藍光對生理時鐘與睡眠的影響

Abstract

隨著科技的發展，現代人們在日常生活中非常頻繁的使用行動裝置，舉例來說，像是智慧型手機與平板電腦等，這些裝置都有螢幕，並且會發出強烈的藍光，藍光的能量在可見光中比較強，長時間的照射可能會導致感光受器受損並影響視覺，但另外重要的是，光線也會影響人類的生理行為，像是生理時鐘與睡眠。 睡眠在人類的生活中扮演重要的腳色，但目前對於睡眠如何產生、如何運作了解的並不多，目前認為影響睡眠有兩個重要的途徑，第一個是透過生理時鐘節律影響睡眠，第二個是透過生理穩態因子的平衡影響睡眠。外在光線變化對於睡眠會造成何種影響以及如何影響並不清楚，本實驗欲研究藍光對於睡眠結構與生理時鐘的影響。 實驗以大鼠作為動物模式，給予三種波長LED光源照射，波長分別為藍光(450-490 nm) 、橘光 (590 nm ~ 635 nm) 與紅光 (620 nm ~ 650 nm) ，照光時間8小時，強度500 lux± 100 lux，光源在12小時亮/暗期循環中額外給予，分為兩組，在暗期額外給予光照或是在亮期額外給予光照，額外照光當天以及照光後連續兩天記錄老鼠的腦波並分析睡眠。為了瞭解光線是如何影響睡眠，另外設計實驗測量褪黑激素在照光後的變化驗證生理時鐘影響睡眠的路徑，以酵素結合免疫吸附試驗 (ELISA) 測量血清中褪黑激素的濃度，在給予暗期藍光照射後選擇四個時間點 (ZT0、 ZT2、 ZT4、ZT6) 測量。 實驗結果發現若在暗期給予額外光照，不論藍光、橘光或紅光組別都在照光當下非快速動眼期睡眠顯著上升並在亮期開始時連續兩個小時下降，節律向後移動兩小時的現象，在這裡我們提出兩個假設：第一個可能是因為睡眠的互補效應導致睡眠量下降；第二個可能是因為光線直接作用於生理時鐘影響睡眠節律延後。在額外光照後兩天的睡眠百分比節律並無顯著差異，另外在亮期給予額外光照的組別不論照光當下或照光後連續兩天睡眠百分比並無顯著差異。 若進一步分析睡眠結構發現睡眠不同階段換的次數增加，NREM sleep bouts上升、duration下降，在額外照光當下與連續兩天睡眠有片段化的趨勢。在測量褪黑激素濃度的實驗中發現給予暗期藍光照射後濃度相對控制組維持在較低的水平且能夠維持至少6小時，代表生理時鐘有發生變化，但要確定生理時鐘的變化需要測量更多時間點。 不只是藍光，不同波長的光線對於睡眠百分比以及結構的影響幾乎相同，褪黑激素濃度被抑制代表生理時鐘確實有變化而且持續到ZT6，這些來自環境中的光線對於我們的生理行為都有著舉足輕重的影響。

In our daily life, we spend a lot of time using the mobile devices, such as smart phones and tablet PCs. People receive the emitted light from the mobile displays. The light is mainly composed by the spectrum of the blue light. The energy of blue light is strong, so it can directly act on photoreceptors and cause vision impairment. However, blue light may also exhibit impacts on human physiology and behaviors, such as the circadian rhythms and sleep-wake activities. In our study, we investigated the effects of different spectra of light on the sleep architecture and sleep circadian rhythm. We used rats as the animal model. Rats were received different LED light exposures, including the blue light (450 nm ~ 490 nm), orange light (590 nm ~ 635 nm) and red light (620 nm ~ 650 nm) during the last 8 hours of the dark period or the light period in a 12:12h light:dark cycle. The intensity of each light spectrum was 500 lux ± 100 lux. Sleep-wake activities were recorded. Then, we investigated the sleep alterations after the light exposures. We further used melatonin ELISA kit to measure the concentrations of melatonin in rat serum in four time points (ZT0, ZT2, ZT4, ZT6) after blue light exposure. Our result indicated that non-rapid eye movement (NREM) sleep was increased when we gave the 8-h light exposure in dark period. Sleep fluctuation was shift about 2-h after light exposure. If we analyze the sleep percentage in the following two days, we could not see any significant change. There was almost no difference between blue, orange and red light groups. In this case, we have two hypotheses to explain. The first explanation is that NREM sleep was increased during the 8-h light exposure during the dark period, there might be a decrease of NREM sleep in the following light period by a compensatory effect. The other reason is that the light effect directly affected circadian process to change the sleep pattern. On the other hand, the 8-h light exposure given during the light period did not significantly change sleep-wake activities. However, the sleep architectures, including sleep bouts, sleep duration and transition, were changed when rats receive the light exposure either during the dark period or during the light period. NREM bouts were increased, duration was decreased and transition number was increased, indicating sleep was fragmented. The sleep architectures recorded in the following two days also exhibited the fragmentation of sleep activity. We further investigated the change of melatonin concentrations in serum after light exposure and found that the concentrations of melatonin were declined when rats were received the blue light exposure in ZT0, ZT2, ZT4, and ZT6. Our result suggests that the alterations in the sleep architectures and sleep circadian rhythm differed when rats exposed to different light spectra in different zeitgeber times. The NREM sleep architecture became fragmented after light exposure. In blue light group, the melatonin concentration was in low level after blue light exposure. Despite of blue light, other spectrums of light also have effects on circadian rhythms and sleep. In our daily life, it is important to consider the light effect from our environment.