研究生: |
許家棟 |
---|---|
論文名稱: |
蘭氏小島受損所誘發之血管周邊細胞網絡變化之定性與定量分析 3-D Characterization of the Reactive Perivascular Remodeling of Islet Schwann Cells and Pericytes in Injury |
指導教授: | 湯學成 |
口試委員: |
鍾元強
湯學成 莊峻鍠 |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
論文出版年: | 2013 |
畢業學年度: | 101 |
語文別: | 中文 |
論文頁數: | 54 |
中文關鍵詞: | 蘭氏小島 、胰島炎 、膠質細胞 、膠質細胞增生 、血管周細胞 |
相關次數: | 點閱:3 下載:0 |
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當胰小島受損時,其血管與神經網路的改變與重組,影響胰小島在糖尿病發病過程中的生理變化。然而,由於胰臟的不透明性,且胰小島位於胰臟的深處,這雙重的阻礙,使得光學顯微鏡在觀察胰小島血管與神經網路時受到限制。在另一方面,使用傳統切片機所獲得的二維光學顯微影像,只能將視野侷限在某一切面上,無法針對血管與神經網路的三維結構進行觀察。本實驗中我們使用三維影像技術,定性與定量分析神經組織之「膠質細胞網路」 (Schwann cell network)與「血管周細胞」 (pericytes) 在正常胰小島組織的型態,與其在糖尿病小鼠發病過程中的改變與重組。
在胰臟中,Schwann cells主要位於胰小島周邊,區隔內分泌與外分泌組織;pericytes則攀附於血管壁,並隨血管延伸。在中樞神經系統中,當腦與脊髓受損時,Schwann cells與pericytes同時啟動,形成glial scar控制受傷區域。但目前還不清楚在胰小島發炎時 -- 特別是在第1型糖尿病發病初期,當免疫系統開始破壞但未完全摧毀胰小島時 -- 是否有類似的細胞反應幫助胰小島賀爾蒙進入循環系統,維持生理機能運作。在本實驗中我們使用Schwann cells與pericytes的染色方法,並結合三維影像技術,觀察它們在胰小島發炎時於空間中的變化。我們並運用網路組織分析方法,進行第1型糖尿病小鼠模型,包括streptozotocin (STZ) 注射小鼠模型,與nonobese diabetic (NOD) 小鼠模型的胰臟組織影像分析。
從共軛焦顯微鏡的影像,我們觀察到正常小鼠中,膠質細胞網路會從蘭氏小島外圍往核心發展。施打STZ一周後的小鼠,蘭氏小島內微血管的周圍,膠質細胞會增生;同時血管周細胞的密度也會增加。NOD小鼠中,在早期與中期胰島炎,受損區域周圍以及微血管旁會有膠質細胞增生的情形;同時血管周細胞會聚集在受損區域中的喂養微動脈 (feeding arteriole) 上。
從蘭氏小島受損時,這些細胞的反應可以說明他們的可塑性,也說明當實驗性糖尿病對蘭氏小島造成損害時,膠質細胞與血管周細胞會對損傷進行立即性的補救。
[1] Merani S. "Optimal implantation site for pancreatic islet transplantation" Br J Surg. 2008 Dec; 95(12):1449-61.
[2] Gromada J, Franklin I, Wollheim CB. "Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. " Endocr Rev. 2007 Feb;28(1):84-116. Epub 2007 Jan 16.
[3] Taborsky GJ Jr. "Islets have a lot of nerve! Or do they?"Cell Metab. 2011 Jul 6;14(1):5-6.
[4] Regina E. Burris and Matthias Hebrok"Pancreatic Innervation in Mouse Development and β-cell Regeneration "Neuroscience. 2007 December 12; 150(3): 592–602.
[5]C. WOODS AND DANIEL PORTE, JR"Neural Control of the Endocrine Pancreas "Physiol Rev,1975.54(3):p.596-619
[6] Katherine Smith "Neurogastroenterology: Improving 3D imaging of the enteric nervous system"Nature Reviews Gastroenterology and Hepatology 8, 600 (November 2011)
[7] Fu, Y. Y. and S. C. Tang (2010). "At the movies: 3-dimensional technology and gastrointestinal histology." Gastroenterology 139(4): 1100-1105, 1105 e1101.
