Atilla G, Sorsa T, Rönka H, Emingil G
Ege University, Faculty of Dentistry, Department of Periodontology, Izmir, Turkey.
J Periodontol. 2001 Mar;72(3):354-60. doi: 10.1902/jop.2001.72.3.354.
Gingival overgrowth (GO) is one of the most important side effects of cyclosporin A (CsA) medication, but its pathogenesis is not completely understood. The aim of this study was to identify and compare collagenase-2 (MMP-8), gelatinase-B (MMP-9), and neutrophil (PMN)-elastase levels in gingival crevicular fluid (GCF) from 15 renal transplant patients receiving CsA therapy and exhibiting CsA GO, 14 patients with gingivitis, and 10 periodontally healthy subjects.
Clinical data were obtained on plaque index, papilla bleeding index, and hyperplastic index from each site studied. GCF samples and clinical data were collected from: 2 sites exhibiting CsA GO (CsA GO+) and 2 sites not exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2 diseased sites in each patient with gingivitis; and 2 healthy sites in each subject with clinically healthy periodontium. CsA GO+ and CsA GO- sites were divided into 2 subgroups as clinically not inflamed (PBI = 0) and inflamed (PBI > or =1). GCF MMP-8, MMP-9, and PMN-elastase levels were analyzed by immunofluorometric assay.
GCF MMP-8 and -9 levels and clinical degrees of gingival inflammation in CsA GO+ sites were similar to those in diseased sites. However, GCF elastase levels were significantly lower in CsA GO+ sites compared to those in diseased sites. GCF MMP-8, -9 and PMN-elastase levels were not different between CsA GO- sites and healthy sites. Additionally, GCF MMP-8 and -9 levels in inflamed CsA GO+ sites were higher but not statistically significantly than those in diseased sites. In contrast, GCF PMN-elastase levels in inflamed CsA GO+ sites were significantly lower than the levels in diseased sites.
These results show that CsA therapy does not have a significant effect on GCF MMP-8 and MMP-9 levels, but the gingival inflammation seems to be the main reason for their elevations. However, low GCF PMN-elastase levels can be an important factor in the pathogenesis of CsA-induced gingival overgrowth. CsA therapy does not eliminate the potential use of GCF MMP-8 and -9 as future diagnostic markers of gingival inflammation.
牙龈增生(GO)是环孢素A(CsA)治疗最重要的副作用之一,但其发病机制尚未完全明确。本研究旨在鉴定并比较15例接受CsA治疗且出现CsA相关性牙龈增生的肾移植患者、14例牙龈炎患者和10例牙周健康受试者龈沟液(GCF)中胶原酶-2(MMP-8)、明胶酶-B(MMP-9)和中性粒细胞(PMN)弹性蛋白酶的水平。
获取所研究各部位的菌斑指数、乳头出血指数和增生指数等临床数据。从以下部位收集GCF样本和临床数据:每位接受CsA治疗的患者中2个出现CsA相关性牙龈增生的部位(CsA GO+)和2个未出现CsA相关性牙龈增生的部位(CsA GO-);每位牙龈炎患者的2个患病部位;每位牙周健康受试者的2个健康部位。CsA GO+和CsA GO-部位又分为临床未发炎(PBI = 0)和发炎(PBI≥1)两个亚组。采用免疫荧光分析法分析GCF中MMP-8、MMP-9和PMN弹性蛋白酶的水平。
CsA GO+部位的GCF中MMP-8和-9水平以及牙龈炎症的临床程度与患病部位相似。然而,CsA GO+部位的GCF弹性蛋白酶水平显著低于患病部位。CsA GO-部位与健康部位的GCF中MMP-8、-9和PMN弹性蛋白酶水平无差异。此外,发炎的CsA GO+部位的GCF中MMP-8和-9水平高于患病部位,但无统计学意义。相反,发炎的CsA GO+部位的GCF中PMN弹性蛋白酶水平显著低于患病部位。
这些结果表明,CsA治疗对GCF中MMP-8和MMP-9水平无显著影响,但牙龈炎症似乎是其升高的主要原因。然而,低GCF PMN弹性蛋白酶水平可能是CsA诱导牙龈增生发病机制中的一个重要因素。CsA治疗并未排除将GCF中MMP-8和-9作为未来牙龈炎症诊断标志物的潜在用途。