阻塞性睡眠呼吸暂停低通气综合征患者血清HIF-1α、EPO水平与认知的相关性
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摘要
目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者缺氧诱导因子-1α(HIF-1α)、促红细胞生成素(EPO)与认知功能的关系。方法测定60例OSAHS患者及同期20名健康体检者(对照组)血清HIF-1α、EPO水平,并使用老年认知功能减退知情者问卷(IQCODE)对认知功能进行评分,分析血清HIF-1α、EPO水平与认知功能的相关性。结果 (1)OSAHS患者血清HIF-1α、EPO水平高于对照组,其IQCODE总分和远期记忆力、学习能力评分高于对照组,差异有统计学意义(P <0.05);(2)OSAHS组血清HIF-1α、EPO水平与IQCODE总分呈正相关(rHIF-1α=0.49,rEPO=0.58,P <0.001);(3)受试者工作特征曲线分析OSAHS患者认知功能损害HIF-1α、EPO曲线下面积分别为0.81和0.80。结论 HIF-1α和EPO参与OSAHS缺氧应激过程,在一定程度上,其水平与认知功能损害程度存在相关性。
Objective To investigate the correlations of serum hypoxia inducible factor 1α(HIF-1α)and serum Erythropoietin(EPO)levels with cognitive function in patients with obstructive sleep apnea hypopnea syndrome(OSAHS). Methods Sixty patients with OSAHS and twenty controls were recruited. HIF-1α and EPO levels were determined by ELISA. Cognitive function was measured by the Informant Questionnaire on Cognitive Decline in the Elderly(IQCODE). The Correlation between serum HIF-α,EPO levels and cognitive function was analyzed. Results The serum levels of HIF-1α and EPO in the OSAHS patients were significantly higher than those in the healthy control group,and the total score of IQCODE and the score of long-term memory were significantly higher than those of the control group(P < 0.05). HIF-1α level and EPO level in the OSAHS patients were positive correlated with the total score of IQCODE(rHIF-1α = 0.49,rEPO = 0.58,P < 0.001. Regarding cognitive dysfunction in the OSAHS patients,the areas under ROC curve of HIF-1α and EPO were 0.81 and 0.80. Conclusions HIF-1α and EPO may play an important role in hypoxia condition in the OSAHS patients. To a certain extent,the level of HIF-1α and EPO are correlated with the degree of cognitive impairment.
Objective To investigate the correlations of serum hypoxia inducible factor 1α(HIF-1α)and serum Erythropoietin(EPO)levels with cognitive function in patients with obstructive sleep apnea hypopnea syndrome(OSAHS). Methods Sixty patients with OSAHS and twenty controls were recruited. HIF-1α and EPO levels were determined by ELISA. Cognitive function was measured by the Informant Questionnaire on Cognitive Decline in the Elderly(IQCODE). The Correlation between serum HIF-α,EPO levels and cognitive function was analyzed. Results The serum levels of HIF-1α and EPO in the OSAHS patients were significantly higher than those in the healthy control group,and the total score of IQCODE and the score of long-term memory were significantly higher than those of the control group(P < 0.05). HIF-1α level and EPO level in the OSAHS patients were positive correlated with the total score of IQCODE(rHIF-1α = 0.49,rEPO = 0.58,P < 0.001. Regarding cognitive dysfunction in the OSAHS patients,the areas under ROC curve of HIF-1α and EPO were 0.81 and 0.80. Conclusions HIF-1α and EPO may play an important role in hypoxia condition in the OSAHS patients. To a certain extent,the level of HIF-1α and EPO are correlated with the degree of cognitive impairment.
引文
[1]WU L Y,DING A S,ZHAO T,et al.Involvement of increased stability of mitochondrial membrane potential and overexpression of Bcl-2 in enhanced anoxic tolerance induced by hypoxic preconditioning in cultured hypothalamic neurons[J].Brain Res,2004,999(2):149-154.
[2]CAI Z,SEMENZA G L.Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury[J].Circulation,2004,109(17):2050-2053.
[3]XI L,TAHER M,YIN C,et al.Cobalt chloride induces delayed cardiac preconditioning in mice through selective activation of HIF-1alpha and AP-1 and i NOS signaling[J].Am J Physiol Heart Circ Physiol,2004,287(6):2369-2375.
[4]WANG X,DENG J,BOYLE D W,et al.Potential role of IGF-Iin hypoxia tolerance using a rat hypoxic-ischemic model:activation of hypoxia-inducible factor 1alpha[J].Pediatr Res,2004,55(3):385-394.
[5]KANG M J,JUNG S M,KIM M J,et al.DNA-dependent protein kinase is involved in heat shock protein-mediated accumulation of hypoxia-inducible factor-1alpha in hypoxic preconditioned Hep G2 cells[J].FEBS J,2008,275(23):5969-5981.
[6]ITURRI P,BAIRAM A,SOLIZ J.Efficient breathing at neonatal ages:A sex and Epo-dependent issue[J].Respir Physiol Neurobiol,2017,245:89-97.
[7]CAI Z,MANALO D J,WEI G,et al.Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury[J].Circulation,2003,108(1):79-85.
[8]FLETCHER L,KOHLI S,SPRAGUE S M,et al.Intranasal delivery of erythropoietin plus insulin-like growth factor-I for acute neuroprotection in stroke[J].J Neurosurg,2009,111(1):164-170.
[9]YUEN C M,LEU S,LEE F Y,et al.Erythropoietin markedly attenuates brain infarct size and improves neurological function in the rat[J].J Investig Med,2010,58(7):893-904.
[10]DANG S,LIU X,FU P,et al.Neuroprotection by local intra-arterial infusion of erythropoietin after focal cerebral ischemia in rats[J].Neurol Res,2011,33(5):520-528.