[8] José-Angel Conchello & Jeff W Lichtman"Optical sectioning microscopy"Nature Methods - 2, 920 - 931 (2005)
[9] Fu, Y. Y., C. H. Lu, et al. (2010). "Three-dimensional optical method for integrated visualization of mouse islet microstructure and vascular network with subcellular-level resolution." J Biomed Opt 15(4): 046018.
[10] Jeff W Lichtman & José-Angel Conchello "Fluorescence microscopy"Nature Methods - 2, 910 - 919 (2005)
[11] Wang, R.K. "Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents"IEEE Journal of Selected Topics in Quantum Electronics,2008.13(2):p.021101
[12] Valery V. Tuchin ; Ruikang K. Wang ; Alvin T. Yeh ;"Optical Clearing of Tissues and Cells"J. Biomed. Opt. 13(2), 021101 (April 23, 2008).
[13] Xiangqun Xu and Ruikang K Wang "Synergistic effect of hyperosmotic agents of dimethyl sulfoxide and glycerol on optical clearing of gastric tissue studied with near infrared spectroscopy. " 2004 Phys. Med. Biol. 49 457
[14] Fu, Y. Y. and S. C. Tang (2010). "Optical clearing facilitates integrated 3D visualization of mouse ileal microstructure and vascular network with high definition." Microvasc Res 80(3): 512-521.
[15] Collombat, P., X. Xu, et al. (2010). "Pancreatic beta-cells: from generation to regeneration." Semin Cell Dev Biol 21(8): 838-844.
[16] Lelio Orci a, RogerH Unger b "FUNCTIONAL SUBDIVISION OF ISLETS OF LANGERHANS AND POSSIBLE ROLE OF D CELLS"The Lancet, Volume 306, Issue 7947, Pages 1243 - 1244, 20 December 1975
[17] Cabrera, O., D. M. Berman, et al. (2006). "The unique cytoarchitecture of human pancreatic islets has implications for islet cell function." Proc Natl Acad Sci U S A 103(7): 2334-2339.
[18] Subhadra C. Gunawardana,et al."Imaging beta cell development in real-time using pancreatic explants from mice with green fluorescent protein-labeled pancreatic beta cells"JANUARY AND FEBRUARY 2005, Volume 41, Issue 1-2, pp 7-11
[19] Hideto Kojima , et al."Extrapancreatic insulin-producing cells in multiple organs in diabetes"February 24, 2004 vol. 101 no. 82458-2463
[20] Mary Kay Treutelaar,et al. "Nestin-Lineage Cells Contribute to the Microvasculature but Not Endocrine Cells of the Islet
"Diabetes October 2003 vol. 52 no. 102503-2512
[21] Xianquan Li,et al. "Islet Microvasculature in Islet Hyperplasia and Failure in a Model of Type 2 Diabetes
"Diabetes November 2006 vol. 55 no. 112965-2973
[22] Annika M. Svensson, et al."Age-induced changes in pancreatic islet blood flow: evidence for an impaired regulation in diabetic GK rats"AJP - Endo November 1, 2000 vol. 279 no. 5 E1139-E1144
[23] L. Jansson, P.-O. Carlsson "Graft vascular function after transplantation of pancreatic islets"Diabetologia June 2002, Volume 45, Issue 6, pp 749-763
[24] Marcela Brissova,et al."Pancreatic Islet Production of Vascular Endothelial Growth Factor-A Is Essential for Islet Vascularization, Revascularization, and Function"
Diabetes November 2006 vol. 55 no. 112974-2985
[25] Fu, Y. Y., C. H. Lu, et al. (2010). "Three-dimensional optical method for integrated visualization of mouse islet microstructure and vascular network with subcellular-level resolution." J Biomed Opt 15(4): 046018.
[26] Dosch, H. M., H. Tsui, et al. (2008). "Islet Glia, Neurons, and beta Cells The Neuroimmune Interface in the Pathogenesis of Type 1 Diabetes." Immunology of Diabetes V: From Bench to Bedside 1150: 32-42.
[27] Winer, S., H. Tsui, et al. (2003). "Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive." Nat Med 9(2): 198-205.
[28] Zhang, Y. Q. and N. Sarvetnick (2003). "Development of cell markers for the identification and expansion of islet progenitor cells." Diabetes Metab Res Rev 19(5): 363-374.
[29] Fawcett JW, Asher RA (1999) The glial scar and central nervous system repair. Brain Res Bull 49: 377-391
[30] Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50: 427-434
[31] Goritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisen J (2011) A pericyte origin of spinal cord scar tissue. Science 333: 238-242
[32] von Boyen GB, Steinkamp M, Reinshagen M, Schafer KH, Adler G, Kirsch J (2004) Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia. Gut 53: 222-228
[33] Cornet A, Savidge TC, Cabarrocas J, et al. (2001) Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease? Proc Natl Acad Sci U S A 98: 13306-13311
[34] Costantini TW, Bansal V, Krzyzaniak M, et al. (2010) Vagal nerve stimulation protects against burn-induced intestinal injury through activation of enteric glia cells. Am J Physiol Gastrointest Liver Physiol 299: G1308-1318
[35] Vasina V, Barbara G, Talamonti L, et al. (2006) Enteric neuroplasticity evoked by inflammation. Auton Neurosci 126-127: 264-272
[36] Kolb, H. (1987). "Mouse models of insulin dependent diabetes: low-dose streptozocin-induced diabetes and nonobese diabetic (NOD) mice." Diabetes Metab Rev 3(3): 751-778.
[37] Donev SR (1984) Ultrastructural evidence for the presence of a glial sheath investing the islets of Langerhans in the pancreas of mammals. Cell Tissue Res 237:343–348
[38] Sunami E, Kanazawa H, Hashizume H, Takeda M, Hatakeyama K, Ushiki T (2001) Morphological characteristics of Schwann cells in the islets of Langerhans of the murine pancreas. Arch Histol Cytol 64:191–201
[39] Hayden MR, Karuparthi PR, Habibi J et al (2008) Ultrastructure of islet microcirculation, pericytes and the islet exocrine interface in the HIP rat model of diabetes. Exp Biol Med (Maywood) 233:1109–1123
[40] Richards OC, Raines SM, Attie AD (2010) The role of blood vessels, endothelial cells, and vascular pericytes in insulin secretion and peripheral insulin action. Endocr Rev 31: 343-363
[41] Winer S, Tsui H, Lau A, et al. (2003) Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive. Nat Med 9: 198-205
[42] Teitelman G, Guz Y, Ivkovic S, Ehrlich M (1998) Islet injury induces neurotrophin expression in pancreatic cells and reactive gliosis of peri-islet Schwann cells. J Neurobiol 34: 304-318
[43] Nakamura M, Kitamura H, Konishi S et al (1995) The endocrine pancreas of spontaneously diabetic db/db mice: microangiopathy as revealed by transmission electronmicroscopy.Diabetes Res Clin Pract 30:89–100
[44] Hayden MR, Karuparthi PR, Habibi J et al (2007) Ultrastructural islet study of early fibrosis in the Ren2 rat model of hypertension.Emerging role of the islet pancreatic pericyte-stellate cell. JOP 8:725–738
[45] Denis MC, Mahmood U, Benoist C, Mathis D,Weissleder R (2004) Imaging inflammation of the pancreatic islets in type 1 diabetes. Proc Natl Acad Sci U S A 101:12634–12639
[46] Chiu YC, Hua TE, Fu YY, Pasricha PJ, Tang SC (2012) 3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury. Diabetologia 55: 3252-3261
[47] Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 7: 452-464
[48] Sandler S, Jansson L (1985) Vascular permeability of pancreatic islets after administration of streptozotocin. Virchows Arch A Pathol Anat Histopathol 407: 359-367
[49] Papaccio G (1993) Insulitis and islet microvasculature in type 1 diabetes. Histol Histopathol 8: 751-759
[50] Beppu H, Maruta K, Kurner T, Kolb H (1987) Diabetogenic action of streptozotocin: essential role of membrane permeability. Acta Endocrinol (Copenh) 114: 90-95
[51] Enghofer M, Usadel KH, Beck O, Kusterer K (1997) Superoxide dismutase reduces islet microvascular injury induced by streptozotocin in the rat. Am J Physiol 273: E376-382
[52] Papaccio G, Baccari GC, Strate C, Linn T (1994) Pancreatic duct inflammatory infiltration in the nonobese diabetic (NOD) mouse. J Anat 185 ( Pt 3): 465-470