【摘要】：目的：阻塞性睡眠呼吸暫停低通氣綜合征（obstructive sleepapnea-hypopnea syndrome，OSAHS）與感音神經(jīng)性聾是耳鼻咽喉科常見疾病。近年來，研究表明OSAHS患者感音神經(jīng)性聾的發(fā)病率較正常人群高，但機(jī)制尚未明確，目前臨床上對于聽力的檢測雖然可以對患者聽力狀況作出評價(jià)，但其不能提早發(fā)現(xiàn)聽皮層區(qū)神經(jīng)細(xì)胞代謝障礙。現(xiàn)在研究表明，感音神經(jīng)性聾患者的聽皮層區(qū)神經(jīng)代謝產(chǎn)物的變化可能提示其早期的聽力下降，但是目前聽皮層早期代謝變化尚缺乏有效的檢測手段。磁共振波譜分析（proton magnetic resonace spectroscopy，MRS）1973年首次在醫(yī)學(xué)領(lǐng)域應(yīng)用，MRS可以選擇性地、無創(chuàng)地定對活體組織內(nèi)的代謝物濃度進(jìn)行準(zhǔn)確測定，而且他的檢測靈敏度較高，坐標(biāo)中的不同共頻率波峰被其用來分析并且判斷特定化學(xué)物質(zhì)的含量，從而為臨床上測定腦內(nèi)神經(jīng)性病變及腦部良惡性腫瘤等提供參考信息。目前有些原子核，例如：31P、1H、23NA、13C、19F等被用在醫(yī)學(xué)領(lǐng)域進(jìn)行波譜學(xué)研究，在原子核中，氫質(zhì)子在有機(jī)物機(jī)構(gòu)中具有高自然豐度和核磁感性，所以在磁共振波譜研究中氫質(zhì)子是應(yīng)用最多的原子核。體內(nèi)的多種微量代謝物，如N-乙酰門冬氨酸（NAA）、膽堿（Cho）、肌酸（Cr）、乳酸（Lac）、肌醇（mI）、谷氨酸（Glu）和谷氨酰胺（Gln）等可以被氫質(zhì)子磁共振波譜（1H-proton magnetic resonacespectroscopy，1H-MRS）檢測到。本實(shí)驗(yàn)利用磁共振氫質(zhì)子波譜（1H-MRS）檢測不同程度OSAHS患者顳橫回聽皮層區(qū)的早期神經(jīng)代謝產(chǎn)物變化情況，進(jìn)而有效判斷OSAHS患者感音神經(jīng)性聾聽皮層神經(jīng)細(xì)胞早期病變，為尋找可靠早期預(yù)警指標(biāo)提供臨床實(shí)驗(yàn)依據(jù)。 方法：隨機(jī)抽取經(jīng)PSG監(jiān)測確診的OSAHS患者112例以及健康志愿者15例，并對所有患者及健康志愿者進(jìn)行純音測聽及聽性腦干反應(yīng)分析（ABR），純音聽閾篩查將其分為輕中度OSAHS雙側(cè)耳聾組，重度OSAHS雙側(cè)耳聾組，輕中度OSAHS單側(cè)耳聾組，重度OSAHS單側(cè)耳聾組，輕中度OSAHS組，重度OSAHS組以及正常對照組，對各組行雙側(cè)顳橫回聽皮層行1H-MRS檢測，根據(jù)神經(jīng)代謝產(chǎn)物其峰下面積計(jì)算NAA/Cr、Cho/Cr、mI/Cr、NAA/Cho，比較上述各組間差異；測定OSAHS患者呼吸紊亂指數(shù)（Apnea Hyponea Index, AHI）與各神經(jīng)代謝產(chǎn)物NAA/Cr、Cho/Cr、NAA/Cho之間的相關(guān)性，最后ROC曲線用于測定上述各組指標(biāo)診斷早期感音神經(jīng)性聾的靈敏度及特異度，以確定OSAHS患者并發(fā)感音神經(jīng)性聾的神經(jīng)代謝產(chǎn)物的判定閾值。 結(jié)果： 1OSAHS患者中耳聾的發(fā)生率顯著高于正常健康人群，根據(jù)純音測聽結(jié)果分析OSAHS患者組的感音神經(jīng)性聾發(fā)病率為47.4%，OSAHS組的發(fā)病率明顯高于普通人群。 2OSAHS患者AHI指數(shù)與NAA/Cr、Cho/Cr、mI/Cr、NAA/Cho做線性相關(guān)分析，發(fā)現(xiàn)AHI與NAA/Cr、NAA/Cho呈負(fù)相關(guān)性，而與Cho/Cr呈正相關(guān)性。 3正常組左右耳與單純輕中度OSAHS組及重度OSAHS組之間左右耳對應(yīng)聽皮層區(qū)神經(jīng)代謝產(chǎn)物NAA/Cho，三者依次遞減，差異具有統(tǒng)計(jì)學(xué)意義（P0.05）。mI/Cr、Cho/Cr三組依次遞增，輕中度組與重度組分別與正常對照組有統(tǒng)計(jì)學(xué)意義，但兩者差異無統(tǒng)計(jì)學(xué)意義（P0.05）。 4OSAHS伴耳聾組與OSAHS無耳聾組，正常對照組腦內(nèi)神經(jīng)代謝產(chǎn)物之間的比較NAA/Cr、NAA/Cho依次升高，而Cho/Cr、mI/Cr依次降低；OSAHS無耳聾組、輕中度OSAHS伴耳聾組及重度OSAHS伴耳聾組比較，NAA/Cr、NAA/Cho依次遞減，而Cho/Cr、mI/Cr依次遞增，NAA/Cho比較具有差異性（P0.05）。 5單側(cè)神經(jīng)性耳聾組患側(cè)，健側(cè)與正常對照組比較，NAA/Cr、NAA/Cho依次升高，Cho/Cr、mI/Cr依次降低，并具有統(tǒng)計(jì)學(xué)差異（P0.05）。 6采用ROC曲線測定單純OSAHS與OSAHS合并感音神經(jīng)性聾的神經(jīng)代謝產(chǎn)物的判定值（預(yù)警值）。 本研究發(fā)現(xiàn)在NAA與Cho兩者比值在1.93處時(shí)，ROC曲線下面積為73%，其診斷的靈敏度為92%，特異度為78%，靈敏度與特異度均很高，表明當(dāng)NAA/Cho低于1.93時(shí)OSAHS患者可能會(huì)并發(fā)神經(jīng)性耳聾，，其可以作為篩查OSHAS耳聾發(fā)生的一個(gè)特異性指標(biāo)，Cho/Cr及NAA/Cr其曲線下面積為50%，診斷準(zhǔn)確性不高，所以不予考慮。 結(jié)論： 1OSAHS人群中感音神經(jīng)性聾較正常人群中有較高的發(fā)生率。 2本研究發(fā)現(xiàn)OSAHS不伴感音神經(jīng)性聾患者顳橫回神經(jīng)細(xì)胞出現(xiàn)了早期聽皮層神經(jīng)細(xì)胞代謝功能減退征象，與之相比伴有神經(jīng)性耳聾的患者其減退更為明顯。 3結(jié)合神經(jīng)代謝產(chǎn)物變化及ROC測定，初步研究結(jié)果顯示NAA/Cho有可能作為判定該人群感音神經(jīng)性聾發(fā)生的早期判定指標(biāo)。
