双侧突发性聋患者血清胆红素与听力损失程度的相关性
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摘要
目的:探讨血清胆红素水平与双侧突发性聋(突聋)听力损失严重程度的相关性。方法:连续纳入113例双侧突聋患者,应用单因素和多因素线性回归模型探究血清胆红素水平与初始听力水平之间的关系。结果:相较于听力损失中度及以下者(≤70dB HL),>70dB HL的双侧突聋患者具有相对较低的血清总胆红素和间接胆红素水平,相对较高的白细胞计数、中性粒细胞、血小板、碱性磷酸酶和较差的最终听阈。在调整了可能的混杂因素后,只有血清间接胆红素水平与双侧突聋患者的初始听力损失呈显著负相关。每1μmol/L血清间接胆红素水平的提升对应着初始听力损失降低1.1dB(95%CI:-2.2,0.0)。结论:在正常或接近正常的范围内,较高的间接胆红素水平与双侧突聋患者较轻的初始听力损失程度显著相关,提示在正常或接近正常范围内的血清胆红素对听觉系统可能有益。
Objective:The aim of this study was to investigate the association between serum bilirubin levels and the severity of bilateral sudden sensorineural hearing loss(BSSHL).Method:A total of 113 patients with bilateral axillary sputum were enrolled,and the relationship between serum bilirubin levels and initial hearing levels was explored using a univariate and multivariate linear regression model.Result:Compared with the group with moderate and below hearing loss(≤70 dB HL),patients with severe profound HL(>70 dB HL)were more likely to have lower levels of total and indirect bilirubin level,magnesium and relative hearing gain,higher levels of final hearing,white blood counts,neutrophil,platelet and alkaline phosphatase.After adjusting for possible confounders,only serum indirect bilirubin levels were significantly negatively correlated with initial hearing loss in patients with bilateral axillary sputum.1μmol/L increase of IBIL was associated with 1.1 dB(95%CI:-2.2,0.0)reduction in initial hearing loss.Conclusion:Within the normal or mildly elevated range,higher levels of IBIL are independently and significantly associated with less severe hearing loss in BSSHL.It suggested a beneficial effect of bilirubin on auditory system.
Objective:The aim of this study was to investigate the association between serum bilirubin levels and the severity of bilateral sudden sensorineural hearing loss(BSSHL).Method:A total of 113 patients with bilateral axillary sputum were enrolled,and the relationship between serum bilirubin levels and initial hearing levels was explored using a univariate and multivariate linear regression model.Result:Compared with the group with moderate and below hearing loss(≤70 dB HL),patients with severe profound HL(>70 dB HL)were more likely to have lower levels of total and indirect bilirubin level,magnesium and relative hearing gain,higher levels of final hearing,white blood counts,neutrophil,platelet and alkaline phosphatase.After adjusting for possible confounders,only serum indirect bilirubin levels were significantly negatively correlated with initial hearing loss in patients with bilateral axillary sputum.1μmol/L increase of IBIL was associated with 1.1 dB(95%CI:-2.2,0.0)reduction in initial hearing loss.Conclusion:Within the normal or mildly elevated range,higher levels of IBIL are independently and significantly associated with less severe hearing loss in BSSHL.It suggested a beneficial effect of bilirubin on auditory system.
引文
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[20]PAE H O,SON Y,KIM N H,et al.Role of heme oxygenase in preserving vascular bioactive NO[J].Nitric Oxide,2010,23:251-257.
[21]KUNDUR A R,SINGH I,BULMER A C.Bilirubin,platelet activation and heart disease:a missing link to cardiovascular protection in Gilbert's syndrome?[J].Atherosclerosis,2015,239:73-84.
[22]QUARANTA N,SQUEO V,SANGINETO M,et al.High Total Cholesterol in Peripheral Blood Correlates with Poorer Hearing Recovery in Idiopathic Sudden Sensorineural Hearing Loss[J].PLoS One,2015,10:e0133300.
