Tikhomirova O V, Zybina N N, Kozhevnikova V V
Nikiforov Federal State Budgetary Institution «All-Russian Center of Emergency and Radiation Medicine», St. Petersburg, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2021;121(8):7-12. doi: 10.17116/jnevro20211210817.
Circadian rhythm of pineal melatonin production is paced by the thalamus suprachiasmatic nucleus (SCN) depending on the lighting conditions via signal transduction to pinealocytes beta-receptors. Melatonin is a natural regulator of many physiological processes, and the decrease of its synthesis leads to various diseases, in particular, insomnia and metabolic disorders. It is known that administration of beta-blockers reduces melatonin production, but the data showing clinical significance of melatonin reduction associated with beta-blockers administration are still contradictory.
The influence of long-term administration of beta-blockers to melatonin synthesis, sleep quality and vascular brain damage.
The main study group included 114 patients, aged 47-83, with cardiovascular diseases, who were under a complex therapy with long-term administration of beta-blockers. The comparison group included 110 patients with cardiovascular diseases, similar in age and sex, who did not receive beta-blockers in their complex therapy. The circadian dynamics of melatonin synthesis was observed by excretion of 6-sulfatoxymelatonin (6-SM), the major metabolite of melatonin, in three urinary samples (day, evening, night). All the patients underwent night polysomnography to assess the severity of sleep disorders. The severity of vascular brain damage was assessed using magnetic resonance imaging.
The analyses showed large variability in individual values of 6-SM circadian excretion of patients with cardiovascular diseases (from 0.9 to 133 μg/24h with a mid-point 16.8 μg/24h). A considerable decrease of 6-SM circadian excretion is detected in the group of patients taking beta-blockers comparing to those not Me [q 25; q 75]: 12.8 [6.2; 21.1] and 24.0 [12.5; 41.5] μg/24h, respectively (<0.001), with no differences in sleep values and severity of vascular brain damage. Comparing subgroups of patients with 6-SM circadian excretion lower and higher than 16.8 μg/24h showed a significant increase of sleep latency, decrease of rapid eye movement sleep (REM sleep), increasing number of gliosis foci in white matter of the brain with higher values of leptin, leptin/adiponectin ratio and glycohemoglobin in the group of patients with 6-SM circadian excretion ≤16.8 μg/24h.
A low level of endogenous melatonin is a risk factor for development of sleep structure and quality disorders, vascular white matter brain damages with a higher risk for metabolic disorders. Long-term beta-blockers administration decrease endogenous melatonin synthesis to 50% increasing the risk for insomnia and vascular brain damage, mostly in patients with lower initial level of 6-SM circadian excretion.: melatonin, 6-sulfatoxymelatonin, beta-blockers, insomnia, vascular white matter brain damage, leptin, adiponectin.
松果体褪黑素分泌的昼夜节律由丘脑视交叉上核（SCN）根据光照条件通过信号转导至松果体细胞β受体来调节。褪黑素是许多生理过程的天然调节剂，其合成减少会导致各种疾病，尤其是失眠和代谢紊乱。已知β受体阻滞剂的使用会减少褪黑素的分泌，但显示与β受体阻滞剂使用相关的褪黑素减少的临床意义的数据仍相互矛盾。
长期使用β受体阻滞剂对褪黑素合成、睡眠质量和脑白质损伤的影响。
主要研究组包括114例年龄在47 - 83岁之间患有心血管疾病且正在接受长期使用β受体阻滞剂的综合治疗的患者。对照组包括110例年龄和性别相似、在综合治疗中未接受β受体阻滞剂的心血管疾病患者。通过检测三个尿液样本（白天、傍晚、夜间）中褪黑素的主要代谢产物6 - 硫酸氧褪黑素（6 - SM）的排泄情况来观察褪黑素合成的昼夜动态变化。所有患者均接受夜间多导睡眠图检查以评估睡眠障碍的严重程度。使用磁共振成像评估脑白质损伤的严重程度。
分析显示心血管疾病患者6 - SM昼夜排泄的个体值差异很大（从0.9至133μg/24h，中位数为16.8μg/24h）。与未服用β受体阻滞剂的患者相比，服用β受体阻滞剂的患者组中6 - SM昼夜排泄量显著降低，分别为12.8 [6.2；21.1] 和24.0 [12.5；41.5]μg/24h（<0.001），睡眠值和脑白质损伤严重程度无差异。比较6 - SM昼夜排泄量低于和高于16.8μg/24h的患者亚组，发现6 - SM昼夜排泄量≤16.8μg/24h的患者组中睡眠潜伏期显著延长、快速眼动睡眠（REM睡眠）减少、脑白质中胶质增生灶数量增加，同时瘦素、瘦素/脂联素比值和糖化血红蛋白水平升高。
内源性褪黑素水平低是睡眠结构和质量障碍、脑白质损伤以及代谢紊乱风险增加的危险因素。长期使用β受体阻滞剂会使内源性褪黑素合成减少50%，增加失眠和脑白质损伤的风险，这在初始6 - SM昼夜排泄水平较低的患者中更为明显。：褪黑素、6 - 硫酸氧褪黑素、β受体阻滞剂、失眠、脑白质损伤、瘦素、脂联素
