進階搜尋


 
系統識別號 U0026-0812200914023410
論文名稱(中文) 間斷性禁食及急性壓力對大鼠心血管功能變化之影響
論文名稱(英文) Effects of Intermittent Food Deprivation on Stress-Induced Changes in Cardiovascular Functions in Rats
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 95
學期 2
出版年 96
研究生(中文) 林靜宜
研究生(英文) Ching-I Lin
電子信箱 s3693106@mail.ncku.edu.tw
學號 s3693106
學位類別 碩士
語文別 中文
論文頁數 72頁
口試委員 指導教授-任卓穎
口試委員-陳洵瑛
召集委員-郭余民
中文關鍵字 約束性壓力  間斷禁食  心跳  平均動脈壓  脈搏壓  c-FOS  麩胺酸脫羧酵素67 
英文關鍵字 heart rate  restraint stress  intermittent food deprivation  mean arterial pressure  c-FOS  GAD67  pulse pressure 
學科別分類
中文摘要 食物限制是指在沒有營養不良的情況下限制攝食(熱)量。目前發現給予飲食限制尤其以間斷禁食的方式,在許多物種上有正面的好處,包括可以延長壽命、延緩與老化相關病程的變化、增加對醣類代謝及神經毒性的耐受性。之前研究發現,大白鼠給予長期間斷禁食會降低休息時心跳、血壓及交感神經的活性,並增加副交感神經的活性及對約束性壓力的耐受性。壓力反應雖為生物體因應周遭刺激的即時保護機制,但是當生物體壓力反應失衡時也會造成心臟血管疾病的產生。中樞調控心臟血管反應的腦區包括孤獨核、網狀腹外側核及下視丘的室旁核等,因此假設長期間斷禁食及再度恢復攝食均會對壓力誘發心臟血管反應有所影響,且會改變中樞調控心血管相關核區神經活性。我們使用雄性Wistar品系大白鼠為實驗動物,分為控制組、間斷禁食組(給予為期24週交替禁食的食物限制方式)和恢復攝食組(間斷禁食後不再禁食4週)。實驗過程中1)定期記錄大白鼠的攝食量及體重;2)利用無線遙控系統在動物清醒的情況下,觀察在急性及重複性約束性壓力前(休息狀況)、壓力中及壓力後心血管參數(心跳、平均動脈壓及脈搏壓)的變化;3)使用免疫染色方式觀察急性壓力前及解除壓力後一小時c-FOS和GAD67在不同腦區中的表現。結果顯示1) 間斷禁食期間平均每天每隻大白鼠的攝食量約為控制組的70%;2) 各組動物體重皆會隨著週齡增加而漸增,但是間斷禁食組及恢復攝食組在間斷禁食期間,體重上升幅度較控制組低。恢復攝食組則在回復正常攝食4週期間內,體重持續上升;3) 各組動物在壓力過程中相較於壓力前心血管參數皆明顯上升並且無適應現象;4) 各組動物心血管參數在解除壓力後一至二小時內相較於壓力中明顯下降,但未降至壓力前水準;5) 間斷禁食降低動物在壓力前各心血管參數、壓力中脈搏壓上升程度及壓力後平均動脈壓和脈搏壓,然而恢復攝食後各心血管參數都有回復或上升趨勢;6) 在解除急性或連續性壓力後,間斷禁食組三項心血管參數立即下降,且一至二小時內脈搏壓可回到壓力前的基準值,心跳則從第三次開始出現適應現象;控制組及恢復攝食組的心跳及平均動脈壓不降反升,且控制組的脈搏壓無法回到基準值,心跳則從第四次才開始出現適應現象;7) 恢復攝食組在解除急性壓力及連續性壓力後心跳及平均動脈壓持平或上升,並且無隨著壓力次數增加而適應的現象;8) 在解除壓力後孤獨核、網狀腹外側核及室旁核的c-FOS均較壓力前為高;9) 間斷禁食會減少壓力後孤獨核及網狀腹外側核中c-FOS增加的程度;10) 壓力或餵食方式均不影響孤獨核、網狀腹外側核、室旁核及海馬回神經細胞中GAD67的表現。總結來說,長期間斷禁食使得心臟血管參數對壓力誘發的反應較為溫和,而且也降低壓力引發的延腦中孤獨核及網狀腹外側核神經活性上升程度。恢復攝食後壓力誘發心血管參數的反應也跟著恢復。
英文摘要 Calorie restriction, especially intermittent food deprivation (IF), exerts a wide range of beneficial effects, including increases in life span, insulin sensitivity and neuronal resistance to kinate, and delayed occurrence of age-associated pathophysiological changes. Previous studies have reported that IF animals show reduced basal blood pressure, heart rate and sympathetic tone, and increased stress resistance and parasympathetic activity. Although the stress response is important for the survival of animals, an impaired ability to adapt to stress may contribute to the pathogenesis of cardiovascular disease. It was plausible to hypothesize that IF improved stress-induced cardiovascular changes and influenced the neuronal activity in certain brain regions related to the central control of cardiovascular performance, and that these IF-induced beneficial effects would diminish when switched to regular diet. Adult Wistar rats were divided into three groups: AL (ad libitum feeding for 24 weeks), IF (every other day feeding for 24 weeks), and IF/AL (IF feeding for 24 weeks and followed by 4 additional weeks of AL feeding). The food intake and body weight were recorded regularly. Moreover, a telemetric probe was implanted in certain rats one month before sacrifice to monitor their blood pressure under resting (pre-stress), stress, and post-stress conditions. The immobilization stress was performed by restraining the rat in a conical wire mesh for 60 minutes. Rats were sacrificed one hour after stress to collect various brain regions for immunostaining of c-FOS and GAD67 . Our results showed that 1) rats during IF period consumed 30% less food over time and had reduced body weights increase compared with AL rats; 2) stress induced heart rate and blood pressure elevation, but it did not adapt during repeated stress in three groups; 3) comparing with AL rats, IF rats showed reduced blood pressure and heart rate during resting and stressed conditions; 4) IF rats showed immediate reduction of blood pressure and heart rate when released from wire mesh and they recovered faster at the end of the third-time stress ; 5) IF rats showed reduced stress-induced c-FOS expression in NTS and RVLM . Taken together, the IF intervention ameliorated stress-induced cardiovascular responses, possibly by improving the baroreflex sensitivity.
論文目次 目錄
中文摘要 ---------------------------------------2
英文摘要 ---------------------------------------4
誌謝--------------------------------------------6
目錄--------------------------------------------7
圖目錄------------------------------------------8
I. 導論 ----------------------------------9
II. 實驗材料與方法 -----------------------12
實驗藥品及溶液之備製---------------------------12
實驗動物---------------------------------------13
餵食及實驗步驟---------------------------------13
手術步驟---------------------------------------14
生理參數紀錄及分析-----------------------------15
急性壓力及重複性壓力之模式---------------------15
實驗動物麻醉與犧牲-----------------------------16
腦之製備---------------------------------------16
腦組織之免疫組織染色---------------------------16
定量分析---------------------------------------17
統計分析---------------------------------------17
IV. 實驗結果------------------------------19
V. 討論----------------------------------30
VI. 參考文獻------------------------------35
表及圖-----------------------------------------39
附錄-------------------------------------------66
表及圖目錄
表一:比較控制組、間斷禁食組及回復飲食組在急性壓力前、中及壓力後一小時各項生理參數-----39
圖一:比較控制組、間斷禁食組及恢復攝食組實驗期間單日攝食量變化--------- 41
圖二:比較控制組、間斷禁食組及恢復攝食組在實驗期間之體重變化------------41
圖三:比較控制組在急性壓力前、中及壓力後一小時各項生理參數--------------43
圖四:比較間斷禁食組在急性壓力前、中及壓力後一小時各項生理參數----------45
圖五:比較恢復攝食組在急性壓力前、中及壓力後一小時各項生理參數----------47
圖六:比較控制組、間斷禁食組及回復飲食組在急性壓力前、中及壓力後一小時各項生理參數------49
圖七:比較控制組、間斷禁食組及恢復攝食組在壓力中最後五分鐘及剛解除壓力後十分鐘各項生理參數----51
圖八:比較控制組在重複性壓力前、中及壓力後二小時各項生理參數-------------53
圖九:比較間斷禁食組在重複性壓力前、中及壓力後二小時各項生理參數---------55
圖十:比較恢復攝食組在重複性壓力前、中及後二小時各項生理參數-------------57
圖十一:比較控制組及間斷禁食組在急性壓力前、解除壓力後一小時孤獨核及網狀腹外側核中c-FOS的表現--59
圖十二:比較控制組及間斷禁食組在急性壓力前、解除壓力後一小時室旁核及海馬回中c-FOS的表現--------61
圖十三:比較控制組及間斷禁食組在急性壓力前、解除壓力後一小時孤獨核、網狀腹外側核、室旁核及海馬回中GAD67的表現------------------------------64
附圖一:比較控制組及間斷禁食組在急性壓力前、解除壓力後半小時對不同劑量之苯甲麻黃素誘導血管收縮的反應曲線---------------------------------------68
附圖二:比較控制組及間斷禁食組在急性壓力前、解除壓力後半小時對不同劑量之乙醯膽鹼及亞硝基化合物誘導血管舒張的反應---------------------------70
參考文獻 Ahmet,I., R.Wan, M.P.Mattson, E.G.Lakatta, and M.Talan. 2005. Cardioprotection by intermittent fasting in rats. Circulation 112: 3115-3121.

