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对低剂量链脲佐菌素处理小鼠胰岛中浸润的细胞毒性效应细胞的超微结构观察

Ultrastructural observations on cytotoxic effector cells infiltrating pancreatic islets of low-dose streptozocin treated mice.

作者信息

Papaccio G, Esposito V

机构信息

Institute of Anatomy, I School of Medicine, Naples, Italy.

出版信息

Virchows Arch A Pathol Anat Histopathol. 1992;420(1):5-10. doi: 10.1007/BF01605977.

DOI:10.1007/BF01605977
PMID:1531718
Abstract

The aim of this study was to observe the ultrastructural events, during the onset of diabetes mellitus in the low-dose streptozocin (LDS)-treated mouse model with emphasis on the infiltrating elements. Forty male C57 BL/6J mice were given 40 mg/streptozocin on 5 consecutive days and killed 5, 6, 7, 8, 9, 10, 15, and 18 days after the first injection. Results demonstrated that islet infiltration occurring in LDS-treated mice is characterized by a very early pre-infiltration state in which mononuclear phagocytes in islet capillary vessels were considerably increased in number. A new histopathological time sequence for the early insulitis is described, in which attraction of blood mononuclear phagocytes into the islet capillary lumen is the first step. During the successive stage, occurring on days 6-8 we observed that mononuclear phagocytes migrate through capillary and venule walls into the islet parenchyma, where they differentiate into tissue macrophages. It was only later (step 3) that these macrophages acquired novel properties, typical of their "activated state" and started to phagocytose islet beta-cell debris. These data suggest that during the pre-infiltration and early insulitis the mononuclear phagocyte system plays a key role in the onset of LDS diabetes.

摘要

本研究的目的是观察低剂量链脲佐菌素(LDS)处理的小鼠模型中糖尿病发病过程中的超微结构变化,重点关注浸润成分。40只雄性C57 BL/6J小鼠连续5天每天给予40mg链脲佐菌素,并在首次注射后5、6、7、8、9、10、15和18天处死。结果表明,LDS处理的小鼠中发生的胰岛浸润的特征是一种非常早期的预浸润状态,其中胰岛毛细血管中的单核吞噬细胞数量显著增加。描述了早期胰岛炎的一种新的组织病理学时间顺序,其中血液单核吞噬细胞被吸引到胰岛毛细血管腔是第一步。在随后的第6-8天阶段,我们观察到单核吞噬细胞穿过毛细血管和小静脉壁迁移到胰岛实质,在那里它们分化为组织巨噬细胞。只是在后来(步骤3),这些巨噬细胞才获得了其“活化状态”典型的新特性,并开始吞噬胰岛β细胞碎片。这些数据表明,在预浸润和早期胰岛炎期间,单核吞噬细胞系统在LDS糖尿病的发病中起关键作用。

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1
Ultrastructural observations on cytotoxic effector cells infiltrating pancreatic islets of low-dose streptozocin treated mice.对低剂量链脲佐菌素处理小鼠胰岛中浸润的细胞毒性效应细胞的超微结构观察
Virchows Arch A Pathol Anat Histopathol. 1992;420(1):5-10. doi: 10.1007/BF01605977.
2
Morphological observations on pancreatic islet blood vessels in low-dose streptozocin-treated mice.低剂量链脲佐菌素处理小鼠胰岛血管的形态学观察
J Anat. 1993 Feb;182 ( Pt 1)(Pt 1):45-53.
3
Gangliosides prevent insulitis but not islet B cell destruction in low-dose streptozocin-treated mice.神经节苷脂可预防低剂量链脲佐菌素处理小鼠的胰岛炎,但不能预防胰岛B细胞破坏。
Diabetes Res Clin Pract. 1993 Jan;19(1):9-15. doi: 10.1016/0168-8227(93)90139-v.
4
Early macrophage infiltration in mice treated with low-dose streptozocin decreases islet superoxide dismutase levels: prevention by silica pretreatment.低剂量链脲佐菌素处理的小鼠早期巨噬细胞浸润会降低胰岛超氧化物歧化酶水平:二氧化硅预处理可预防。
Acta Anat (Basel). 1991;142(2):141-6. doi: 10.1159/000147179.
5
An increase in superoxide dismutase counteracts islet vascular alterations in low-dose streptozocin-treated mice.超氧化物歧化酶的增加可抵消低剂量链脲佐菌素处理小鼠的胰岛血管改变。
Histochemistry. 1994 Mar;101(3):215-21. doi: 10.1007/BF00269547.
6
Intercellular adhesion molecule-1 (ICAM-1) expression in the islets of the non-obese diabetic and low-dose streptozocin-treated mouse.非肥胖型糖尿病和低剂量链脲佐菌素处理小鼠胰岛中细胞间黏附分子-1(ICAM-1)的表达
Histochemistry. 1994 Oct;102(4):317-21. doi: 10.1007/BF00269169.
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Low-dose streptozocin-induced diabetes in mice. Electron microscopy reveals single-cell insulitis before diabetes onset.低剂量链脲佐菌素诱导的小鼠糖尿病。电子显微镜检查显示糖尿病发病前存在单细胞胰岛炎。
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Pancreatic duct infiltration in the low-dose streptozocin-treated mouse.低剂量链脲佐菌素处理小鼠的胰腺导管浸润
Histol Histopathol. 1994 Jul;9(3):529-34.
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Insulitis and islet microvasculature in type 1 diabetes.1型糖尿病中的胰岛炎和胰岛微血管系统
Histol Histopathol. 1993 Oct;8(4):751-9.
10
Capillary area in early low-dose streptozocin-treated mice.早期低剂量链脲佐菌素处理小鼠的毛细血管区域
Histochemistry. 1990;95(1):19-21. doi: 10.1007/BF00737223.

