NF-κB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表达的影响

目的:探讨大鼠深低温缺血再灌注后肺组织水通道蛋白5(AQP5)的变化及核因子kappa B(NF-κB)信号通路对大鼠肺组织AQP5表达的影响。方法:30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)、PDTC干预组(I/R+PDTC组)。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;PDTC组于实验前2d腹腔注射PDTC,其余操作同I/R组;各组于再灌注复温后1h或相应时间段取肺组织行病理学观察、测肺湿/干重(W/D)比值,实时PCR及Western-blot检测肺组织中AQP5及NF-κB p65的表达。结果:I/R组与Sham组比较肺组织NF-κB p65表达增多(P<0.01),AQP5表达减少(P<0.01)、W/D比值增高(P<0.01),肺组织形态及结构明显受损;PDTC干预组与I/R组比较肺组织NF-κB p65表达减少(P<0.01),AQP5表达增加(P<0.01)、W/D比值减低(P<0.01),肺组织病理形态学改变轻于I/R组,与Sham组比较NF-κB p65表达增多(P<0.01),AQP5表达减少,W/D比值增高(P<0.01)。结论:NF-κB p65表达增加和AQP-5表达下降可能与深低温缺血再灌注造成的急性肺损伤有关,NF-κB信号通路可能负向调控AQP-5的表达。

Role of NF-Kappa B Signal Pathway in the Expression of AQP5 During Lung Ischemia Reperfusion Injury Under Deep Hypothermia in Rats

Objective:To study the expression of Aquaporin 5(AQP5)during lung ischemic reperfusion injury after deep hypothermia in rats and the regulatory effects of NF-κB signal pathway. Methods:Thirty Wistar rats were randomly divided into sham operation group(sham group),ischemia reperfusion after deep hypothermia group(I/R group),and PDTC intervention group(I/ R + PDTC group).The left lower hilus pulmonis of rats in I/R group were blocked for 30min after body temperature cooled to deep hypothermia and soon opened and rewarmed.Rats in sham group only underwent thoracotomy without cooling down and blocking.PDTC were injected intraperitoneally 2days before the experiment in rats of PDTC group while other manipulation was the same to I/R group.The lung specimens were harvested after rewarming for 1hfor pathological analysis,and the wet/dry(W/D)weight ratio were also measured.Real-time PCR and Western-blot were conducted to detect the expression of AQP5and NF-κB p65.Results:Compared with sham group,the expression of AQP5in I/R group reduced(P<0.01)and expression of NF-κB p65increased(P<0.01),and W/D ratio increased(P<0.01),and the structure of lung tissue was seriously impaired;compared with I/R group,the expression of AQP5in PDTC group increased(P<0.01)and expression of NF-κB p65reduced(P<0.01),W/D ratio reduced(P< 0.01),and the destruction of lung tissue was more severe.Compared with sham group,expression of AQP5in PDTC group decreased,while expression of NF-κB p65increased(P<0.01), and W/D ratio increased(P<0.01).Conclusion:The increased expression of AQP5and reduction of NF-κB p65may correlated with acute lung injury caused by deep hypothermic ischemia reperfusion,and it suggests NF-κB signal pathway might be involved in the regulation of AQP5.