Effects Of Rapamycin On Pulmonary Histopathology And MTOR Signaling Pathway In Transfution-related Acute Lung Injury Rat Model

Objective Based on a transfution-related acute lung injury?TRALI?SD rat model,to detect the activation of mTOR signaling pathway in the rat lung tissues.And to investigate the effects of rapamycin on the main symptoms,pulmonary histopathological changes and the expressions of mTOR signaling pathway down-stream proteins p70s6k/p-p70s6k in the TRALI rat model.^[23]Methods Part 1:Effects of rapamycin on the main symptoms and pulmonary histopathology in TRALI rat model 30 SD rats were randomly divided into TRALI group,Rapamycin group and Control group.TRALI group:treated LPS 2 mg/kg by intraperitoneal injection 1 hour before removed 1ml rat blood and then treated human type AB plasma by vein injection.Rapamycin group:treated rapamycin 10 mg/kg for consecutive 3 days by intragastric administration and then TRALI model made.Control group:treated by intraperitoneal injection and vein injection of saline which volumes were equal to TRALI group.Then the other procedures were the same as TRALI model.^[23]The main symptoms,pulmonary histopathological changes by HE stainning were evaluated.And then through the lung tissue grading criteria score for rat lung tissues of each group.^[23]Part 2:Effects of rapamycin on the exprssions of mTOR signaling pathway down-stream proteins p70s6k/p-p70s6k in TRALI rat model The establishment of rat models were the same as part 1.Preparation of lung tissue homogenates,the expressions of mTOR signaling pathway down-stream proteins p70s6k/p-p70s6k in the rat lung tissues of each group were examined by Western blot.^[23]Results Part 1:Effects of rapamycin on the main symptoms and pulmonary histopathology in TRALI rat model There were significant differences between TRALI group and control group in the main symptoms?p<0.05?^[23].But in rapamycin group the administration of rapamycin has no significant difference compared with TRALI group?p>0.05?^[23].There were significant differences between the scores of pulmonary histopathology of TRALI group?9.30±2.21?and control group?2.60±1.82??t=5.83,p<0.05?^[23].And the scores of pulmonary histopathology were significantly ameliorated in rapamycin group?6.60±1.78?compared with TRALI group?t=-4.08,p<0.01?^[23].But still higher than control group?t=3.01,p<0.01?^[23].Part 2:Effects of rapamycin on the exprssions of mTOR signaling pathway down-stream proteins p70s6k/p-p70s6k in TRALI rat model There were no significant differences of the expressions of total protein p70s6k between TRALI group,Rapamycin group and control group?p>0.05?^[23].The expressions of phosphorylation protein p-p70s6k in TRALI group were significantly increased compared to control group?t=-7.22,p<0.001?.And compared with TRALI group,the expressions of p-p70s6k in rapamycin group were significantly blocked?t=-31.50,p<0.001?,and even lower than control group?t=-30.16,p<0.001?.^[23]Conclusion Administration of rapamycin ameliorated the pulmonary histopathology severity of TRALI on a certain degree.But administration of rapamycin had a limited effect in the main symptoms of TRALI^[23].The mTOR signaling pathway was activated in the process of TRALI.Administration of rapamycin significantly inhibited the over-activation of mTOR signaling pathway in TRALI^[23].