[11]杨彦玲,朱文侠,陈雅慧,等.促红细胞生成素对脑缺血/再灌注损伤的保护作用[J].中国应用生理学杂志,2010(2):152-153.
[12]ZHU T,ZHAN L,LIANG D,et al.Hypoxia-inducible factor1alpha mediates neuroprotection of hypoxic postconditioning against global cerebral ischemia[J].J Neuropathol Exp Neurol,2014,73(10):975-986.
[13]QIAO Y,LIU Z,YAN X,et al.Effect of intermittent hypoxia on neuro-functional recovery post brain ischemia in mice[J].J Mol Neurosci,2015,55(4):923-930.
[14]ZHANG Y,WANG L,DEY S,et al.Erythropoietin action in stress response,tissue maintenance and metabolism[J].Int JMol Sci,2014,15(6):10296-10333.
[15]WITTHUHN B A,QUELLE F W,SILVENNOINEN O,et al.JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin[J].Cell,1993,74(2):227-236.
[16]PRASS K,SCHARFF A,RUSCHER K,et al.Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin[J].Stroke,2003,34(8):1981-1986.
[17]HEYMAN S N,ROSEN S,ROSENBERGER C.Hypoxia-inducible factors and the prevention of acute organ injury[J].Crit Care,2011,15(2):209.
[18]杨清洁,郭军红.探讨重组人促红细胞生成素改善血管性痴呆大鼠认知功能的可能机制[J].中西医结合心脑血管病杂志,2015(17):1940-1943.
[19]RONDON E,VENKATARAMAN R.Afelimomab led to a modest mortality benefit in patients with severe sepsis and elevated interleukin-6 levels[J].Crit Care,2005,9(5):20.
[20]HASHEMI V,FARROKHI A S,TANOMAND A,et al.Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and disease activity in patients with rheumatoid arthritis in Iranian population[J].Immunol Lett,2018,204:16-22.
[2]CAI Z,SEMENZA G L.Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury[J].Circulation,2004,109(17):2050-2053.
[3]XI L,TAHER M,YIN C,et al.Cobalt chloride induces delayed cardiac preconditioning in mice through selective activation of HIF-1alpha and AP-1 and i NOS signaling[J].Am J Physiol Heart Circ Physiol,2004,287(6):2369-2375.
[4]WANG X,DENG J,BOYLE D W,et al.Potential role of IGF-Iin hypoxia tolerance using a rat hypoxic-ischemic model:activation of hypoxia-inducible factor 1alpha[J].Pediatr Res,2004,55(3):385-394.
[5]KANG M J,JUNG S M,KIM M J,et al.DNA-dependent protein kinase is involved in heat shock protein-mediated accumulation of hypoxia-inducible factor-1alpha in hypoxic preconditioned Hep G2 cells[J].FEBS J,2008,275(23):5969-5981.
[6]ITURRI P,BAIRAM A,SOLIZ J.Efficient breathing at neonatal ages:A sex and Epo-dependent issue[J].Respir Physiol Neurobiol,2017,245:89-97.
[7]CAI Z,MANALO D J,WEI G,et al.Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury[J].Circulation,2003,108(1):79-85.
[8]FLETCHER L,KOHLI S,SPRAGUE S M,et al.Intranasal delivery of erythropoietin plus insulin-like growth factor-I for acute neuroprotection in stroke[J].J Neurosurg,2009,111(1):164-170.
[9]YUEN C M,LEU S,LEE F Y,et al.Erythropoietin markedly attenuates brain infarct size and improves neurological function in the rat[J].J Investig Med,2010,58(7):893-904.
[10]DANG S,LIU X,FU P,et al.Neuroprotection by local intra-arterial infusion of erythropoietin after focal cerebral ischemia in rats[J].Neurol Res,2011,33(5):520-528.
[11]杨彦玲,朱文侠,陈雅慧,等.促红细胞生成素对脑缺血/再灌注损伤的保护作用[J].中国应用生理学杂志,2010(2):152-153.
[12]ZHU T,ZHAN L,LIANG D,et al.Hypoxia-inducible factor1alpha mediates neuroprotection of hypoxic postconditioning against global cerebral ischemia[J].J Neuropathol Exp Neurol,2014,73(10):975-986.
[13]QIAO Y,LIU Z,YAN X,et al.Effect of intermittent hypoxia on neuro-functional recovery post brain ischemia in mice[J].J Mol Neurosci,2015,55(4):923-930.
[14]ZHANG Y,WANG L,DEY S,et al.Erythropoietin action in stress response,tissue maintenance and metabolism[J].Int JMol Sci,2014,15(6):10296-10333.
[15]WITTHUHN B A,QUELLE F W,SILVENNOINEN O,et al.JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin[J].Cell,1993,74(2):227-236.
[16]PRASS K,SCHARFF A,RUSCHER K,et al.Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin[J].Stroke,2003,34(8):1981-1986.
[17]HEYMAN S N,ROSEN S,ROSENBERGER C.Hypoxia-inducible factors and the prevention of acute organ injury[J].Crit Care,2011,15(2):209.
[18]杨清洁,郭军红.探讨重组人促红细胞生成素改善血管性痴呆大鼠认知功能的可能机制[J].中西医结合心脑血管病杂志,2015(17):1940-1943.
[19]RONDON E,VENKATARAMAN R.Afelimomab led to a modest mortality benefit in patients with severe sepsis and elevated interleukin-6 levels[J].Crit Care,2005,9(5):20.
[20]HASHEMI V,FARROKHI A S,TANOMAND A,et al.Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and disease activity in patients with rheumatoid arthritis in Iranian population[J].Immunol Lett,2018,204:16-22.