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脂褐素

肝臟活體組織切片顯微照相圖片,圖中有許多脂褐素,使用H&E染色

脂褐素(英語:lipofuscin)的命名由來是具有顆粒狀的褐黃色色素[1],由含有脂肪的殘存物與溶酶體消化物所組成。被認為是一種隨著年紀增長或細胞操勞而增加的色素,可見於肝臟、腎臟心肌腎上腺神經細胞神經節細胞。主要分布在細胞核週圍,是脂色素的一種。

形成與流轉

脂褐素是不飽和脂肪酸氧化後的產物,也可能來自生物膜的降解、或是將運輸至粒線體或溶酶體的物質。除了有大量的脂肪成分外,脂褐素還有糖類金屬成份,包括[2]

類脂褐素的物質累積會造成脂褐素形成與排除間的不平衡:此種累積現象可以藉由對大鼠施打蛋白酶抑制劑而觀察到,但經過三個月後,可以發現老鼠的類脂褐素物質已回復到正常值,代表著大鼠有自體調節脂褐素物質的能力[3]。不過此一研究尚具爭議,主因是亮肽素促進產生的物質是否是一種脂褐素[4][5],因為早先的證據顯示真正的脂褐素在體外環境是不會降解的[6][7][8];但在體內是否能持續不被分解是存疑的。

相關疾病

脂褐素的積累是造成老年黃斑變性以及退化性眼球疾病不容忽視的危險因素。[9] 異常脂褐素的積累也會造成一系神經退行性疾病,稱為lipofuscinoses,例如神經元蠟樣脂褐素沉積症,也稱為巴廷疾病,以及一些其他的名稱。病理學上脂褐素的累積也與阿茲海默症帕金森氏病肌萎縮性脊髓側索硬化症、特定溶酶體疾病肢端肥大症慢性阻塞性肺病[10]中央核肌病。若脂褐素的積累在結腸內的狀況的原因是結腸黑變病

減少脂褐素積累的療法

卡路里限制飲食[2]維生素E[2]與增加穀胱甘肽均可以減少或停止脂褐質的產生。

研究指出,益智藥吡拉西坦可以減少大鼠組織累積脂褐素的量[11]

其他可能的療法:

濕性老年黃斑變性可以治療使用選擇性雷射脈衝小點加熱並殺死色素豐富的細胞,空出的空間可以讓健康細胞的繁殖。雷射也用於去除紋身、醫學美容也讓皮膚看起來更年輕。選擇性雷射去除脂褐質為生命延續領域的研究開闢了新的契機。

脂褐質的其他用途

脂褐素的定量是可應用於甲殼類動物例如龍蝦年齡鑑定。由於這些動物缺乏性部分,所以不能像硬骨魚類一樣,每年會增加在耳後的骨頭或耳石來計算年齡。年齡測定是瞭解魚類貝類的一項基本生物數據,如生長曲線。一些研究表明,量化的量存在脂褐素在眼柄可以提供年齡數值。不過這種方法尚未得到廣泛的應用,主要是由於水族館飼養的積累曲線與野外捕捉的積累曲線不太一致。

參考文獻

引用

  1. ^ 道兰氏医学词典中的lipofuscin
  2. ^ 2.0 2.1 2.2 Chris Gaugler, "Lipofuscin 互联网档案馆存檔,存档日期2007-07-15.", Stanislaus Journal of Biochemical Reviews May 1997
  3. ^ ML Katz, LM Rice and CL Gao, "Reversible accumulation of lipofuscin-like inclusions in the retinal pigment epithelium页面存档备份,存于互联网档案馆)", Investigative Ophthalmology & Visual Science, Vol 40,(1999) pp.175-181.
  4. ^ Alexei Terman and Ulf T. Brunk, "Is Lipofuscin Eliminated from Cells?页面存档备份,存于互联网档案馆)", Investigative Ophthalmology and Visual Science, (1999) vol. 40 pp.2463-2464.
  5. ^ Sallyanne Davies and Steven Ellis, "Lipofuscin Turnover页面存档备份,存于互联网档案馆)", Investigative Ophthalmology and Visual Science. (1999)40 pp.1887-1888
  6. ^ Terman, A, Brunk, UT. On the degradability and exocytosis of ceroid/lipofuscin in cultured rat cardiac myocytes. Mech Ageing Dev. 1998, 100 (2): 145–156. PMID 9541135. doi:10.1016/S0047-6374(97)00129-2. 
  7. ^ Terman, A, Brunk, UT (1998) "Ceroid/lipofuscin formation in cultured human fibroblasts: the role of oxidative stress and lysosomal proteolysis", Mech Ageing Dev 104, pp.277-291, PMID 9818731
  8. ^ Elleder, M, Drahota, Z, Lisá V, Mares V, Mandys V, Müller J, Palmer DN.(1995) "Tissue culture loading test with storage granules from animal models of neuronal ceroid-lipofuscinosis (Batten disease): testing their lysosomal degradability by normal and Batten cells" Am J Med Genet 57, pp.213-221, PMID 7668332
  9. ^ John Lacey, "Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration页面存档备份,存于互联网档案馆)", 23-May-2006
  10. ^ Muscle Nerve (2002) vol 25 pp.383-389
  11. ^ M. M. Paula-Barbosa, F. Brandao, M. C. Pinho, J. P. Andrade, M. D. Madeira, A. Cadete-Leite. The Effects of Piracetam on Lipofuscin of the Rat Cerebellar and Hippocampal Neurons after Long-Term Alcohol Treatment and Withdrawal: A Quantitative Study. Alcoholism: Clinical and Experimental Research. 1991-10, 15 (5): 834–838 [2022-10-21]. ISSN 0145-6008. doi:10.1111/j.1530-0277.1991.tb00610.x. (原始内容存档于2022-10-23) (英语). 
  12. ^ Roy D, Pathak DN, Singh R., "Effect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain.[失效連結]", Exp Gerontol. 1983;18(3):185-97.
  13. ^ Amenta F, Ferrante F, et all, "Reduced lipofuscin accumulation in senescent rat brain by long-term acetyl-L-carnitine treatment.页面存档备份,存于互联网档案馆)", Arch Gerontol Geriatr. 1989 Sep-Oct;9(2):147-53.
  14. ^ Huang SZ, Luo YJ, Wang L, Cai KY., "Effect of ginkgo biloba extract on livers in aged rats. [失效連結]", World J Gastroenterol. 2005 Jan 7;11(1):132-5.
  15. ^ 存档副本. [2009-06-14]. (原始内容存档于2009-04-11). 

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