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In vivo microscopy of murine islets of Langerhans: increased adhesion of transferred lymphocytes to islets depends on macrophage-derived cytokines in a model of organ-specific insulitis.小鼠胰岛的体内显微镜检查:在器官特异性胰岛炎模型中,转移淋巴细胞与胰岛的粘附增加依赖于巨噬细胞衍生的细胞因子。
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本文引用的文献

1
Preferential infiltration of macrophages during early stages of insulitis in diabetes-prone BB rats.在易患糖尿病的BB大鼠胰岛炎早期巨噬细胞的优先浸润。
Diabetes. 1988 Aug;37(8):1053-8. doi: 10.2337/diab.37.8.1053.
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Low-dose streptozocin-induced diabetes in mice. Electron microscopy reveals single-cell insulitis before diabetes onset.低剂量链脲佐菌素诱导的小鼠糖尿病。电子显微镜检查显示糖尿病发病前存在单细胞胰岛炎。
Diabetes. 1988 Jan;37(1):21-7. doi: 10.2337/diab.37.1.21.
3
Mechanisms of pancreatic beta-cell destruction in type I diabetes.1型糖尿病中胰腺β细胞破坏的机制。
Early insulitis and the islet vascular system.
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Diabetologia. 1993 Jul;36(7):682-3. doi: 10.1007/BF00404082.
4
An increase in superoxide dismutase counteracts islet vascular alterations in low-dose streptozocin-treated mice.超氧化物歧化酶的增加可抵消低剂量链脲佐菌素处理小鼠的胰岛血管改变。
Histochemistry. 1994 Mar;101(3):215-21. doi: 10.1007/BF00269547.
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Circulating monocytes are activated in newly diagnosed type 1 diabetes mellitus patients.新诊断的1型糖尿病患者循环中的单核细胞被激活。
Clin Exp Immunol. 1994 Dec;98(3):489-93. doi: 10.1111/j.1365-2249.1994.tb05517.x.
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Morphological observations on pancreatic islet blood vessels in low-dose streptozocin-treated mice.低剂量链脲佐菌素处理小鼠胰岛血管的形态学观察
J Anat. 1993 Feb;182 ( Pt 1)(Pt 1):45-53.
7
Pancreatic duct inflammatory infiltration in the nonobese diabetic (NOD) mouse.非肥胖型糖尿病(NOD)小鼠的胰腺导管炎性浸润
J Anat. 1994 Dec;185 ( Pt 3)(Pt 3):465-70.
8
The immunosuppressant FK506 inhibits the damage to mouse pancreatic islets induced by low dose streptozocin.免疫抑制剂FK506可抑制低剂量链脲佐菌素诱导的小鼠胰岛损伤。
Cell Tissue Res. 1994 Sep;277(3):573-8. doi: 10.1007/BF00300231.
9
Alterations of islet microvasculature in mice treated with low-dose streptozocin.低剂量链脲佐菌素处理的小鼠胰岛微血管的改变。
Histochemistry. 1992 May;97(4):371-4. doi: 10.1007/BF00270040.
10
Immunomodulation of low dose streptozocin diabetes in mice reveals that insulitis is not obligatory for B cell destruction.低剂量链脲佐菌素诱导的小鼠糖尿病免疫调节研究表明,胰岛炎并非B细胞破坏的必要条件。
J Anat. 1992 Dec;181 ( Pt 3)(Pt 3):403-7.
Diabetes Care. 1988 Nov-Dec;11 Suppl 1:16-23.
4
Distinct macrophage subpopulations in pancreas of prediabetic BB/E rats. Possible role for macrophages in pathogenesis of IDDM.糖尿病前期BB/E大鼠胰腺中不同的巨噬细胞亚群。巨噬细胞在胰岛素依赖型糖尿病发病机制中的可能作用。
Diabetes. 1988 Sep;37(9):1301-4. doi: 10.2337/diab.37.9.1301.
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Mouse models of insulin dependent diabetes: low-dose streptozocin-induced diabetes and nonobese diabetic (NOD) mice.
Diabetes Metab Rev. 1987 Jul;3(3):751-78. doi: 10.1002/dmr.5610030308.
6
Acetyl-homocysteine-thiolactone-induced increase of superoxide dismutase counteracts the effect of subdiabetogenic doses of streptozocin.乙酰高半胱氨酸硫内酯诱导的超氧化物歧化酶增加可抵消亚致糖尿病剂量链脲佐菌素的作用。
Diabetes. 1986 Apr;35(4):470-4. doi: 10.2337/diab.35.4.470.
7
Evidence for initial involvement of macrophage in development of insulitis in NOD mice.巨噬细胞在非肥胖糖尿病(NOD)小鼠胰岛炎发展中最初参与的证据。
Diabetes. 1988 Jul;37(7):989-91. doi: 10.2337/diab.37.7.989.
8
Administration of silica particles or anti-Lyt2 antibody prevents beta-cell destruction in NOD mice given cyclophosphamide.给予环磷酰胺的非肥胖糖尿病(NOD)小鼠中,注射二氧化硅颗粒或抗Lyt2抗体可预防β细胞破坏。
Diabetes. 1988 Jul;37(7):930-5. doi: 10.2337/diab.37.7.930.
9
Cytotoxic effector cells of the immune system.免疫系统的细胞毒性效应细胞。
Anat Embryol (Berl). 1989;180(2):109-19. doi: 10.1007/BF00309762.
10
Macrophage-mediated islet cell cytotoxicity in BB rats.BB大鼠中巨噬细胞介导的胰岛细胞细胞毒性
Diabetes. 1989 Oct;38(10):1329-31. doi: 10.2337/diab.38.10.1329.