在间歇性牙周炎大鼠中，利多卡因可预防氧化应激引起的动脉系统的内皮功能障碍
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Lidocaine Prevents Oxidative Stress-Induced Endothelial Dysfunction of the Systemic Artery in Rats With Intermittent Periodontal Inflammation
背景与目的
牙周炎症会引起全身动脉内皮功能障碍，然而，在牙科手术中使用局麻药是否会减轻牙周炎症和改善全身动脉内皮功能，目前尚不清楚。本研究旨在探讨在脂多糖（LPS）所致的间歇性牙周炎大鼠中，牙龈局部或全身注射利多卡因能否预防氧化应激引起的动脉系统的内皮功能障碍。
方 法
部分大鼠每间隔一周（从8周龄-11周龄）接受1500 µg LPS注射（LPS组）。利多卡因(3 mg/kg)， LPS + 利多卡因(3 mg/kg), LPS + 利多卡因(1.5 mg/kg)，及LPS + 利多卡因 (3 mg/kg, IP) 组牙龈处同时与LPS组相同时间点接受1.5 ， 3 mg/kg 或 IP 3 mg/kg 利多卡因注射。运用组织病理学改变、记录等长收缩力、活性氧簇及蛋白印迹技术对采集的离体主动脉或下颌骨进行评估。
结 果
对照组，LPS, LPS + 利多卡因 (3 mg/kg)及 利多卡因 (3 mg/kg) 组的平均血压和心率无差异，应用LPS（ACh, 10 - 10 mol/L）后减少了Ach诱导的血管扩张（ACh 3 × 10 mol/L时差异达29%），这种作用可被过氧化氢酶恢复。牙龈局部应用利多卡因（1.5和3 mg/kg）剂量依赖性地防止脂多糖引起的内皮功能障碍，与牙龈局部应用相似，腹腔注射利多卡因3 mg/kg恢复LPS大鼠乙酰胆碱引起的离体主动脉的扩张。与对照组相比，LPS组主动脉活性氧的水平2倍，而聚乙二醇过氧化氢酶、龈利多卡因（3毫克/千克）或联合用药则可逆转其增加。LPS使牙周组织中肿瘤坏死因子α的蛋白表达量增加4倍，而合用利多卡因（3 mg/kg）可部分减少其表达水平。利多卡因的应用也降低了烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基p47phox蛋白的表达，在LPS诱发的牙龈炎症中显著增强（5.6倍增加；P＜001）。
结 论
利多卡因通过减少牙周炎症中烟酰胺腺嘌呤二核苷酸磷酸氧化酶产生的活性氧和牙周肿瘤坏死因子α水平，保护主动脉内皮功能。本研究提示在牙周病的治疗中，牙龈局部麻醉有益于全身动脉内皮功能的。
原始文献摘要
Anesth Analg. 2017 Jun;124(6):2054-2062. doi: 10.1213/ANE.0000000000002102
Saito T1, Yamamoto Y, Feng GG
BACKGROUND:
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).
METHODS:
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.
RESULTS:
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).
CONCLUSIONS:
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.
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