plain normal oxygen group(N group);High altitude hypoxia+rm MFG-E8 supplement group(20 μ g/kg)(group R);Observe the activity of rats after modeling,record the water content of lung tissue of rats in each group,HE pathological staining,Western blot method to detect the protein expression of MFG-E8,immunohistochemistry staining to detect the location and expression of MFG-E8.After pretreatment with rm MFG-E8,the effects of MFG-E8 on rats with high altitude lung injury were detected,and the levels of inflammatory factors(IL-6,IL-1β,TNF-α)in lung tissue were detected by enzyme-linked immunosorbent assay,The level of oxidative stress(SOD,MDA)in lung tissue,the expression level of BAX,BCL-2,p-AKT,AKT protein by Western blot,and the apoptosis of lung tissue by TUNEL apoptosis detection kit;.Graph-Pad Prism 9 software was used to analyze the experimental data,and P<0.05 indicated that the difference was statistically significant.Results: 1.The expression of MFG-E8 decreased significantly during the progression of acute high-altitude lung injury,and then gradually recovered,which may be involved in the injury and adaptation of high-altitude lung injury.2.Supplementing exogenous rm MFG-E8 can enhance the anti-inflammatory effect of rats under acute hypoxia,and can down-regulate IL-6 and IL-1β,TNF-α The level of inflammation decreased;By increasing the activity of SOD and reducing the level of MDA,it suggests that it has the effect of antioxidant stress.3.rm MFG-E8 shows anti-apoptotic effect by up-regulating Bcl-2 and down-regulating BAX protein level.4.Supplementing exogenous rm MFG-E8 can promote AKT phosphorylation,and MFG-E8 may play a protective role in alleviating lung injury through PI3K/AKT signal pathway.Conclusion: 1.The rat model of high altitude lung injury disease can be successfully established through the simulated low pressure and hypoxia chamber at high altitude;2.The level of MFG-E8 in the lung tissue of rats with acute high altitude lung injury decreased sharply within one day,and then gradually recovered,which may be involved in the repair of high altitude lung injury;3.Pretreatment with rm MFG-E8 can reduce the degree of lung tissue injury,reduce the level of inflammatory factors,reduce oxidative stress reaction and apoptosis of tissue cells in high altitude lung injury.4.MFG-E8 may play a protective role through PI3K/AKT pathway.