目的 探究丁香酚及甲基丁香酚的抗焦虑作用及机制。方法 90只雄性SPF级SD大鼠，随机分为对照组，模型组，地西泮（1 mg/kg）组，丁香酚低、中、高剂量（10、20、40 mg/kg）组和甲基丁香酚低、中、高剂量（10、20、40 mg/kg）组，每组10只，对照组和模型组给予0.5% CMC-Na溶液，每只大鼠给药1 mL，ig给药，给药7 d后，除对照组外，进行高架十字迷宫实验。采用酶联免疫法（ELISA）测定焦虑大鼠血清中沉默信息调节因子2相关酶1（SIRT1）、单胺氧化酶A（MAO-A）、儿茶酚-O-甲基转移酶（COMT）、乙醛脱氢酶（ALDH）及醛糖还原酶（AR）的表达量，同时通过逆转录-聚合酶链反应（RT-PCR）检测各组海马体组织中相应的基因表达水平。结果 丁香酚高剂量组大鼠进入开放臂次数（OE）百分比和开放臂停留时间（OT）百分比显著高于模型组（P<0.01），作用呈剂量相关性；随着剂量的增加，甲基丁香酚表现出抗焦虑作用趋势，但差异无统计学意义。与对照组比较，模型组大鼠SIRT1和MAO-A酶含量及基因表达显著升高（P<0.05、0.01），丁香酚与甲基丁香酚均发挥显著回调作用（P<0.01）。与对照组比较，模型组大鼠血清中ALDH与AR含量显著下降，COMT含量显著升高（P<0.01）；海马组织中COMT与ALDH的基因表达显著上调，AR的基因表达显著下调（P<0.01）。与模型组比较，丁香酚可显著回调血清COMT、ALDH及AR含量（P<0.05、0.01），甲基丁香酚显著回调血清COMT、AR含量（P<0.05、0.01）；丁香酚与甲基丁香酚能够显著抑制焦虑大鼠海马体COMT与ALDH的基因表达上调（P<0.01），甲基丁香酚显著抑制AR的基因表达下调（P<0.05）。结论 丁香酚和甲基丁香酚抗焦虑活性良好，可通过调控SIRT1-MAO-A信号通路进而影响单胺类神经递质5-羟色胺（5-HT）的代谢以及儿茶酚胺代谢通路中COMT、ALDH及AR酶的活性和基因表达发挥作用。

Objective To explore the anti-anxiety effect of eugenol and methyleugenol and its possible mechanisms. Methods Totally ninety male Sprague-Dawley Rats (SPF) were randomly divided into nine groups: control group, model group, diazepam (1 mg/kg) group, eugenol low, middle and high-dose (10, 20, and 40 mg/kg) group, methyleugenol low, middle and high-dose (10, 20, and 40 mg/kg) group. Then the coments of NAD-dependent deacetylase sirtuin-1 (SIRT1), monoamine oxidase-A (MAO-A), catechol-o-methyl transferase (COMT), acetaldehyde dehydrogenase (ALDH) and aldose reductase (AR) in serum of anxiety rats were determined by enzyme-linked immunosorbent assay (ELISA), at the same time, the corresponding gene expression level in hippocampus was detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results The percentage of OE and OT in eugenol high-dose group were significantly higher than those in model group (P < 0.01); With the increase of dosage, methyl eugenol showed the trend of anti anxiety effect, but the difference was not statistically significant. Compared with the control group, SIRT1 and MAO-A enzyme contents and mRNA levels in the anxiety model rats were significantly increased (P < 0.05 and 0.01), and eugenol and methyleugenol treatment reversed this trend (P < 0.01). The contents of ALDH and AR in serum of anxiety rats decreased significantly, while the contents of COMT increased (P < 0.01); The mRNA levels of COMT and ALDH were upregulated, while AR gene expression was down-regulated (P < 0.01). Compared with model group, eugenol reversed the change trend of COMT, ALDH and AR (P < 0.05, 0.01), and methyl eugenol significantly reversed the change trend of serum COMT and AR (P < 0.05, 0.01); Eugenol and methyl eugenol significantly inhibited the up regulation of COMT and ALDH gene expression in hippocampus of anxiety rats (P < 0.01), while methyl eugenol significantly inhibited the down regulation of AR gene expression (P < 0.05). Conclusion Eugenol and methyleugenol have good anti-anxiety activity. They can adjust the metabolism of 5- hydroxytryptamine (5-HT) by regulating SIRT1-MAO-A signal pathway and affect the enzyme activity and gene expression of COMT, ALDH and AR in the metabolic pathway of catecholamine.

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