GSK-3β抑制剂TDZD-8对大鼠肺缺血再灌注时NF-κB活化的影响  

Effect of GSK-3β inhibitor TDZD-8 on activation of NF-kB during lung ischemia-reperfusion in rats

作　　者：徐晓梅[1] 王子文[1] 王志萍[2] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,221002 [2]南京医科大学附属无锡市人民医院麻醉科

出　　处：《中华麻醉学杂志》2012年第9期1140-1142,共3页Chinese Journal of Anesthesiology

摘　　要：目的评价GSK-3β抑制剂TDZD-8对大鼠肺缺血再灌注时NF-kB活化的影响。方法健康雄性SD大鼠32只，8～10周龄．体重250～280g，采用随机数字表法，将其随机分为4组（n=8）：假手术组（sham组）、肺缺血冉灌注组（I／R组）、肺缺血再灌注＋DMSO组（1／R＋DMSO组）和肺缺血再灌注＋GSK-3β抑制剂TDZD-8组（I／R＋TDZD-8组）。采用夹闭左肺门1h恢复灌注的方法制备肺缺血再灌注模型；I／R＋DMSO组和I／R＋TDZD-8组于再灌注前5min分别于颈外静脉注射10％DMSO和TDZD培1mg／kg。下再灌注2h时取腹主动脉血测定动脉血氧分压（Pa02）、血浆IL-6和TNF-a浓度；然后处死大鼠，取肺组织测定肺湿干重比（W／D）、髓过氧化物酶（MPO）活性及p-GSK-3β以及p-NF-kB p65的表达，电镜下观察肺组织病理学结果。结果与sham组比较，其余3组PaO2和肺组织p-GSK-3β表达水平降低，血浆IL-6和TNF-a浓度，肺组织W／D、MPO活性及p—NF-kBp65表达水平升高（P〈0．05），I／R＋TDZD-8组PaO2和P-GSK-3β表达水平升高，上述其余各指标降低（P〈0．05）。I／R＋DMSO组与I／R组各指标差异无统计学意义（P〉0．05）。I／R＋TDZD-8组肺组织病理学损伤较I／R组减轻。结论GSK-3β抑制剂TDZD-8可通过下调NF-kB磷酸化抑制炎性反应，从而减轻肺缺血再灌注损伤。Objective To investigate the effect of GSK-3β inhibitor TDZD-8 on activation of NF-kB during lung ischemia-repeffusion （I/R） in rats. Methods Thirty-two healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-280 g, were randomly divided into 4 groups （n = 8 each）： sham operation group （sham group） ; I/R group, I/R ＋ dimethyl sulfoxide （DMSO） group and I/R ＋ TDZD-8 group. Lung I/R was induced by clamping the left hilum of lung for 1 h followed by 2 h reperfusion. 10% DMSO and TDZD-8 1 mg/kg were inject- ed intravenously at 5 min before reperfusion in groups I/R ＋ DMSO and I/R ＋ TDZD-8, respectively. Blood sam- ples were taken at 2 h of repeffusion for determination of arterial partial pressure of oxygen （PaO2） and concentra- tions of plasma interleukin-6 （IL-6） and tumor necrosis factor-a （TNF-a） . The animals were then sacrificed and the left lung was removed for determination of W/D lung weight ratio, myeloperpxidase （MPO） activity, expression of phosphorylated glycogen synthase kinase-3 beta （p-GSK-313） and phosphorylated nuclear factor-kappa B p65 （p- NF-kB p65） and for microscopic examination. Results Compared with sham group, PaO2 and the expression of p- GSK-3β were significantly decreased, and the concentrations of plasma IL-6 and TNF-a, W/D lung weight ratio, MPO activity and expression of p-NF-kB p65 were significantly increased in the other groups （P 〈 0.05）, and PaO2 and the expression of p-GSK-3β were significantly increased and the other Parameters were significantly de- creased in I/R ＋ TDZD-8 group （P 〈 0.05）. There were no significant differences in the parameters mentioned above among groups I/Rand I/R ＋ DMSO （ P 〉 0.05）. Microscopic examination showed that I/R-induced lung in- jury was ameliorated by TDZD-8.Conclusion GSK-3β inhibitor TDZD-8 can attenuate lung I/R injury by down- regulating phosphorylation of NF-kB p65 and inhibiting inflammatory response.

关 键 词：蛋白质丝氨酸苏氨酸激酶 再灌注损伤 肺 NF-KB 

分 类 号：R614[医药卫生—麻醉学]