环磷酸腺苷-蛋白激酶A信号通路对大鼠深低温缺血再灌注后肺组织水通道蛋白-5的调控及其与肺损伤的关系  

Regulatory effect of cyclic adenosine monophosphate-protein kinase A signaling pathway on apua- porin 5 expression in a rat model of lung ischemia reperfusion after deep hypothermia and its rela- tion to lung injury

作　　者：吴智勇[1] 王志芹 毛志福[1] 胡锐[1] 戴飞峰[1] 张昊[1] 王志维[1] 

机构地区：[1]武汉大学人民医院心血管外科,430060 [2]武汉市武昌医院妇产科

出　　处：《中华实验外科杂志》2013年第8期1605-1607,共3页Chinese Journal of Experimental Surgery

摘　　要：目的探讨环磷酸腺苷-蛋白激酶A（cAMP-PKA）信号通路对大鼠深低温缺血再灌注后肺组织水通道蛋白-5（AQP5）的调控及其与肺损伤的关系。方法将28只Wistar大鼠随机分为假手术组（sham组）、深低温缺血再灌注损伤组（I／R组）、H89组和forskolin组，每组7只。I／R组大鼠体表降温至深低温后阻断左下肺门30min后开放、复温；sham组只开胸但不降温阻断左下肺门；H89组和forskolin组分别于实验前2d腹腔注射H89和forskolin，其余操作同LZR组；测量左下肺组织湿重／干重比值（W／D比值）同时观察组织学变化，实时定量聚合酶链反应（Real—timePCR）以及Westernblot法检测左下肺组织中AQP5mRNA和蛋白表达。结果I／R组与sham组比较，肺组织AQP5mRNA表达减少（0．67±0．15，P〈0．01）、AQP5蛋白表达减少（0．47±0．09，P〈0．01），W／D比值增高（5．27±0．92，P〈0．01），肺组织形态及结构明显受损；forskolin干预组与I／R组比较，肺组织AQP5mRNA表达增加（0．83±0．30，P〈0．01）、AQP5蛋白表达增加（0．89±0．07，P〈0．01）、W／D比值减低（3．98±0．45，P〈0．01），肺组织病理形态学改变轻于I／R组，与sham组比较，AQP5表达减少，但差异无统计学意义；H89干预组与I／R组和sham组比较，肺组织AQP5mRNA表达减少（0．53±0．11，P〈0．01）、AQP5蛋白表达减少（0．31±0．03，P〈0．01），W／D比值增高（6．13±0．78，P〈0．01），肺组织形态及结构受损最为明显。结论深低温缺血再灌注肺组织中AQP5表达下调且与肺损伤程度相关，cAMP—PKA信号通路可能参与AQP5的调控。Objective To discuss the regulatory effect of cyclic adenosine monophosphate-protein kinase A （cAMP-PKA） signaling pathway on the apuaporin 5 （AQP5） expression in a rat model of lung is- chemia reperfusion after deep hypothermia and its relation to lung injury. Methods Twenty-eight Wistar rats were randomly divided into sham group, ischemia-reperfusion group （I/R group）, H89 group, and Forskoliu group. The left lower hilus pulmonis of I/R group was blocked for 30 min after its body tempera- ture cooled to deep hypothermia and soon opened and rewarmed. The rats in the sham group only undergone thoracotomy without cooling and blocking. The rats in the H89 group and Forskolin group were intraperito- neally injected with H89 and Forskolin 2 days before experiment, respectively. The rest procedures were the same to those in the I/R group. The lung specimens were pathologically observed and wet/dry weight ratio was measured. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot- ting methods were applied to detect the expression of AQP5 in all groups. Results As compared with sham group, the expression of AQP5 mRNA was reduced （0. 67 ±0. 15 ,P 〈0. 01 ）, the expression of AQP5 pro- tein declined （0. 47 ± 0. 09, P 〈 0.01 ）, W/D ratio increased （5. 27 ± 0. 92, P 〈 0. 01 ） , the morphology and structure of lung tissue was significantly impaired in the I/R group. As compared with I/R group, the expression of AQP5 mRNA was increased （ 0. 83 ±0. 30, P 〈 0. 01 ） , the expression of AQP5 protein in-creased （0. 89 ±0.07,P〈0. 01）, W/D ratio was reduced （3, 98 ±0. 45,P〈0. 01 ）, the injury of lung tissue was significantly alleviated in the Forskolin group There was no statistically significant difference be- tween sham group and Forskolin group. As compared with I/R group and sham group, the AQP5 mRNA expression was decreased （0. 53 ± 0. 11, P 〈 0. 01 ）, the AQP5 protein expression decreased （0. 31 ± O, 03 ,P 〈0. 01 ）, W/D ratio incr

关 键 词：深低温 肺缺血 再灌注损伤 水通道蛋白-5 环磷酸腺苷 蛋白激酶A信 号通路 

分 类 号：R363[医药卫生—病理学]