[23]RYTER S W,CHOI A M.Heme oxygenase-1:molecular mechanisms of gene expression in oxygen-related stress[J].Antioxid Redox Signal,2002,4:625-632.
[24]ERKAN A,EKICI B,UGURLU M,et al.The role of bilirubin and its protective function against coronary heart disease[J].Herz,2014,39:711-715.
[25]GIRAUDI P J,BELLAROSA C,CODA-ZABETTA CD,et al.Functional induction of the cystine-glutamate exchanger system Xc(-)activity in SH-SY5Ycells by unconjugated bilirubin[J].PLoS One,2011,6:e29078.
[26]FRANCHINI M,TARGHER G,LIPPI G.Serum bilirubin levels and cardiovascular disease risk:a Janus Bifrons?[J].Adv Clin Chem,2010,50:47-63.
[27]YE H B,SHI H B,WANG J,et al.Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage[J].J Neurosci Res,2012,90:2201-2213.
[28]LIN J P,VITEK L,SCHWERTNER H A.Serum bilirubin and genes controlling bilirubin concentrations as biomarkers for cardiovascular disease[J].Clin Chem,2010,56:1535-1543.
[29]VTEK L.The role of bilirubin in diabetes,metabolic syndrome,and cardiovascular diseases[J].Front Pharmacol,2012,3:55-55.
[30]GAZZIN S,VITEK L,WATCHKO J,et al.A Novel Perspective on the Biology of Bilirubin in Health and Disease[J].Trends Mol Med,2016,22:758-768.
[31]VTEK L,SCHWERTNER H A.The heme catabolic pathway and its protective effects on oxidative stressmediated diseases[J].Adv Clin Chem,2007,43:1-57.
[2]JARIENGPRASERT C,LAOTHAMATAS J,JAN-WITYANUJIT T,et al.Bilateral sudden sensorineural hearing loss as a presentation of metastatic adenocarcinoma of unknown primary mimicking cerebellopontine angle tumor on the magnetic resonance image[J].Am J Otolaryngol,2006,27:143-145.
[3]KIM S M,JO J M,BAEK M J.A case of bilateral sudden hearing loss and tinnitus after salicylate intoxication[J].Korean J Audiol,2013,17:23-26.
[4]AGAH E,HABIBI A,NADERI H,et al.Metronidazole-induced neurotoxicity presenting with sudden bilateral hearing loss,encephalopathy,and cerebellar dysfunction[J].Eur J Clin Pharmacol,2017,73:249-250.
[5]LEE H,WHITMAN G T,LIM J G,et al.Bilateral sudden deafness as a prodrome of anterior inferior cerebellar artery infarction[J].Arch Neurol,2001,58:1287-1289.
[6]FETONI A R,MANCUSO C,ERAMO S L,et al.In vivo protective effect of ferulic acid against noise-induced hearing loss in the guinea-pig[J].Neuroscience,2010,169:1575-1588.
[7]FETONI A R,ERAMO S L,PACIELLO F,et al.Curcuma longa(curcumin)decreases in vivo cisplatininduced ototoxicity through heme oxygenase-1induction[J].Otol Neurotol,2014,35:e169-177.
[8]SO H,KIM H,KIM Y,et al.Evidence that cisplatininduced auditory damage is attenuated by downregulation of pro-inflammatory cytokines via Nrf2/HO-1[J].J Assoc Res Otolaryngol,2008,9:290-306.
[9]CHAN K H,NG MK,STOCKER R.Haem oxygenase-1and cardiovascular disease:mechanisms and therapeutic potential[J].Clin Sci,2011,120:493-504.
[10]WAGNER K H,WALLNER M,MOLZER C,et al.Looking to the horizon:the role of bilirubin in the development and prevention of age-related chronic diseases[J].Clin Sci,2015,129:1-25.
[11]AKBOGA M K,CANPOLAT U,SAHINARSLANA,et al.Association of serum total bilirubin level with severity of coronary atherosclerosis is linked to systemic inflammation[J].Atherosclerosis,2015,240:110-114.
