Sekine Kazunori, Morita Kyoko, Masuda Kiyoshi, Sato Go, Rokutan Kazuhito, Takeda Noriaki
Department of Otolaryngology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
ORL J Otorhinolaryngol Relat Spec. 2005;67(5):294-9. doi: 10.1159/000089411. Epub 2005 Dec 15.
We developed an original microarray carrying 1,467 cDNAs of stress-related genes for the assessment of stress responses. In this study, we used microarray analysis to assess the stress-related gene expression profiles in peripheral leukocytes in 2 patients with definite Ménière's disease. In the attack and active phases, mRNA expression levels of 57 genes and 163 genes were either up-regulated more than twofold or down-regulated by less than half in patient 1 and patient 2, respectively. Patient 1 had sporadic episodes of vertigo attack, while patient 2 had an intractable course with frequent vertigo attacks, suggesting that the magnitude of changes in gene expression is correlated with the severity of the disorder in Ménière's disease. The expression of a total of 26 genes commonly changed in both patients in the attack and active phases and returned to the baseline levels in the remission phase, suggesting the involvement of the distinct group of stress-related genes in the development of vertigo attacks in Ménière's disease. We then examined the effects of caloric stimulation on the stress-related gene expression profiles in peripheral leukocytes in 5 healthy volunteers. Although unilateral caloric stimulation with cold water caused acute vertigo with nystagmus, the expression profiles of stress-related genes did not significantly change after this experiment. This finding indicated that the up- or down-regulated genes in the attack and active phases in patients with Ménière's disease are not secondary to vertigo or vertigo-associated anxiety. All these findings suggested that the distinct group of stress-related genes contributed to the development of vertigo attacks of Ménière's disease and that stress-related gene expression profiles in peripheral leukocytes can be a predictive and therapeutic tool for episodic vertigo attacks in patients with Ménière's disease.
我们开发了一种携带1467个应激相关基因cDNA的原创性微阵列，用于评估应激反应。在本研究中，我们使用微阵列分析来评估2例确诊梅尼埃病患者外周血白细胞中应激相关基因的表达谱。在发作期和活动期，患者1和患者2中分别有57个基因和163个基因的mRNA表达水平上调超过两倍或下调至不到一半。患者1有散发性眩晕发作，而患者2病程顽固，频繁发作眩晕，这表明基因表达变化的幅度与梅尼埃病病情的严重程度相关。在发作期和活动期，两名患者共有26个基因的表达发生了共同变化，并在缓解期恢复到基线水平，这表明一组独特的应激相关基因参与了梅尼埃病眩晕发作的发生。然后，我们检测了5名健康志愿者的外周血白细胞中热刺激对应激相关基因表达谱的影响。尽管用冷水进行单侧热刺激会导致急性眩晕伴眼球震颤，但该实验后应激相关基因的表达谱没有明显变化。这一发现表明，梅尼埃病患者发作期和活动期上调或下调的基因并非继发于眩晕或与眩晕相关的焦虑。所有这些发现表明，一组独特的应激相关基因促成了梅尼埃病眩晕发作的发生，并且外周血白细胞中应激相关基因的表达谱可以作为梅尼埃病发作性眩晕发作的预测和治疗工具。
