Effect Of Caffeine On Hyperoxia Lung Injury In Preterm Rats And Its Relationship With P38MAPK Signal Pathway

Objective: To study the effect of caffeine on hyperoxic lung injury of premature rats and its relationship with P38 MAPK signal pathway。Methods: Sixty Wistar premature rats were divided into 4 groups(n=15)according to the random number table method: air + normal saline group(A+N group),air +caffeine group(A+C group),hyperoxia + normal saline group(H+N group),and hyperoxia + caffeine group(H+C group).H+N group and H+C group were continually exposed to high oxygen environment(oxygen concentration was 60%).For A+C group and H+C group,the premature rats were injected with caffeine of29mg/(kg ? d)into their peritoneal cavities after birth.For A+N group and H+N group,the premature rats were injected with the same volume normal saline into their peritoneal cavities.In each group,the lung tissues of five premature rats were randomly selected on the third,seventh and fourteenth day respectively.The pathological changes of lung tissue,radiated alveolar count(RAC)and collagen content in lung tissue were observed under a light microscope.The wet/dry ratio(W/D)was measured.immunohistochemistry was used to detect the distribution of phosphorylated p38 MAPK in lung tissue.The content of phosphorylated p38 MAPK and p38 MAPK protein was detected by western blot(WB)。Results:Compared with the A+N and A+C groups,the premature rats in the H+N and H+C groups showed varying degrees of inflammation in the lung tissues on the 3rd,7th,and 14 th days,mainly showing a small amount of red blood cells and fluid exudation.Pathological changes such as pulmonary edema,and pulmonary inflammation changes gradually become obvious with the prolonged hyperoxia exposure time.On the 14 th day,the inflammatory exudation of lung tissue decreases,and the pulmonary interstitial thickens with mild fibrosis.After caffeine intervention under hyperoxia exposure,lung tissue inflammation was significantly reduced than before.Compared with A+N and A+C groups,the RAC value of the lung tissue of the H+N,H+C group was significantly lower than that of the A+N,A+C group(P<0.05),the W/D ratio and the lung tissue collagen content were significantly increased(P<0.05),coffee After the intervention,the RAC value,W/D ratio and lung tissue collagen content were significantly improved(P < 0.05).The results of immunohistochemistry showed that the number of phosphorylated p38MAPK-positive cells in the lung tissues of premature rats in the H+N and H+C groups increased and distributed widely,especially in a large number of infiltrating inflammatory cells.The number of phosphorylated p38MAPK-positive cells was higher after caffeine intervention.Before reducing.Western Blot results showed that the phosphorylated p38 MAPK protein content in the lung tissue of premature rats on the 3rd,7th and 14 th day in the H+N and H+C groups was significantly higher than that in the A+N and A+C groups(P < 0.05).The expression of phosphorylated p38 MAPK protein decreased after caffeine intervention(P<0.05).Conclusion: Hyperoxia may activate the p38 MAPK signaling pathway to cause lung inflammation and form pulmonary fibrosis,and caffeine may reduce the expression of p38 MAPK,reduce the occurrence of inflammatory reactions in the lungs under hyperoxia exposure,and further protect lung tissue.