丝裂原活化蛋白激酶信号对高氧性肺损伤水通道蛋白5的调控机制

发布时间：2018-10-23 08:58

【摘要】：目的:探讨丝裂原活化蛋白激酶(mitogen activated protein kinases,MAPKs)信号通路三亚族ERK、p38、JNK对高氧性肺损伤异常表达水通道蛋白5(aquaporin 5,AQP5)的分子调控机制。方法:制备高氧肺损伤动物模型,通过不同信号途径抑制剂干预。随机将Wistar实验大鼠分为8组(n=6):空气对照组(A)、高氧组(H)、高氧+ERK抑制剂PD98059组(H+PD)、高氧+p38抑制剂SB203580组(H+SB)、高氧+JNK抑制剂SP600125组(H+SP)及空气+抑制剂对照组(A+PD、A+SB、A+SP),采用蛋白质免疫印迹法检测AQP5蛋白表达,real-time PCR检测AQP5 mRNA。结果:Western blot结果显示:A组AQP5蛋白呈较高表达,H组AQP5表达减弱(P=0.000),而H+SB、H+SP组较H组AQP5蛋白表达明显升高(P=0.000),二者中尤以H+SB组其蛋白上调更明显,H+PD组与H组比较无统计学性差异(P=0.737);real-time PCR结果显示:H组AQP5 mRNA表达较空气对照组降低(P=0.000),H+SB、H+SP与H组比较AQP5 mRNA表达升高(P=0.000),二者中尤以H+SB组其mRNA上调更明显,但二者与A组比较,差异仍有统计学意义(P=0.000),而H+PD干预组与H组比较,未见肺组织AQP5 mRNA表达的明显变化(P=0.796)。A组与A+抑制剂对照组(A+PD、A+SB、A+SP)在AQP5蛋白及mRNA表达上均无明显差异。结论:抑制剂SB203580及SP600125在高氧暴露后能增加AQP5蛋白和mRNA表达,因而推测MAPKs通路中p38、JNK可能参与了调控高氧肺损伤AQP5基因表达的下调过程。
[Abstract]:Aim: to investigate the molecular regulatory mechanism of mitogen-activated protein kinase (mitogen activated protein kinases,MAPKs) signaling pathway Sanya ERK,p38,JNK on abnormal expression of aquaporin-5 (aquaporin 5) in hyperoxia induced lung injury. Methods: the animal model of hyperoxia lung injury was established and treated with different signal pathway inhibitors. Wistar rats were randomly divided into 8 groups: air control group, (A), hyperoxia group, (H), hyperoxia ERK inhibitor PD98059 group, (H PD), hyperoxia p38 inhibitor SB203580 group, (H SB), hyperoxia JNK inhibitor SP600125 group, (H SP) and A PD,A SB,A SP), control group, respectively. Expression of AQP5 protein was detected by Western blot and AQP5 mRNA. was detected by real-time PCR. Results: Western blot showed that the expression of AQP5 protein in group A was higher than that in group H (P0. 000), but the expression of AQP5 in group H SB,H SP was significantly higher than that in group H (P0. 000). The up-regulation of AQP5 protein in group H SB was more obvious than that in group H (P 0. 000). The results of real-time PCR showed that the expression of AQP5 mRNA in H group was lower than that in air control group (P0. 000), H SB,H SP was higher than that in H group (P0. 000), especially in H SB group. However, there was still a significant difference between the two groups (P < 0. 000), but there was no significant change of AQP5 mRNA expression in lung tissue in H PD intervention group and H group (P < 0. 796). A group and A PD,A SB,A SP group). There was no significant difference in AQP5 protein and mRNA expression between Pn0. 796). A group and A inhibitor control group (A PD,A SB,A SP). Conclusion: inhibitor SB203580 and SP600125 can increase the expression of AQP5 protein and mRNA after hyperoxia exposure. It is suggested that p38 JNK may be involved in the down-regulation of AQP5 gene expression in hyperoxia-induced lung injury.
【作者单位】：重庆医科大学附属儿童医院急诊科;重庆医科大学附属儿童医院PICU;儿童发育疾病研究省部共建教育部重点实验室、重庆市儿童发育重大疾病诊治与预防国际科技合作基地、儿科学重庆市重点实验室;
【基金】：中华儿科杂志百利儿科科研基金资助项目重庆医科大学校级课题资助项目
【分类号】：R563.8

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