d-柠檬烯和l-柠檬烯对体外培养的妊娠大鼠子宫肌层的影响。
Effects of d- and l-limonene on the pregnant rat myometrium in vitro.
作者信息
Hajagos-Tóth Judit, Hódi Ágnes, Seres Adrienn B, Gáspár Róbert
机构信息
Róbert Gáspár, Szeged, H-6701, P.O. Box 121, Hungary,
出版信息
Croat Med J. 2015 Oct;56(5):431-8. doi: 10.3325/cmj.2015.56.431.
AIM
To study the effects of d- and l-limonene on pregnant rat myometrial contractility in vitro, and investigate how these effects are modified by other agents. D- and l-limonene (10(-13)-10(-8) M) caused myometrial contraction in a dose-dependent manner.
METHODS
Contractions of uterine rings from 22-day-pregnant rats were measured in an organ bath in the presence of d- or l-limonene (10(-13)-10(-8) M) and nifedipine (10(-8) M), tetraethyl-ammonium (10(-3) M), theophylline (10(-5) M), or paxilline (10(-5) M). Uterine cyclic adenosine monophosphate (cAMP) level was detected by enzyme immunoassay. Oxidative damage was induced by methylglyoxal (3×10(-2) M) and the alteration was measured via noradrenaline (1×10(-9) to 3×10(-5) M) -induced contractions.
RESULTS
Pre-treatment with nifedipine (10(-8) M), tetraethylammonium (10(-3) M), and theophylline (10(-5) M) attenuated the contracting effect of d- and l-limonene, while in the presence of paxilline (10(-5) M) d- and l-limonene were ineffective. The two enantiomers decreased the myometrial cAMP level, but after paxilline pretreatment the cAMP level was not altered compared with the control value. Additionally, l-limonene (10(-6) M) diminished consequences of oxidative damage caused by methylglyoxal (3×10(-2) M) on contractility, whereas d-limonene was ineffective.
CONCLUSION
Our findings suggest that l-limonene has an antioxidant effect and that both d-and l-limonene cause myometrial contraction through activation of the A2A receptor and opening of the voltage-gated Ca(2+) channel. It is possible that limonene-containing products increase the pregnant uterus contractility and their use should be avoided during pregnancy.
目的
研究右旋和左旋柠檬烯对妊娠大鼠离体子宫肌层收缩性的影响，并探究其他药物如何改变这些影响。右旋和左旋柠檬烯（10⁻¹³ - 10⁻⁸ M）以剂量依赖性方式引起子宫肌层收缩。
方法
在器官浴槽中测量来自妊娠22天大鼠的子宫环在存在右旋或左旋柠檬烯（10⁻¹³ - 10⁻⁸ M）以及硝苯地平（10⁻⁸ M）、四乙铵（10⁻³ M）、茶碱（10⁻⁵ M）或帕吉林（10⁻⁵ M）时的收缩情况。通过酶免疫测定法检测子宫环磷酸腺苷（cAMP）水平。用甲基乙二醛（3×10⁻² M）诱导氧化损伤，并通过去甲肾上腺素（1×10⁻⁹至3×10⁻⁵ M）诱导的收缩来测量变化情况。
结果
用硝苯地平（10⁻⁸ M）、四乙铵（10⁻³ M）和茶碱（10⁻⁵ M）预处理可减弱右旋和左旋柠檬烯的收缩作用，而在存在帕吉林（10⁻⁵ M）时，右旋和左旋柠檬烯无效。两种对映体均降低子宫肌层cAMP水平，但在帕吉林预处理后，cAMP水平与对照值相比未改变。此外，左旋柠檬烯（10⁻⁶ M）减轻了甲基乙二醛（3×10⁻² M）引起的氧化损伤对收缩性的影响，而右旋柠檬烯无效。
结论
我们的研究结果表明，左旋柠檬烯具有抗氧化作用，并且右旋和左旋柠檬烯均通过激活A2A受体和打开电压门控钙通道引起子宫肌层收缩。含柠檬烯的产品可能会增加妊娠子宫的收缩性，孕期应避免使用。
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