[Abstract]:Objective: obstructive sleep apnea hypopnea syndrome (obstructive sleepapnea-hypopnea syndrome, OSAHS) and sensorineural hearing loss are common diseases in otolaryngology. In recent years, studies have shown that the incidence of sensorineural deafness in OSAHS patients is higher than that of normal people, but the mechanism is not yet clear, and it is now clinically detected for hearing. It is possible to evaluate the hearing status of the patients, but it is not possible to detect the metabolic disorders in the auditory cortex early. The present study shows that the changes in the nerve metabolites in the auditory cortex area of the patients with sensorineural hearing loss may indicate the early hearing loss, but the early metabolic changes in the auditory cortex are still lacking effective detection methods. Proton magnetic resonace spectroscopy (MRS) was first used in the medical field for the first time in 1973. MRS can selectively and accurately determine the concentration of metabolites in living tissues, and his detection sensitivity is high, and the different common frequency peaks in the coordinates are used to analyze and judge specific chemicals. There are some nuclei, such as 31P, 1H, 23NA, 13C, 19F, etc., which are used in the field of spectroscopy in the field of medicine. In the nucleus, hydrogen protons have high natural abundance and nuclear magnetic susceptibility in organic bodies. Hydrogen protons are the most used nuclei in the spectroscopic study. A variety of trace metabolites in the body, such as N- acetyl aspartic acid (NAA), choline (Cho), creatine (Cr), lactic acid (Lac), inositol (mI), glutamic acid (Glu) and glutamine (Gln), can be detected by the hydrogen proton magnetic resonance spectroscopy (1H-proton magnetic resonacespectroscopy, 1H-MRS). Magnetic resonance hydrogen proton spectroscopy (1H-MRS) was used to detect the changes of early nerve metabolites in the auditory cortex of different levels of OSAHS patients, and then the early pathological changes of the auditory cortex of the sensorineural hearing cortex in OSAHS patients were effectively judged, and the clinical experimental basis was provided for finding reliable early warning indicators.
