1 型糖尿病使体内牙龈白细胞边缘和大分子渗出增强。
Type 1 diabetes predisposes to enhanced gingival leukocyte margination and macromolecule extravasation in vivo.
机构信息
Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA, USA.
出版信息
J Periodontal Res. 2010 Dec;45(6):748-56. doi: 10.1111/j.1600-0765.2010.01295.x.
BACKGROUND AND OBJECTIVE
Diabetes predisposes to periodontal disease. However, the cellular and molecular mechanisms linking the two conditions are not clear. The impact of chronic hyperglycemia on leukocyte margination and macromolecule extravasation was determined in gingival vessels in vivo.
MATERIALS AND METHODS
Gingival intravital microscopy was employed to measure extravasation of fluorescein isothiocyanate (FITC)-dextran in diabetic Akita and healthy wild-type (WT) mice. Rhodamine 6G and FITC-LY6G were injected for nonspecific and polymorphonuclear-specific leukocyte labeling, respectively. Surface expression of leukocyte adhesion molecules was determined with flow cytometry and western blotting.
RESULTS
Vascular permeability was significantly increased in Akita gingival vessels compared with WT [permeability index (PI): WT, 0.75 ± 0.05; Akita, 1.1 ± 0.03: p < 0.05). Wild-type gingival vessels reached comparable permeability 2 h after intragingival injection of tumor necrosis factor α (TNFα), used here as positive control (PI, 1.17 ± 0.16). The number of rolling leukocytes was significantly elevated in diabetic gingiva (WT, 25 ± 3.7 cells/min; Akita, 42 ± 8.5 cells/min; p < 0.03). Similar rolling cell counts were obtained in WT after intragingival injection of TNFα (10 ng TNFα, 47 ± 1.3 cells/min; 100 ng TNFα, 57.5 ± 5.85 cells/min). The number of leukocytes firmly attached to the endothelium was similar in WT and Akita mice. Leukocyte cell-surface expression of P-selectin glycoprotein ligand-1 and CD11a was increased in Akita mice, while L-selectin remained unchanged when compared with WT. Moreover, P-selectin expression in Akita gingival tissues was elevated compared with that of WT.
CONCLUSION
Chronic hyperglycemia induces a proinflammatory state in the gingival microcirculation characterized by increased vascular permeability, and leukocyte and endothelial cell activation. Leukocyte-induced microvascular damage, in turn, may contribute to periodontal tissue damage in diabetes.
背景与目的
糖尿病易患牙周病。然而，将这两种情况联系起来的细胞和分子机制尚不清楚。本研究旨在体内检测慢性高血糖对牙龈血管中白细胞边缘和大分子渗出的影响。
材料与方法
采用牙龈活体显微镜测量糖尿病 Akita 小鼠和健康野生型（WT）小鼠荧光素异硫氰酸酯（FITC）-葡聚糖的渗出量。分别用罗丹明 6G 和 FITC-LY6G 对非特异性和多形核白细胞进行标记。用流式细胞术和 Western blot 检测白细胞黏附分子的表面表达。
结果
与 WT 相比，Akita 牙龈血管的血管通透性显著增加[通透性指数（PI）：WT，0.75 ± 0.05；Akita，1.1 ± 0.03：p < 0.05）。WT 牙龈血管在注入肿瘤坏死因子-α（TNFα）后 2 小时达到类似的通透性（PI，1.17 ± 0.16），这里 TNFα 用作阳性对照。糖尿病牙龈的滚动白细胞数量明显增加（WT，25 ± 3.7 个/分钟；Akita，42 ± 8.5 个/分钟；p < 0.03）。WT 在注入 TNFα 后也获得了相似的滚动细胞计数（10ng TNFα，47 ± 1.3 个/分钟；100ng TNFα，57.5 ± 5.85 个/分钟）。WT 和 Akita 小鼠附着在血管内皮上的白细胞数量相似。与 WT 相比，Akita 小鼠白细胞表面的 P-选择素糖蛋白配体-1 和 CD11a 表达增加，而 L-选择素不变。此外，与 WT 相比，Akita 牙龈组织中的 P-选择素表达增加。
结论
慢性高血糖可诱导牙龈微循环产生促炎状态，表现为血管通透性增加、白细胞和内皮细胞激活。白细胞引起的微血管损伤反过来可能导致糖尿病牙周组织损伤。
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