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題名:長期光照變動對大白鼠生理功能的影響:由輪班引發的人類肥胖動物模式
作者:蔡宇哲 引用關係
作者(外文):Yu-Che Tsai
校院名稱:國立中正大學
系所名稱:心理學所
指導教授:蔡玲玲
學位類別:博士
出版日期:2009
主題關鍵詞:內部節律失序能量調節胰島素抗性肥胖insulin resistanceenergy regulationcircadian disruptionobesity
原始連結:連回原系統網址new window
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長期輪班工作者經常經歷外在時間線索(time cue)與內在約日節律(circadian rhythm)不同步而處於節律失序( circadian desynchronization) 的困擾。流行病學調查顯示輪班工作者有較高的機率罹患心血管疾病、糖尿病等慢性疾病,這暗示節律失序可能會影響生理健康。除此之外尚有伴隨工作時程輪替所造成的行為改變、家庭與社交生活、壓力等因素,亦可能直接或與節律失序交互作用下影響生理健康。輪班工作研究受限於人類受試者難以長期配合而無法釐清節律失序本身是否直接影響生理健康。因此本研究試圖以動物模式來模擬人類輪班工作常有的節律失序現象,藉此瞭解節律失序對生理系統的影響為何。
實驗一將11-12週大的雄性F344大白鼠隨機分派兩組(每組各8隻):光照變動組(LS)的亮暗週期為三天光亮時間為2100-0900,接著連續三天光亮時間為0900-2100,第7天為24小時全亮以銜接下一輪的亮暗週期變化;光照控制組(LC)前6天光亮時間皆為0900-2100,第7天為24小時全亮。持續13週共26次光照週期變動後發現:LS組動物在經歷光照位移的歷程中,其體溫、心跳與活動節律一直呈現節律失序的狀態,且其體重增加量與進食量皆顯著高於但活動量顯著低於LC組動物。此結果與人類輪班工作者常有肥胖的現象相符,由此結果來看本研究以長期光照變動的方式來作為人類輪班工作者的動物模式應為合適。
實驗二應用相同的操弄,當動物經歷26次光照週期位移後,待其約日節律
恢復再校準(re-entrainment)之後禁食19小時於ZT7(光亮後第8小時)進行葡萄糖耐受性測試(glucose tolerance test)與胰島素耐受性測試(insulin tolerance test),且測量脂肪量及纖瘦素。結果發現持續光照變動使動物進食與脂肪量皆明顯增加,未禁食纖瘦素濃度顯著較高,但在葡萄糖耐受性與胰島素敏感性上並未呈現組間差異。
本研究結果得知以長期光照週期變動的方式可使F344大鼠呈現如同輪班工作者的節律失序狀態,且會有進食量上升、體重上升、脂肪量增加的情形,但並未對動物胰島素敏感性產生影響。節律失序對不同動物生理健康的影響程度不一,除因動物品系、實驗操弄的不同外,節律失序可能對健康的動物影響不大,而對生理狀況較差、病變或肥胖體質的動物有惡化的效果。
Shift work is associated with increased morbidity of cardiovascular diseases, gastrointestinal disorders and obesity. Chronic circadian desynchronization, behavioral changes, social disturbances, and stress have been suggested to be involved in work shift-related health problems. Scientific evidence causally linking circadian desynchronization and physiological function is not well documented. In this study, we developed an animal model to simulate circadian desynchronization in shift workers. With this animal model, we investigated the impacts of circadian desynchronization on physiological function, particularly on energy regulation and insulin resistance.
In Experiment 1, young (11-12 weeks old) male F344 rats were randomly assigned to experimental (LS; 8 rats) and control (LC; 8 rats) groups. LS rats exposed to a 12-h shift of the light-dark (LD) cycle every 3 days for a total of 13 weeks. Continuous LD shifts were efficient in inducing circadian desynchronization in intraperitoneal temperature, heart rate, and activity rhythm, increasing body weight and food intake, and reducing daily activity. These results were comparable to the findings of metabolic problems associated with human shift workers. Therefore, continuous LD shifts appear to be an appropriate animal model for work shifts.
In Experiment 2, young (11-12 weeks old) male F344 rats underwent the similar lighting protocol in Experiment 1. After LS rats were reentrained to the LD cycle
during a recovery period following the 13 weeks of LD shifts, all rats were tested for glucose tolerance and insulin tolerance 7 h after the onset of light. Fat tissues and blood were sampled 3 days after the test. Compared to LC rats, LS rats ate more and had a greater abdominal fat mass, but did not show changes in glucose tolerance and insulin sensitivity.
The present study demonstrated that continuous LD shifts in F344 rats caused circadian desynchronization and elevated body weight gain, food intake and abdominal adipose, but did not affect glucose tolerance and insulin sensitivity. Circadian desynchronization might had less impact on healthy animals, but instead aggravated unhealthy animals’ conditions like illness and obese predisposition.
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