Doxey D L, Cutler C W, Iacopino A M
Baylor College of Dentistry, Department of Biomedical Sciences, Dallas, TX 75266-0677, USA.
J Periodontol. 1998 Feb;69(2):113-9. doi: 10.1902/jop.1998.69.2.113.
Periodontitis is a chronic inflammatory disease characterized by a progression that is very much dependent on host response. The gingiva can be considered to be in a constant state of wounding (pathologic wounding by bacterial plaque) and a constant state of maintenance/repair. In this context, any metabolic disturbance in the host which compromises tissue repair/wound healing will exacerbate the progression of periodontitis. Diabetes presents an interesting example because two major complications of diabetes are delayed wound healing and periodontitis. Our previous studies indicate that delayed wound healing and periodontitis may be manifestations of a general systemic deficit in diabetes involving alteration of macrophage cytokine gene expression. The present study was designed to determine whether: 1) diabetes-induced metabolic alterations affect gingival cytokine levels; and 2) diabetes-induced metabolic alterations modify the gingival cytokine profile in periodontitis. Sprague-Dawley rats (N=12/group) were injected with streptozotocin (65 mg/kg) into the tail vein to induce diabetes (defined by blood glucose levels > 250 mg/dl) or received the injection vehicle or no treatment as controls. Periodontitis was induced in additional groups of diabetic and control rats by gavage with Porphyromonas gingivalis A7436. After 90 days, serum glucose was analyzed to document diabetes; alveolar bone level was measured to document severity of periodontitis; gingiva was harvested circumferentially from the first and second molars; and cytokines in gingival homogenates were assayed by ELISA using commercial kits. Cytokine levels were expressed as mean+/-SEM pg/microg protein. Diabetes alone did not alter the gingival cytokine profile for platelet-derived growth factor B (PDGF-B), interleukin 1-beta (IL-1beta), transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha). Periodontitis alone demonstrated a significant increase (P < 0.05) in levels of PDGF-B and IL-1beta. Diabetes superimposed on periodontitis prevented these increases. Thus, diabetes-induced metabolic alterations do not affect gingival cytokine levels per se; however, they do alter the normal host response to periodontitis through blockage of periodontitis-induced increases in PDGF-B and IL-1beta.
牙周炎是一种慢性炎症性疾病，其进展在很大程度上取决于宿主反应。牙龈可被认为处于持续的损伤状态（由细菌菌斑引起的病理性损伤）和持续的维持/修复状态。在这种情况下，宿主中任何损害组织修复/伤口愈合的代谢紊乱都会加剧牙周炎的进展。糖尿病就是一个有趣的例子，因为糖尿病的两个主要并发症是伤口愈合延迟和牙周炎。我们之前的研究表明，伤口愈合延迟和牙周炎可能是糖尿病中涉及巨噬细胞细胞因子基因表达改变的全身性缺陷的表现。本研究旨在确定：1）糖尿病诱导的代谢改变是否会影响牙龈细胞因子水平；2）糖尿病诱导的代谢改变是否会改变牙周炎中牙龈细胞因子谱。将Sprague-Dawley大鼠（每组N = 12只）尾静脉注射链脲佐菌素（65 mg/kg）以诱导糖尿病（定义为血糖水平> 250 mg/dl），或接受注射载体或不进行治疗作为对照。通过用牙龈卟啉单胞菌A7436灌胃，在另外的糖尿病大鼠和对照大鼠组中诱导牙周炎。90天后，分析血清葡萄糖以记录糖尿病情况；测量牙槽骨水平以记录牙周炎的严重程度；从第一和第二磨牙周围切取牙龈；并使用商业试剂盒通过ELISA测定牙龈匀浆中的细胞因子。细胞因子水平以平均±SEM pg/μg蛋白质表示。单独的糖尿病并未改变血小板衍生生长因子B（PDGF-B）、白细胞介素1-β（IL-1β）、转化生长因子-β（TGF-β）和肿瘤坏死因子-α（TNF-α）的牙龈细胞因子谱。单独的牙周炎显示PDGF-B和IL-1β水平显著升高（P < 0.05）。叠加在牙周炎上的糖尿病阻止了这些升高。因此，糖尿病诱导的代谢改变本身并不影响牙龈细胞因子水平；然而，它们确实通过阻断牙周炎诱导的PDGF-B和IL-1β升高来改变宿主对牙周炎的正常反应。
