Offenbacher S, Williams R C, Jeffcoat M K, Howell T H, Odle B M, Smith M A, Hall C M, Johnson H G, Goldhaber P
Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, Michigan.
J Periodontal Res. 1992 May;27(3):207-13. doi: 10.1111/j.1600-0765.1992.tb01670.x.
This investigation focuses on the changes in the concentrations of cyclooxygenase (CO) products present within the crevicular fluid in naturally-progressing periodontitis in the beagle and the effects of various non-steroidal anti-inflammatory drugs (NSAIDs) on these metabolite levels and disease progression. Six groups of 5-6 beagles with periodontitis were followed for 6 months to determine the pretreatment rate of radiographic bone loss. At baseline, groups of animals were placed on soft chow to promote disease progression. Groups were treated with either placebo, three different formulations of systemic ibuprofen, systemic naproxen or topical flurbiprofen. During the 6-month treatment phase, crevicular fluid (CF) samples and radiographs were taken at regular intervals. Radioimmunoassay of CF samples from untreated animals demonstrated a steady increase in prostaglandin E2 (PGE2) over baseline values. At 1 month, CF-PGE2 levels increased 2-fold over baseline and, by 6 months, had reached a 5- to 6-fold elevation. Crevicular fluid thromboxane B2 (CF-TxB2) levels rapidly reached a 4- to 5-fold peak over baseline at 1 month and subsequently dropped to a 2-fold elevation for the remainder of the study. The rate of bone loss (BLOSS) in untreated animals increased 38% during the 6-month period, as compared to baseline pretreatment BLOSS rates. Overall, there was a significant depression in the CF levels of both PGE2 and TxB2 in all NSAID-treated groups. All NSAID treatments significantly retarded BLOSS, ranging from 21.0-36.9% of the control BLOSS rate. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation.
本研究聚焦于比格犬自然进展型牙周炎龈沟液中环氧化酶(CO)产物浓度的变化,以及各种非甾体抗炎药(NSAIDs)对这些代谢物水平和疾病进展的影响。将六组5 - 6只患有牙周炎的比格犬随访6个月,以确定治疗前的放射学骨丢失率。在基线时,将动物分组并给予软食以促进疾病进展。各组分接受安慰剂、三种不同剂型的全身性布洛芬、全身性萘普生或局部用氟比洛芬治疗。在6个月的治疗阶段,定期采集龈沟液(CF)样本并拍摄X光片。对未治疗动物的CF样本进行放射免疫分析表明,前列腺素E2(PGE2)水平较基线值稳步升高。在1个月时,CF - PGE2水平比基线升高了2倍,到6个月时,升高至5至6倍。龈沟液血栓素B2(CF - TxB2)水平在1个月时迅速达到比基线高4至5倍的峰值,随后在研究的剩余时间降至高2倍的水平。与基线治疗前的骨丢失率相比,未治疗动物的骨丢失率(BLOSS)在6个月期间增加了38%。总体而言,所有NSAIDs治疗组的CF中PGE2和TxB2水平均显著降低。所有NSAIDs治疗均显著延缓了BLOSS,范围为对照BLOSS率的21.0 - 36.9%。此外,CO激活是骨破坏的一个主要调节步骤,因此可能是药物调节的一个重要靶点。