去铁胺对大鼠肺组织低氧诱导因子-1表达及对模拟高原低氧大鼠肺组织结构的影响  

Effects of desferrioxamine on HIF-1α expression in rat lungs and on the pulmonary structure in rats subjected to hypoxia at simulated high altitude

作　　者：李福祥[1] 夏前明[1] 徐朝霞[2] 全燕[1] 李鸿雁[1] 连亨宁 胡绳[1] 张彦[1] 

机构地区：[1]成都军区总医院呼吸科,成都市610083 [2]成都军区总医院急诊科,都市610083

出　　处：《实用医学杂志》2008年第17期2948-2951,共4页The Journal of Practical Medicine

基　　金：中国人民解放军全军医药卫生科研基金(编号:01MB038)

摘　　要：目的:观察去铁胺对大鼠肺组织低氧诱导因子-1(HIF-1α)表达及对模拟高原低氧环境下肺结构的影响。方法:实验分成两部分,(1)25只Wistar大鼠随机分成5组,腹腔注射去铁胺(DFX)200mg/kg后,分别用RT-PCR和免疫组化方法在各个时相点(0、2、4、8、24h)检测肺组织HIF-1α mRNA和蛋白质的表达。(2)40只Wistar大鼠随机分成5组,每组8只。常氧对照组(N),急性低氧对照组(H0),急性低氧组(H1),DFX处理组(DFX0),DFX处理+急性低氧组(DFX1)。各组动物经相应处理后,测定N、H0、DFX0组肺组织HIF-1α mRNA,观察N、H1、DFX1组肺显微及超微结构变化并检测肺组织一氧化氮浓度及Na+-K+-ATP酶活性。结果:(1)大鼠腹腔注射DFX后肺组织未表达HIF-1α蛋白质,对照组(0h)大鼠肺组织少量表达HIF-1α mRNA,2h后开始升高,4h达峰值(P<0.01),以后逐渐下降,24h后基本恢复到正常对照组水平。(2)大鼠腹腔注射DFX200mg/kg,1次/d,5d后,DFX0组HIF-1α mRNA表达水平显著高于H0和N组(P<0.01)。(3)经模拟海拔6000m急性低氧24h后,H1组肺组织NO浓度和Na+-K+-ATP酶活性低于N组(P<0.01),而DFX1较H1组明显升高(P<0.01)。(4)经模拟海拔6000m急性低氧24h后,H1组肺出现明显的间质性水肿,而DFX1组则水肿明显减轻。结论:DFX可以促进大鼠肺组织表达HIF-1α mRNA;间断腹腔注射DFX可以减轻大鼠低氧性肺间质水肿并提升肺组织NO浓度和Na+-K+-ATP酶活性。Objective To study the effects of DFX on HIF-1α expression in the lungs and on the pulmonary structure in rats exposed to simulated hypoxic surroundings. Methods This experiment was divided into two parts： （1） 25 Wistar rats were randomly divided into five groups. The expressions of HIF-1α mRNA and protein in the lungs were detected at 0, 2, 4, 8, and 24 h after an intraperitoneal injection of DFX of 200 mg/kg. （2） Another 40 rats were randomized to five groups, 8 for each group： Normal oxygen control group （N）, acute hypoxia control group （Ho）, acute hypoxia group （H1）, DFX treatment group （DFX0）, DFX treatment and acute hypoxia group （DFX1）. The expression of HIF-1α mRNA in groups N, H0, and DFX0 and NO level and Na^＋ -K^＋ -ATPase activity in groups N, H1, and DFX1 were detected. The pulmonary structure was also observed. Results （1）After an intraperitoneal injection of DFX, no HIF-1α proteins were detected in all groups, while a lower level of HIF-1α mRNA was detectable initially, increased at 2 h, peaked at 4 h （P 〈 0.01）, then decreased gradually and returned to normal at 24 h. （2） 5 days after continuous injections of DFX, the expression level of HIF-1α mRNA was obviously higher in group DFX0 than in groups Ho and N （P 〈 0.01）. （3） After subjected to acute hypoxia at a simulated altitude of 6 000 m for 24 h, NO level and Na^＋ -K^＋ -ATPase activity in group Hi were significantly lower than those in group N （P 〈 0.01 ）, NO level and Na^＋ -K^＋ - ATPase activity were markedly elevated in group DFX1 as compared with group H1 （P 〈 0.01）. （4） After subjected to acute hypoxia at a simulated altitude of 6 000 m for 24 h, obvious pulmonary interstitial edema was found in group H1 and edema was markedly reduced in group DFX1. Conclusions DFX can induce HIF-1α mRNA expression in rat lungs. Intermittent intraperitoneal injections of DFX may relieve the degree of hypoxia-induced pulmonary interstitial edema and elevate NO level and

关 键 词：细胞低氧 代谢 低氧诱导因子 一氧化氮 NA+-K+-ATP酶 

分 类 号：R363[医药卫生—病理学]