Clock gene dysfunction in patients with obstructive sleep apnea syndrome

阻塞性睡眠呼吸暂停综合征患者的时钟基因功能障碍

• 批准号: 17590791
• 负责人: BURIOKA Naoto
• 金额: $ 1.02万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590791/
• 关键词: Physiology; Internal medicine; gene; circadian rhythm; clock gene; sleep apnea syndrome

Clock genes regulate mammalian circadian rhythms, and dysfunction of clock genes can contribute to various disorders. To investigate whether obstructive sleep apnea syndrome (OSAS) influences clock gene function, we examined Period1 (Per1) mRNA expression in vitro and in vivo. In 8 healthy subjects and 8 OSAS patients, we measured plasma noradrenaline, serum IL-6, and high-sensitivity CRP (hs-CRP), and Per1 mRNA expression in peripheral whole blood. Expression of Per1 mRNA in cultured cells was examined under IL-6 or noradrenaline stimulation in vitro. After noradrenaline was administered to mice in vivo, Per1 mRNA expression in the brain was examined. The concentrations of serum IL-6, hs-CRP and plasma noradrenaline were elevated in OSAS patients, but improved by CPAP therapy. Per1 mRNA expression in the peripheral blood at 2:00 h significantly decreased by CPAP in OSAS patients. The stimulation with IL-6 did not directly induce Per1 mRNA in vitro. The administration of noradrenaline induced Per1 mRNA in cerebral cortex of mice in vivo. We first revealed that OSAS caused clock gene dysfunction, and CPAP helped to improve it. Sympathetic activation and elevation of the plasma noradrenaline concentration in OSAS may be one of the factors involved in disorders of Per1 mRNA expression.

时钟基因调节哺乳动物的昼夜节律，时钟基因的功能障碍会导致各种疾病。为了研究阻塞性睡眠呼吸暂停综合征（OSA）是否影响时钟基因的功能，我们检查了体外和体内的operc1（per1）mRNA表达。在8名健康受试者和8例OSAS患者中，我们测量了血浆去甲肾上腺素，血清IL-6和高敏化CRP（HS-CRP）以及周围全血的PER1 mRNA表达。在体外IL-6或去甲肾上腺素刺激下检查了PER1 mRNA在培养细胞中的表达。在体内给予去甲肾上腺素后，检查了大脑中的PER1 mRNA表达。 OSAS患者的血清IL-6，HS-CRP和血浆去甲肾上腺素的浓度升高，但通过CPAP治疗提高了。 OSAS患者的CPAP在2:00 h时在2:00 h时在外周血中的PER1 mRNA表达显着降低。用IL-6刺激不会直接在体外诱导PER1 mRNA。去甲肾上腺素在体内小鼠脑皮质中诱导的PER1 mRNA。我们首先透露OSA引起了时钟基因功能障碍，CPAP有助于改善它。 OSA中血浆去甲肾上腺素浓度的交感神经激活和升高可能是PER1 mRNA表达疾病涉及的因素之一。

项目成果

Dexamethasone influences human clock gene expression in bronchial epithelium and peripheral blood mononuclear cells in vitro

• DOI: 10.1081/cbi-200062416
• 发表时间: 2005-01-01
• 期刊: CHRONOBIOLOGY INTERNATIONAL
• 影响因子: 2.8
• 作者: Burioka, N;Takata, M;Shimizu, E
• 通讯作者: Shimizu, E

Treatment with β_2-adrenoceptor agonist in vivo induces human clock gene, Perl, mRNA expression in peripheral blood.

体内β_2-肾上腺素受体激动剂处理诱导外周血中人类时钟基因Perl mRNA的表达。

• 发表时间: 2007
• 期刊: Chronobiol Int 24(1)
• 作者: Burioka N;et al.
• 通讯作者: et al.

Glucocorticoid administration increases hPer1 mRNA levels in human peripheral blood mononuclear cells in vitro or in vivo

• DOI: 10.1177/0748730405279866
• 发表时间: 2005-12-01
• 期刊: JOURNAL OF BIOLOGICAL RHYTHMS
• 影响因子: 3.5
• 作者: Fukuoka, Y;Burioka, N;Shimizu, E
• 通讯作者: Shimizu, E

Function of clock genes in disease: Influence of medication for bronchial asthma on circadian gene.

时钟基因在疾病中的功能：支气管哮喘药物对昼夜节律基因的影响。

• 发表时间: 2007
• 期刊: J Pharmacol Sci 103(2)
• 作者: Burioka N;Fukuoka Y;Takata M;Endo M;Miyata M;Chikumi H;Tomita K;Kodani M;Touge H;Takeda K;Sumikawa T;Yamaguchi K;Ueda Y;Nakazaki H;Suyama H;Yamasaki A;Sano H;Igishi T;Shimizu E
• 通讯作者: Shimizu E

β_2-adrenoceptor agonists induce the mammalian clock gene, hPer1, mRNA in cultured human bronchial epithelium cells in vitro

β_2-肾上腺素受体激动剂在体外培养的人支气管上皮细胞中诱导哺乳动物时钟基因 hPer1 mRNA

• 发表时间: 2005
• 期刊: Chronobiol Int 22(4)
• 作者: Takata M;Burioka N;et. al.
• 通讯作者: et. al.