目的 探究丁香酚及甲基丁香酚的抗焦慮作用及機(jī)制。方法 90只雄性SPF級(jí)SD大鼠，隨機(jī)分為對(duì)照組，模型組，地西泮（1 mg/kg）組，丁香酚低、中、高劑量（10、20、40 mg/kg）組和甲基丁香酚低、中、高劑量（10、20、40 mg/kg）組，每組10只，對(duì)照組和模型組給予0.5% CMC-Na溶液，每只大鼠給藥1 mL，ig給藥，給藥7 d后，除對(duì)照組外，進(jìn)行高架十字迷宮實(shí)驗(yàn)。采用酶聯(lián)免疫法（ELISA）測(cè)定焦慮大鼠血清中沉默信息調(diào)節(jié)因子2相關(guān)酶1（SIRT1）、單胺氧化酶A（MAO-A）、兒茶酚-O-甲基轉(zhuǎn)移酶（COMT）、乙醛脫氫酶（ALDH）及醛糖還原酶（AR）的表達(dá)量，同時(shí)通過逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)（RT-PCR）檢測(cè)各組海馬體組織中相應(yīng)的基因表達(dá)水平。結(jié)果 丁香酚高劑量組大鼠進(jìn)入開放臂次數(shù)（OE）百分比和開放臂停留時(shí)間（OT）百分比顯著高于模型組（P<0.01），作用呈劑量相關(guān)性；隨著劑量的增加，甲基丁香酚表現(xiàn)出抗焦慮作用趨勢(shì)，但差異無(wú)統(tǒng)計(jì)學(xué)意義。與對(duì)照組比較，模型組大鼠SIRT1和MAO-A酶含量及基因表達(dá)顯著升高（P<0.05、0.01），丁香酚與甲基丁香酚均發(fā)揮顯著回調(diào)作用（P<0.01）。與對(duì)照組比較，模型組大鼠血清中ALDH與AR含量顯著下降，COMT含量顯著升高（P<0.01）；海馬組織中COMT與ALDH的基因表達(dá)顯著上調(diào)，AR的基因表達(dá)顯著下調(diào)（P<0.01）。與模型組比較，丁香酚可顯著回調(diào)血清COMT、ALDH及AR含量（P<0.05、0.01），甲基丁香酚顯著回調(diào)血清COMT、AR含量（P<0.05、0.01）；丁香酚與甲基丁香酚能夠顯著抑制焦慮大鼠海馬體COMT與ALDH的基因表達(dá)上調(diào)（P<0.01），甲基丁香酚顯著抑制AR的基因表達(dá)下調(diào)（P<0.05）。結(jié)論 丁香酚和甲基丁香酚抗焦慮活性良好，可通過調(diào)控SIRT1-MAO-A信號(hào)通路進(jìn)而影響單胺類神經(jīng)遞質(zhì)5-羥色胺（5-HT）的代謝以及兒茶酚胺代謝通路中COMT、ALDH及AR酶的活性和基因表達(dá)發(fā)揮作用。

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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