阻塞性睡眠呼吸暂停低通气综合征患者缺氧激活通路的研究

The activated pathways by hypoxia in patients with Obstructive sleep apnea hypopnea syndrome

目的:探讨核因子-κB(NF-κB)与缺氧诱导因子-1(HIF-1)在阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的激活情况。方法 :研究对象分为轻中度OSAHS组(16例)、重度OSAHS组(14例)及对照组(30例),通过实时荧光定量PCR法(Real-time)及Western blotting法分别测定外周血单个核细胞(PBMC)的NF-κB、HIF-1m RNA水平和NF-κB、HIF-1蛋白水平。结果:重度OSAHS组NF-κBp65m RNA及NF-κBp65蛋白表达、HIF-1αm RNA及HIF-1α蛋白表达均显著高于对照组及轻中度OSAHS组(均P<0.01);NF-κBp65 m RNA及NF-κBp65蛋白表达轻中度OSAHS组与对照组无明显差异(P值分别为0.068及0.254),轻中度OSAHS组HIF-1αm RNA明显高于对照组(P<0.05)但HIF-1α蛋白表达无明显差异(P=0.777)。NF-κBp65m RNA及HIF-1αm RNA的表达与呼吸暂停低通气指数(AHI)呈正相关(r=0.493,P=0.006,r=0.508,P=0.004),与夜间最低血氧饱和度(LSa O2)呈负相关(r=-0.488,P=0.006,r=-0.46,P=0.011)。NF-κBp65蛋白表达与AHI呈正相关(r=0.669,P<0.001)。HIF-1α蛋白表达与AHI、氧减指数(ODI)呈正相关(r=0.645,P=0.001;r=0.480,P=0.018)。NF-κBp65m RNA与HIF-1αm RNA呈正相关(r=0.543,P=0.002),NF-κBp65、HIF-1α蛋白表达呈正相关(r=0.716,P<0.001)。结论:OSAHS患者NF-κB及HIF-1的基因和蛋白表达均出现上调,且患者病情越重上调越明显,表明OSAHS的发病与两者均有关。

Objective To investigate the activation of nuclear factor-B （NF-B）and hypoxia-inducible factor-1 （HIF-1）in patients with obstructive sleep apnea-hypopnea syndrome （OSAHS）. Methods Subjects were classified into mild-to-moderate OSHAS group （n = 16）, severe OSAHS group （n = 14） and the matched control group （n = 30）. Gene and protein expressions of NF-B and HIF-1 were measured by RT-PCR, Western blot in peripheral blood mononuclear cells （PBMC）. Results NF-kB p65 mRNA and NF-KB p65 protein,HIF-lct mRNA and HIF-lct protein in PBMC were significantly higher in severe OSAHS group than those in mild - to-moderate group and control group （P 〈 0.01）. But there were no significant difference in NF-KB p65 mRNA and NF-KB p65 protein between mild-to-moderate group and control group （P = 0.068, P = 0.254 respectively）. Only gene （P 〈 0.05） not the protein （P = 0.777） of HIF-1α was higher in mild-to-moderate as compared with control group. Both NF-kB p65 mRNA and HIF-1α mRNA were positively correlated with AHI （r = 0.493, P = 0.006, r = 0.508, P = 0.004）, while negatively correlated with nighttime lowest blood oxygen saturation （LSaO2）（r = -0.488, P = 0.006, r = -0.46, P = 0.011 ）. There was a positive correlation between NF-kB p65 protein level and AHI （r = 0.669, P 〈 0.001 ）. HIF-1α protein level was positively correlated with AHI, ODI （r = 0.628, P= 0.001 ; r = 0.480, P = 0.018）. There were positive correlations between NF-kBp65mRNA and HIF-1αmRNA （r = 0.543, P = 0.002）, NF-kBp65 and HIF- 1α protein respectively （r = 0.716, P 〈 0.001）. Conclusions As the gene and protein of NF-kB and HIF-1 were up-regulated in patients with OSAHS, and also positively correlated with the severity of sickness. We conclude that both NF-kB and HIF-1 were involed in the pathogenesis of OSAHS.