Anson,R.M., Z.Guo, C.R.de, T.Iyun, M.Rios, A.Hagepanos, D.K.Ingram, M.A.Lane, and M.P.Mattson. 2003. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc. Natl. Acad. Sci. U. S. A 100: 6216-6220.

Benarroch,E.E. 2005. Paraventricular nucleus, stress response, and cardiovascular disease. Clin. Auton. Res. 15: 254-263.

Bowers,G., W.E.Cullinan, and J.P.Herman. 1998. Region-specific regulation of glutamic acid decarboxylase (GAD) mRNA expression in central stress circuits. J. Neurosci. 18: 5938-5947.

Bruce-Keller,A.J., G.Umberger, R.McFall, and M.P.Mattson. 1999. Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Ann. Neurol. 45: 8-15.

Cas,L.D., M.Metra, S.Nodari, M.Nardi, R.Giubbini, and O.Visioli. 1993. [Stress and ischemic heart disease]. Cardiologia 38: 415-425.

Dampney,R.A., M.J.Coleman, M.A.Fontes, Y.Hirooka, J.Horiuchi, Y.W.Li, J.W.Polson, P.D.Potts, and T.Tagawa. 2002. Central mechanisms underlying short- and long-term regulation of the cardiovascular system. Clin. Exp. Pharmacol. Physiol 29: 261-268.

Dampney,R.A. and J.Horiuchi. 2003. Functional organisation of central cardiovascular pathways: studies using c-fos gene expression. Prog. Neurobiol. 71: 359-384.

Dampney,R.A., J.Horiuchi, S.Killinger, M.J.Sheriff, P.S.Tan, and L.M.McDowall. 2005. Long-term regulation of arterial blood pressure by hypothalamic nuclei: some critical questions. Clin. Exp. Pharmacol. Physiol 32: 419-425.

Dhahbi,J.M., P.L.Mote, J.Wingo, B.C.Rowley, S.X.Cao, R.L.Walford, and S.R.Spindler. 2001. Caloric restriction alters the feeding response of key metabolic enzyme genes. Mech. Ageing Dev. 122: 1033-1048.

Dragunow,M. and H.A.Robertson. 1987. Kindling stimulation induces c-fos protein(s) in granule cells of the rat dentate gyrus. Nature 329: 441-442.

Duan,W., Z.Guo, and M.P.Mattson. 2001. Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice. J. Neurochem. 76: 619-626.

Duan,W. and M.P.Mattson. 1999. Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease. J. Neurosci. Res. 57: 195-206.

Duffy,P.H., J.E.Leakey, J.L.Pipkin, A.Turturro, and R.W.Hart. 1997. The physiologic, neurologic, and behavioral effects of caloric restriction related to aging, disease, and environmental factors. Environ. Res. 73: 242-248.

Esclapez,M., N.J.Tillakaratne, D.L.Kaufman, A.J.Tobin, and C.R.Houser. 1994. Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms. J. Neurosci. 14: 1834-1855.

Feldblum,S., M.G.Erlander, and A.J.Tobin. 1993. Different distributions of GAD65 and GAD67 mRNAs suggest that the two glutamate decarboxylases play distinctive functional roles. J. Neurosci. Res. 34: 689-706.

