Abstract:

Objective To evaluate the expression of the receptor for advanced glycation end products (RAGE) in gingival tissue endothelial cells from type 2 diabetic rats with chronic periodontitis and to explore the role of RAGE in the pathogenesis of diabetes in cases with chronic periodontitis. Methods Sixty 7-week-old female Wistar diabetic obese rats were randomly divided into two groups. Periodontitis was induced in 30 rats by silk ligation, and the other 30 rats were used as the control group in which the periodontal tissues were not treated. One week after periodontal ligation and inoculation, the periodontitis and control group rats were randomly divided into two subgroups; the first subgroup was fed a high-fat diet, and the second group was fed a low-fat diet. Thus, 15 rats per group were included in the high-fat diet periodontitis (HF/P), low-fat diet periodontitis (LF/P), high-fat diet periodontal health (HF/C), and low-fat diet periodontal health (LF/C) groups. Glucose tolerance tests were performed weekly to measure the fasting insulin and blood glucose levels and the insulin resistance index to verify successful construction of the rat diabetes model. After successful modeling of chronic periodontitis, the rats were sacrificed at the 13th week after measurement of the serum necrosis factor-α (TNF-α), interleukin-6 (IL-6) and leptin levels. The tooth periodontal tissues were prepared and sectioned to observe histological changes. Immunofluorescence double staining was used to detect the density of RAGE-positive endothelial cells in the gingival tissues of the four groups. Results The serum fasting blood glucose and insulin levels and insulin resistance index were significantly higher in the HF/P and HF/C groups than in the LF/P and LF/C groups (P < 0.01). The serum TNF-α and IL-6 levels were significantly higher in the HF/P and LF/P groups than in the HF/C and LF/C groups (P < 0.01). The serum leptin levels were significantly higher in the HF/P group than in the other three groups. The density of RAGE-positive endothelial cells was significantly higher in the HF/P and HF/C groups than in the LF/P (P=0.001) and LF/C groups (P=0.040). The density of RAGE-positive endothelial cells in the HF/P group was higher than that in the HF/C group (P=0.027). Conclusion Endothelial cells in type 2 diabetic rats with periodontitis have increased gingival tissue RAGE and serum leptin levels.

Key words: type 2 diabetes mellitus, periodontitis, receptor for advanced glycation end products, endothelial cells, high fat diet, hyperglycaemia, leptin

摘要：

目的 观察晚期糖基化终产物受体（receptor of advanced glycation end products,RAGE）在2型糖尿病伴慢性牙周炎大鼠牙龈组织内皮细胞中的表达,探讨RAGE在糖尿病伴慢性牙周炎发病机制中的作用。方法 60只7周龄雌性Wistar糖尿病肥胖大鼠,随机分成2组,其中30只大鼠采用丝线结扎法诱导牙周炎;另外30只作为对照组,牙周不作处理。牙周结扎并完成种菌1周后,分别将牙周炎组和对照组大鼠再随机分成2个亚组,其中1组喂养高脂饲料,另外1组喂养低脂饲料;共4组大鼠,每组15只,分别是高脂饮食-牙周炎组（HF/P）、低脂饮食-牙周炎组（LF/P）、高脂饮食-牙周健康组（HF/C）、低脂饮食-牙周健康组（LF/C）。每周进行糖耐量实验,测量空腹胰岛素、血糖,计算胰岛素抵抗指数以判断大鼠糖尿病建模情况。在第13周末慢性牙周炎建模成功后,检测血清肿瘤坏死因子-α（tumor necrosis factor,TNF-α）、白细胞介素-6（interleukin-6,IL-6）、瘦素水平后处死大鼠。制作牙体牙周组织联合切片,观察牙周组织的组织学改变。免疫荧光双染色法检测4组大鼠牙龈组织RAGE阳性内皮细胞密度。结果 HF/P组、HF/C组血清空腹血糖、空腹胰岛素水平及胰岛素抵抗指数均分别显著高于LF/P组、LF/C组（P<0.01）;HF/P组及LF/P组血清TNF-α和IL-6水平分别显著高于HF/C组、LF/C组（P<0.01）;HF/P组血清瘦素水平显著高于其他3组。HF/P组和HF/C组牙龈组织中RAGE阳性内皮细胞密度较LF/P组（P=0.001）、LF/C组（P=0.040）分别显著增多。HF/P组中RAGE阳性内皮细胞密度高于HF/C组（P=0.027）。结论 2型糖尿病伴牙周炎大鼠患牙牙龈组织中内皮细胞表达RAGE增加,血清瘦素水平升高。

关键词: 2型糖尿病, 牙周炎, 晚期糖基化终产物受体, 内皮细胞, 高脂饮食, 高血糖, 瘦素