Effect Of Rapamycin On The Expression Of MTOR And P70S6K In Septic Lung Injury

Objectives:Investigate the effect of rapamycin on the expression of mTOR and p70S6 K in septic acute lung injury.Methods:In this study,the acute pulmonary injury model of sepsis was established by injecting LPS(5mg/kg)into the tail vein,and rapamycin(2mg/kg)was given as an intervention.Ninty mouse were randomly divided in 3 groups(saline control group,LPS group,rapamycin group),to observe the changes of the disease and the pathological changes of lung tissues at different time periods of 1,3,5,7,9 days.Enzyme-linked immunosorption(ELISA)was used to detect leukocyte mediated-l(IL-1),tumor necrosis factor-?(TNF-?),leukocyte mediated-l0(IL-10)and inflammatory cells in alveolar lavage fluid.Serum glutathione peroxidase(GSH-px),superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by experimental kit,lung tissue mTOR and p70S6 K were detected by real-time quantitative PCR.Results:The protein content in the alveolar lavage solution of the LPS group and the rapamycin group was significantly higher than that of the control group for 1-9 days,reaching a peak at 5 days and then gradually decreasing,with statistical difference(P<0.01).The protein content in the alveolar lavage solution of rapamycin was lower than that of the LPS group for 1-9 days,with statistical difference(P<0.05).The contents of MDA,IL-6,IL-10 and TNF-? in the serum of the LPS group and the rapamycin group were higher than those in the control group on days 1 to 9,reaching a peak on days 3 and gradually decreasing(P<0.01).The contents of MDA,IL-6,IL-10 and TNF-? in the serum of the rapamycin group on days 1 to 9 were lower than those in the LPS group,the contents of IL-10 were higher than those in the LPS group(P<0.05).The content of GSH-px in the LPS group and the rapamycin group was lower than that in the saline control group for 1-9 days,reaching the minimum value for 5 days and gradually increasing(P<0.01).The content of GSH-px in the serum of the rapamycin group was higher than that in the LPS group for 1-9 days(P<0.05).SOD content in LPS group andrapamycin group was lower than that in the saline control group for 1-9 days,reaching the lowest level for 3 days(P<0.01),while serum SOD content in the rapamycin group was higher than that in the LPS group for 1-9 days(P<0.05).The value of W/D(wet-dry ratio)in the rat lung tissues of the LPS group and the rapamycin group at day 1 to 9 was higher than that of the control group,reaching a peak at day 3 and then gradually decreasing,with statistically significant difference(P<0.01).The value of W/D in the lung tissues of the rapamycin group at day 1 to 9 was lower than that of the LPS group(P<0.05).The expression levels of mTOR and p70S6 K in the lung tissues of the LPS group and the rapamycin group were increased and peaked at 5 days(P<0.01),while the expression levels of m TOR and p70S6 K in the lung tissues of the rapamycin group were decreased at 1-9 days(P<0.05).Conclusions:Rapamycin can inhibit the expression of mTOR and p70S6 K,reduce oxidative stress injury,balance inflammatory cytokines,and achieve the protective effect on septic acute lung injury.