The Protective Effect Of Substance P On Hyperoxia-induced Lung Injury In Pretern Rats And ERK Signaling Pathway

Objective: To explore the effect of substance P on the repair of hyperoxia-induced lung injury in premature rats and the relationship of extracellular-signal regulated protein kinase( ERK) signaling pathway. Methods: According to the brood, sixty premature Wistar rats were divided randomly into 4 groups(n=15): group 1: air group; group 2: air with SP intervention group( rats in group 1 and group 2 were exposed in the container where the concentration of oxygen was 21%); group 3: hyperoxia injury group; group 4: hyperoxia injury with SP intervention group( rats in group 3 and group 4 were exposed in the container where the concentration of oxygen was 95%). Each group was divided into 3 subgroups according to the 3 time points of 3d, 7d and 14d( n=15). 5 rats of each subgroup were sacrificed and the lung tissues were collected at each time points for certain indicators to be monitored. Pathology of lung was examined with optical microscopy; Determination wet / dry weight ratio of the lung tissue; The content of SP in lung tissue was detected by radioimmunoassay; The content of MDA, SOD and GSH-Px in lung tissue was detected by ELISA; To observe the cells, apoptosis of lung tissue with TUNEL; To observe the cells, proliferation of lung tissue with PCNA; While p-ERK was detected by western blo. Results: The pathological of preterm rats, lung tissue which exposured in hyperoxia showed injury and edema. The W/D of rats in hyperoxia injury groups had increased(P<0.05). We compared the hyperoxia injury group with the air group. The content of SP was decreased(P<0.05); The content of MDA was increased(P<0.05); The content of SOD and GSH-Px were decreased(P<0.05); The number of TUNEL-positive cell was increased; The number of PCNA-positive cell was decreased. And the changes were more obvious with the extension of the exposure time. While treated with substance P the injury of preterm rats, lung tissue could be improved. The W/D had decreased(P<0.05); The content of SP was increased(P<0.05); The content of MDA was decreased(P<0.05); The content of SOD and GSH-Px were increased(P<0.05); The number of TUNEL-positive cell was decreased; The number of PCNA-positive cell was increased. The results of Western blot revealed that the expression of p ERK protein was higher in the hyperoxia injury group than that in the air group(P<0.05), and the expression of p-ERK protein was increased in time dependently. The comparison between the air group had no significant change(P>0.05). Conclusion: Hyperoxia can lead to imbalance of the oxidation / antioxidation system. Hyperoxia can lead the number of cells apoptosis to increased and the number of cells proliferation decreased. Ultimately.hyperoxia can lead to lung injury. All of the above changes are through up-regulating the ERK signaling pathway. The rats with SP intervention can alleviate oxidative damage in rat lung tissue by continue to up-regulating ERK pathway, and then the oxidative damage can be alleviated.