Saito Takumi, Yamamoto Yasuhiro, Feng Guo-Gang, Kazaoka Yoshiaki, Fujiwara Yoshihiro, Kinoshita Hiroyuki
From the Departments of *Oral and Maxillofacial Surgery, †Pharmacology, and ‡Anesthesiology, Aichi Medical University School of Medicine, Aichi, Japan.
Anesth Analg. 2017 Jun;124(6):2054-2062. doi: 10.1213/ANE.0000000000002102.
Periodontal inflammation causes endothelial dysfunction of the systemic artery. However, it is unknown whether the use of local anesthetics during painful dental procedures alleviates periodontal inflammation and systemic endothelial function. This study was designed to examine whether the gingival or systemic injection of lidocaine prevents oxidative stress-induced endothelial dysfunction of the systemic artery in rats with intermittent periodontal inflammation caused by lipopolysaccharides (LPS).
Some rats received 1500 µg LPS injections to the gingiva during a week interval from the age of 8 to 11 weeks (LPS group). Lidocaine (3 mg/kg), LPS + lidocaine (3 mg/kg), LPS + lidocaine (1.5 mg/kg), and LPS + lidocaine (3 mg/kg, IP) groups simultaneously received gingival 1.5 or 3 mg/kg or IP 3 mg/kg injection of lidocaine on the same schedule as the gingival LPS. Isolated aortas or mandibles were subjected to the evaluation of histopathologic change, isometric force recording, reactive oxygen species, and Western immunoblotting.
Mean blood pressure and heart rate did not differ among the control, LPS, LPS + lidocaine (3 mg/kg), and lidocaine (3 mg/kg) groups. LPS application reduced acetylcholine (ACh, 10 to 10 mol/L)-induced relaxation (29% difference at ACh 3 × 10 mol/L, P = .01), which was restored by catalase. Gingival lidocaine (1.5 and 3 mg/kg) dose dependently prevented the endothelial dysfunction caused by LPS application (24.5%-31.1% difference at ACh 3 × 10 mol/L, P = .006 or .001, respectively). Similar to the gingival application, the IP injection of lidocaine (3 mg/kg) restored the ACh-induced dilation of isolated aortas from rats with the LPS application (27.5% difference at ACh 3 × 10 mol/L, P < .001). Levels of reactive oxygen species were double in aortas from the LPS group (P < .001), whereas the increment was abolished by polyethylene glycol-catalase, gingival lidocaine (3 mg/kg), or the combination. The LPS induced a 4-fold increase in the protein expression of tumor necrosis factor-α in the periodontal tissue (P < .001), whereas the lidocaine (3 mg/kg) coadministration partly reduced the levels. Lidocaine application also decreased the protein expression of the nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox, which was enhanced by the gingival LPS (5.6-fold increase; P < .001).
Lidocaine preserved the aortic endothelial function through a decrease in arterial reactive oxygen species produced by nicotinamide adenine dinucleotide phosphate oxidase and periodontal tumor necrosis factor-α levels in rats with periodontal inflammation. These results suggest the beneficial effect of the gingival application of local anesthetics on the treatment of periodontal diseases on endothelial function of systemic arteries.
牙周炎症会导致全身动脉的内皮功能障碍。然而，在疼痛的牙科手术中使用局部麻醉剂是否能减轻牙周炎症和全身内皮功能尚不清楚。本研究旨在探讨牙龈或全身注射利多卡因是否能预防脂多糖（LPS）引起的间歇性牙周炎症大鼠的氧化应激诱导的全身动脉内皮功能障碍。
一些大鼠在8至11周龄期间每隔一周接受1500μg LPS牙龈注射（LPS组）。利多卡因（3mg/kg）、LPS + 利多卡因（3mg/kg）、LPS + 利多卡因（1.5mg/kg）和LPS + 利多卡因（3mg/kg，腹腔注射）组在与牙龈LPS相同的时间安排下，同时接受牙龈1.5或3mg/kg或腹腔注射3mg/kg的利多卡因。分离主动脉或下颌骨进行组织病理学变化、等长力记录、活性氧和蛋白质免疫印迹评估。
对照组、LPS组、LPS + 利多卡因（3mg/kg）组和利多卡因（3mg/kg）组之间的平均血压和心率无差异。LPS应用降低了乙酰胆碱（ACh，10至10mol/L）诱导的舒张（在ACh 3×10mol/L时差异为29%，P = 0.01），而过氧化氢酶可使其恢复。牙龈利多卡因（1.5和3mg/kg）剂量依赖性地预防了LPS应用引起的内皮功能障碍（在ACh 3×10mol/L时差异为24.5%-31.1%，P分别为0.006或0.001）。与牙龈应用相似，腹腔注射利多卡因（3mg/kg）恢复了LPS应用大鼠分离主动脉的ACh诱导的舒张（在ACh 3×10mol/L时差异为27.5%，P < 0.001）。LPS组主动脉中的活性氧水平增加了一倍（P < 0.001），而聚乙二醇 - 过氧化氢酶、牙龈利多卡因（3mg/kg）或联合应用可消除这种增加。LPS使牙周组织中肿瘤坏死因子 - α的蛋白表达增加了4倍（P < 0.001），而利多卡因（3mg/kg）联合应用可部分降低其水平。利多卡因应用还降低了烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基p47phox的蛋白表达，牙龈LPS可使其增强（增加5.6倍；P < 0.001）。
利多卡因通过降低牙周炎症大鼠中烟酰胺腺嘌呤二核苷酸磷酸氧化酶产生的动脉活性氧和牙周肿瘤坏死因子 - α水平来维持主动脉内皮功能。这些结果表明牙龈应用局部麻醉剂对治疗牙周疾病对全身动脉内皮功能具有有益作用。
