Dygai A M, Skurikhin E G, Pershina O V, Ermakova N N, Krupin V A, Ermolaeva L A, Stakheeva M N, Choinzonov E L, Goldberg V E, Reikhart D V, Ellinidi V N, Kravtsov V Yu
E. D. Goldberg Research Institute of Pharmacology and Regene rative Medicine, Tomsk, Russia.
Tomsk Research Institute of Oncology, Tomsk, Russia.
Bull Exp Biol Med. 2016 Feb;160(4):474-9. doi: 10.1007/s10517-016-3200-1. Epub 2016 Feb 23.
The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing β-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL-1β and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor β-cells (CD45(-), TER119(-), c-kit-1(-), and Flk-1(-)), oligopotent progenitor β-cells (CD45(-), TER119(-), CD133(+), and CD49f(low)), and insulinproducing β-cells (Pdx1(+)). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin-Sca-1(+)c-kit(+)CD34(+)) relative to long-term cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5-fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice.
采用链脲佐菌素诱导的C57Bl/6小鼠糖尿病模型，研究胰岛素生成β细胞前体、造血干细胞和造血祖细胞在炎症中的作用。除了引发高血糖外，链脲佐菌素还提高了血清白细胞介素-1β和透明质酸水平，诱导胰腺胰岛组织水肿，并使其被炎症细胞（中性粒细胞、淋巴细胞和巨噬细胞）和成纤维细胞浸润。胰岛炎症伴有坏死过程，多能祖细胞β细胞（CD45(-)、TER119(-)、c-kit-1(-)和Flk-1(-)）、寡能祖细胞β细胞（CD45(-)、TER119(-)、CD133(+)和CD49f(低)）以及胰岛素生成β细胞（Pdx1(+)）数量减少。胰腺炎症之前，骨髓中短期造血干细胞（Lin-Sca-1(+)c-kit(+)CD34(+)）相对于长期细胞（Lin(-)Sca-1(+)c-kit(+)CD34(-)）数量增加，造血干细胞和祖细胞募集进入循环。将糖尿病C57Bl/6供体小鼠的骨髓造血干细胞和祖细胞移植到5-氟尿嘧啶诱导白细胞减少的受体CBA小鼠中，加速了受体小鼠粒细胞生成的再生。
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