雷帕霉素干预TRALI大鼠肺组织mTOR信号通路下游蛋白p70s6k/p-p70s6k表达与肺病理变化研究

Effects of rapamycin on expressions of m TOR down-stream proteins p70s6k/p-p70s6k and pulmonary histopathological changes in transfusion-related acute lung injury rat model

目的建立SD大鼠输血相关急性肺损伤(TRALI)模型,探讨雷帕霉素干预TRALI大鼠肺组织m TOR信号通路下游蛋白p70s6k/p-p70s6k表达与对肺损伤病理变化的影响。方法 SD大鼠30只随机分成3组(10只/组),TRALI模型组:LPS 2 mg/kg腹腔注射+人血浆5 m L/kg静脉注射;雷帕霉素干预组(Rapa组):Rapa 10 mg/kg连续3 d灌胃+TRALI模型;对照组:假手术处理。观察各组大鼠临床症状、肺组织病理变化及p70s6k/p-p70s6k蛋白表达情况。结果 TRALI大鼠的主要临床表现为呼吸困难及内毒素样等症状,症状出现率TRALI组较对照组明显增加(P<0.05),Rapa组较TRALI组无明显变化(P>0.05)。TRALI组、Rapa组和对照组大鼠肺损伤病理综合评分分别为9.30±2.21 vs 6.60±1.78 vs 2.60±1.82(P<0.01)。TRALI组、Rapa组和对照组大鼠肺组织的磷酸化蛋白p-p70s6k表达的Western blot条带半定量结果分别为0.566 4±0.032 9 vs 0.114 2±0.006 4 vs 0.438 4±0.022 1(P<0.01)。结论 TRALI病程中m TOR信号通路明显活化,应用Rapa可有效抑制m TOR信号通路过度活化状态,并能部分缓解肺组织病理损伤程度。

Objective To investigate the effects of rapamycin on expressions of mTOR signaling pathway down-stream proteins pT0s6k/p-p70s6k and pulmonary histopathological changes in transfusion-related acute lung injury （TRALI） model in SD rats. Methods 30 SD rats were randomly divided into 3 groups （ 10 rats/group）. TRALI group received LPS 2 mg/ kg by intraperitoneal injection and human plasma 5 mL/kg by vein injection. Rapamycin group （ Rapa group） received rapa- mycin 10 mg/kg for consecutively three days by intragastric administration and then TRALI model. The control group re- ceived placebo operation. The main sYmptoms, pulmonary histopathological changes and the expressions of p70s6k/p-p70s6k were evaluated. Results The main sYmptoms between TRALI group and control group showed significant differences （P 〈 0. 05）. However, between TRALI group and Rapa group there were little differences （P 〉 0. 05）. The scores of pulmonary histopathological changes of TRAIl group vs Rapa group vs control group was 9. 30 ± 2.21 vs 6. 60 ± 1.78 vs 2. 60 ± 1.82 （P 〈 0. 01 ）. The band densitometry semi-quantified data of p-p70s6k expressions in TRALI group vs Rapa group vs control group was 0. 566 4 ± 0. 032 9 vs 0. 114 2 ± 0. 006 4 vs 0. 438 4 ± 0. 022 1 （ P 〈 0. 01 ）. Conclusion The mTOR signaling pathway is activated in the process of TRALI. Administration of rapamycin effectively inhibits the over-activation of mTOR signaling pathway in TRALI and ameliorates the severity of pulmonary histopathology.