[12]STOCKER R.Antioxidant activities of bile pigments[J].Antioxid Redox Signal,2004,6:841-849.
[13]LU Y Y,JIN Z,TONG B S,et al.A clinical study of microcirculatory disturbance in Chinese patients with sudden deafness[J].Acta Otolaryngol,2008,128:1168-1172.
[14]RUDACK C,LANGER C,STOLL W,et al.Vascular risk factors in sudden hearing loss[J].Thromb Haemost,2006,95:454-461.
[15]MOSNIER I,STEPANIAN A,BARON G,et al.Cardiovascular and thromboembolic risk factors in idiopathic sudden sensorineural hearing loss:a case-control study[J].Audiol Neurootol,2011,16:55-66.
[16]LIN R J,KRALL R,WESTERBERG B D,et al.Systematic review and meta-analysis of the risk factors for sudden sensorineural hearing loss in adults[J].Laryngoscope,2012,122:624-635.
[17]AKINPELU O V,WAISSBLUTH S,DANIEL S J.Auditory risk of hyperbilirubinemia in term newborns:a systematic review[J].Int J Pediatr Otorhinolaryngol,2013,77:898-905.
[18]AHLFORS C E,PARKER A E.Unbound bilirubin concentration is associated with abnormal automated auditory brainstem response for jaundiced newborns[J].Pediatrics,2008,121:976-978.
[19]AHLFORS C E,AMIN S B,PARKER A E.Unbound bilirubin predicts abnormal automated auditory brainstem response in a diversenewborn population[J].JPerinatol,2009,29:305-309.
[20]PAE H O,SON Y,KIM N H,et al.Role of heme oxygenase in preserving vascular bioactive NO[J].Nitric Oxide,2010,23:251-257.
[21]KUNDUR A R,SINGH I,BULMER A C.Bilirubin,platelet activation and heart disease:a missing link to cardiovascular protection in Gilbert's syndrome?[J].Atherosclerosis,2015,239:73-84.
[22]QUARANTA N,SQUEO V,SANGINETO M,et al.High Total Cholesterol in Peripheral Blood Correlates with Poorer Hearing Recovery in Idiopathic Sudden Sensorineural Hearing Loss[J].PLoS One,2015,10:e0133300.
[23]RYTER S W,CHOI A M.Heme oxygenase-1:molecular mechanisms of gene expression in oxygen-related stress[J].Antioxid Redox Signal,2002,4:625-632.
[24]ERKAN A,EKICI B,UGURLU M,et al.The role of bilirubin and its protective function against coronary heart disease[J].Herz,2014,39:711-715.
[25]GIRAUDI P J,BELLAROSA C,CODA-ZABETTA CD,et al.Functional induction of the cystine-glutamate exchanger system Xc(-)activity in SH-SY5Ycells by unconjugated bilirubin[J].PLoS One,2011,6:e29078.
[26]FRANCHINI M,TARGHER G,LIPPI G.Serum bilirubin levels and cardiovascular disease risk:a Janus Bifrons?[J].Adv Clin Chem,2010,50:47-63.
[27]YE H B,SHI H B,WANG J,et al.Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage[J].J Neurosci Res,2012,90:2201-2213.
[28]LIN J P,VITEK L,SCHWERTNER H A.Serum bilirubin and genes controlling bilirubin concentrations as biomarkers for cardiovascular disease[J].Clin Chem,2010,56:1535-1543.
[29]VTEK L.The role of bilirubin in diabetes,metabolic syndrome,and cardiovascular diseases[J].Front Pharmacol,2012,3:55-55.
[30]GAZZIN S,VITEK L,WATCHKO J,et al.A Novel Perspective on the Biology of Bilirubin in Health and Disease[J].Trends Mol Med,2016,22:758-768.
[31]VTEK L,SCHWERTNER H A.The heme catabolic pathway and its protective effects on oxidative stressmediated diseases[J].Adv Clin Chem,2007,43:1-57.