Fontana,L., T.E.Meyer, S.Klein, and J.O.Holloszy. 2004. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc. Natl. Acad. Sci. U. S. A 101: 6659-6663.

Grassi,G., G.Seravalle, M.Colombo, G.Bolla, B.M.Cattaneo, F.Cavagnini, and G.Mancia. 1998. Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans. Circulation 97: 2037-2042.

Guo,Z., A.Ersoz, D.A.Butterfield, and M.P.Mattson. 2000. Beneficial effects of dietary restriction on cerebral cortical synaptic terminals: preservation of glucose and glutamate transport and mitochondrial function after exposure to amyloid beta-peptide, iron, and 3-nitropropionic acid. J. Neurochem. 75: 314-320.

Herlihy,J.T., C.Stacy, and H.A.Bertrand. 1992. Long-term calorie restriction enhances baroreflex responsiveness in Fischer 344 rats. Am. J. Physiol 263: H1021-H1025.

Hunt,S.P., A.Pini, and G.Evan. 1987. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 328: 632-634.

Krantz,D.S., K.F.Helmers, C.N.Bairey, L.E.Nebel, S.M.Hedges, and A.Rozanski. 1991. Cardiovascular reactivity and mental stress-induced myocardial ischemia in patients with coronary artery disease. Psychosom. Med. 53: 1-12.

Krantz,D.S., W.J.Kop, H.T.Santiago, and J.S.Gottdiener. 1996. Mental stress as a trigger of myocardial ischemia and infarction. Cardiol. Clin. 14: 271-287.

Kushiro,T., F.Kobayashi, H.Osada, H.Tomiyama, K.Satoh, Y.Otsuka, H.Kurumatani, and N.Kajiwara. 1991. Role of sympathetic activity in blood pressure reduction with low calorie regimen. Hypertension 17: 965-968.

Kwon,M.S., Y.J.Seo, E.J.Shim, S.S.Choi, J.Y.Lee, and H.W.Suh. 2006. The effect of single or repeated restraint stress on several signal molecules in paraventricular nucleus, arcuate nucleus and locus coeruleus. Neuroscience 142: 1281-1292.

Lee,J., W.Duan, and M.P.Mattson. 2002. Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J. Neurochem. 82: 1367-1375.

Mager,D.E., R.Wan, M.Brown, A.Cheng, P.Wareski, D.R.Abernethy, and M.P.Mattson. 2006. Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB J. 20: 631-637.

Mattson,M.P. and R.Wan. 2005. Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J. Nutr. Biochem. 16: 129-137.

McEwen,B.S. 1998. Protective and damaging effects of stress mediators. N. Engl. J. Med. 338: 171-179.

Oparil,S. and A.Oberman. 1999. Nontraditional cardiovascular risk factors. Am. J. Med. Sci. 317: 193-207.

Pickering,T.G. 2001. Mental stress as a causal factor in the development of hypertension and cardiovascular disease. Curr. Hypertens. Rep. 3: 249-254.

Sabatino,F., E.J.Masoro, C.A.McMahan, and R.W.Kuhn. 1991. Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. J. Gerontol. 46: B171-B179.

Swan,P.B. 1997. To live longer, eat less! (McCay, 1934-1939). J. Nutr. 127: 1039S-1041S.
Thomas,J., H.Bertrand, C.Stacy, and J.T.Herlihy. 1993. Long-term caloric restriction improves baroreflex sensitivity in aging Fischer 344 rats. J. Gerontol. 48: B151-B155.

Wan,R., S.Camandola, and M.P.Mattson. 2003b. Intermittent fasting and dietary supplementation with 2-deoxy-D-glucose improve functional and metabolic cardiovascular risk factors in rats. FASEB J. 17: 1133-1134.

Wan,R., S.Camandola, and M.P.Mattson. 2003a. Intermittent food deprivation improves cardiovascular and neuroendocrine responses to stress in rats. J. Nutr. 133: 1921-1929.

Yang,H., M.Shi, J.Story, A.Richardson, and Z.Guo. 2004. Food restriction attenuates age-related increase in the sensitivity of endothelial cells to oxidized lipids. J. Gerontol. A Biol. Sci. Med. Sci. 59: 316-323.

Yu,Z.F. and M.P.Mattson. 1999. Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism. J. Neurosci. Res. 57: 830-839.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2008-09-12起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2008-09-12起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw