胰岛发生、发育和再生及相关基因的研究
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摘要
目的
探讨胰腺发育中胰岛细胞的分化、迁移和胰岛的形成，以及在此过程中相关基因表达的变化。对胰岛β细胞损伤后的胰岛再生机制进行初步研究，并检测了β细胞损伤后调控胚胎胰岛细胞分化发育的部分关键性基因Pdx-1、Ngn3、Nkx2.2及Nkx6.1的表达情况，为应用胰腺干细胞作为糖尿病生物治疗性手段提供基础性研究。
材料和方法
1．收集征得孕妇签字同意后、因意外等各方面原因必须终止妊娠的不同胎龄段的正常胚胎标本进行组织学观察，并通过免疫组织化学方法观察胰岛细胞的分化发育和CD34、AFP、IGF-I、IGF-IR，TGF-β、TGF-βR，bFGF及FGFR因子在胰腺发育中的表达分布。
2．采用β细胞毒性剂—Alloxan腹腔注射破坏新生SD大鼠的β细胞，复制糖尿病模型，采用免疫组织化学方法观察胰岛β细胞的再生，并通过RT-PCR、Western-blot方法检测Pdx-1、Ngn3、Nkx2.2及Nkx6.1基因的表达。
结果
1．人胚胎观察
① 4周时，人胚胰芽由前肠末端发出，腹、背胰在胎龄5周时融
Objective
To clarify the differentiation and migration of islet cells as well as islet forming in pancreatic genesis and development, and the expressing changes of related genes in pancreatic development. Meanwhile, Initial investigation were established for mechanism of islets regeneration after β-cells injured. Part vital genes related to islet cells differentiation and development of embryo such as Pdx-1, Ngn3, Nkx2.2 and Nkx6.1 were detected in islets regeneration. It expected to provide elementary investigation for the biological application to finally cure diabetes mellitus. Material & Methods
Sample collection was conducted in accordance to the principle of informed consent. Histological method and immunohistological methods were adopted in studying normal embryonic pancreas of donators at 3-14 weeks of gestation, and analysis were made on vital cytokines expression of CD34, AFP, IGF-I, IGF-IR, TGF-β, TGF-βR, bFGF and FGFR for
探讨胰腺发育中胰岛细胞的分化、迁移和胰岛的形成，以及在此过程中相关基因表达的变化。对胰岛β细胞损伤后的胰岛再生机制进行初步研究，并检测了β细胞损伤后调控胚胎胰岛细胞分化发育的部分关键性基因Pdx-1、Ngn3、Nkx2.2及Nkx6.1的表达情况，为应用胰腺干细胞作为糖尿病生物治疗性手段提供基础性研究。
材料和方法
1．收集征得孕妇签字同意后、因意外等各方面原因必须终止妊娠的不同胎龄段的正常胚胎标本进行组织学观察，并通过免疫组织化学方法观察胰岛细胞的分化发育和CD34、AFP、IGF-I、IGF-IR，TGF-β、TGF-βR，bFGF及FGFR因子在胰腺发育中的表达分布。
2．采用β细胞毒性剂—Alloxan腹腔注射破坏新生SD大鼠的β细胞，复制糖尿病模型，采用免疫组织化学方法观察胰岛β细胞的再生，并通过RT-PCR、Western-blot方法检测Pdx-1、Ngn3、Nkx2.2及Nkx6.1基因的表达。
结果
1．人胚胎观察
① 4周时，人胚胰芽由前肠末端发出，腹、背胰在胎龄5周时融
Objective
To clarify the differentiation and migration of islet cells as well as islet forming in pancreatic genesis and development, and the expressing changes of related genes in pancreatic development. Meanwhile, Initial investigation were established for mechanism of islets regeneration after β-cells injured. Part vital genes related to islet cells differentiation and development of embryo such as Pdx-1, Ngn3, Nkx2.2 and Nkx6.1 were detected in islets regeneration. It expected to provide elementary investigation for the biological application to finally cure diabetes mellitus. Material & Methods
Sample collection was conducted in accordance to the principle of informed consent. Histological method and immunohistological methods were adopted in studying normal embryonic pancreas of donators at 3-14 weeks of gestation, and analysis were made on vital cytokines expression of CD34, AFP, IGF-I, IGF-IR, TGF-β, TGF-βR, bFGF and FGFR for
引文
1. Bonner-Weir, S., Taneja, M., Weir, G. C., Tatarkiewicz, K., Song, k. H., Sharma, A and O'Neil, J. J. In vitro cultivation of human islets from expanded ductal tissue. Proc Natl, Acad Sci, USA,2000,97:7999-8004
2. Ramiya, V. K., Maraist, M., Arfors, K. E., Schatz, D. A., Peck, A. B. and Cornelius, J. G. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat. Med, 2000,6:278-282
3. Soria, B., Roche, E., Berna, G., Leon-Quinto, T., Reig, J. A. and Martin, F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabets, 2000,49:157-162
4．徐庆，吴志勇．胰腺移植进展．肝、胆、胰外科杂志，2000，12(2)：111
5. L, ChArles Murtaugh, Douglas A. Melton. Genes, Signal, and Lineages in Pancreas Development. Annu. Rew. Cell Dev. Biol, 2003,19:71-89
6. Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3+cells are islet progenitors and are distinct from duct progenitors. Development, 2002,129:2447-57
7. Herrera, P. L. Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development, 2000,127:2317-2322
8. Gmyr V, Verr—loote J, Belaich S, et al. Adult human cytokeratin 19-positive cells re-express insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans. Diabetes, 2000, 49(10):1671-1680.
9. Nieto DA, Villar J, Matorras WR, et al. In tranterine growth retardation at tern: associatoon between anthropometric and endocrine patameters. Acta Obstet Gynecol Scand,1996; 75(2): 127.
10. Ale ssandro C, Giancarlo P Sergio F, et al. Effect of maternal carbohydrate metabolism on fetal growth. Obstet Gynecol,1998; 92(1):8.
11．卫朝霞，郑惠良，李杭生．人胎血清胰岛素含量测定．河南医科大学学报，2001，36(5)：596—597．
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2. Ramiya, V. K., Maraist, M., Arfors, K. E., Schatz, D. A., Peck, A. B. and Cornelius, J. G. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat. Med, 2000,6:278-282
3. Soria, B., Roche, E., Berna, G., Leon-Quinto, T., Reig, J. A. and Martin, F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabets, 2000,49:157-162
4．徐庆，吴志勇．胰腺移植进展．肝、胆、胰外科杂志，2000，12(2)：111
5. L, ChArles Murtaugh, Douglas A. Melton. Genes, Signal, and Lineages in Pancreas Development. Annu. Rew. Cell Dev. Biol, 2003,19:71-89
6. Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3+cells are islet progenitors and are distinct from duct progenitors. Development, 2002,129:2447-57
7. Herrera, P. L. Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development, 2000,127:2317-2322
8. Gmyr V, Verr—loote J, Belaich S, et al. Adult human cytokeratin 19-positive cells re-express insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans. Diabetes, 2000, 49(10):1671-1680.
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