Methods: 112 OSAHS patients and 15 healthy volunteers were randomly selected by PSG monitoring, and all the patients and healthy volunteers were treated with pure tone audiometry and auditory brainstem response analysis (ABR). The pure tone hearing threshold screening was divided into mild and moderate OSAHS bilateral deafness group, severe OSAHS bilateral deafness group, mild to moderate OSAHS unilateral deafness group and severe OSA. HS unilateral deafness group, mild and moderate OSAHS group, severe OSAHS group and normal control group, 1H-MRS detection was performed on bilateral temporal lateral auditory cortex in each group. According to the area under the peak of nerve metabolism, NAA/Cr, Cho/Cr, mI/Cr, NAA/Cho were calculated and the differences between the groups were compared, and the respiratory disorder index of OSAHS patients (Apnea Hyponea Index,) and the various gods were measured. The correlation between the metabolites NAA/Cr, Cho/Cr, and NAA/Cho, and the final ROC curve was used to determine the sensitivity and specificity of the early diagnosis of sensorineural deafness to determine the threshold of the nerve metabolites in OSAHS patients with sensorineural deafness.
Result:
The incidence of deafness in 1OSAHS patients was significantly higher than that in normal healthy people. According to the results of pure tone audiometry, the incidence of sensorineural hearing loss in OSAHS patients was 47.4%, and the incidence of group OSAHS was significantly higher than that of the general population.
AHI index of patients with 2OSAHS was negatively correlated with NAA/Cr, Cho/Cr, mI/Cr, NAA/Cho, but positively correlated with Cho/Cr.
3 the left and right ears of the normal group and the mild and moderate OSAHS group and the severe OSAHS group corresponded to the nerve metabolites NAA/Cho in the auditory cortex area, and the three decreased in turn. The difference was statistically significant (P0.05).MI/Cr, the Cho/Cr three groups were increasing in turn. The difference between the mild and moderate group and the severe group was statistically significant, but there was no statistical difference between the two groups. Learning meaning (P0.05).
4OSAHS with the deafness group and the OSAHS non deafness group, the comparison of the brain nerve metabolites in the normal control group was NAA/Cr, the NAA/Cho increased in turn, while Cho/Cr and mI/Cr decreased in turn, and the OSAHS without deafness group, the mild and moderate OSAHS accompanied by the deafness group and the severe OSAHS accompanied deafness group, NAA/Cr, NAA/Cho descended in turn. There is a difference (P0.05).
5 Compared with the normal control group, the NAA/Cr and NAA/Cho of the unilateral nervous deafness group increased in turn, Cho/Cr and mI/Cr decreased in turn, and the difference was statistically significant (P 0.05).
6 the ROC curve was used to determine the diagnostic value of the neurometabolites of OSAHS and OSAHS combined with sensorineural hearing loss (early warning value).
This study found that when the ratio of NAA to Cho was 1.93, the area under the ROC curve was 73%, the sensitivity of the diagnosis was 92%, the specificity was 78%, and the sensitivity and specificity were high. It showed that when NAA/Cho was lower than 1.93, OSAHS patients may be accompanied by neurogenic deafness, which could be used as a specific index for screening OSHAS deafness, Cho/Cr and NAA. /Cr the area under the curve is 50%, and the diagnostic accuracy is not high, so it is not considered.
Conclusion:
The incidence of sensorineural hearing loss in the 1OSAHS population was higher than that in the normal population.
2 we found that the temporal transverse gyrus of OSAHS without sensorineural hearing loss appeared in the early auditory cortex of the auditory cortex, and the hypogonadism of the patients with neurogenic deafness was more obvious than that in the patients with neurogenic deafness.
3 combined with the changes of nerve metabolites and the determination of ROC, preliminary findings suggest that NAA/Cho may be an early determinant of the occurrence of sensorineural deafness in this population.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R766

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