地西泮与咪达唑仑对离体大鼠子宫平滑肌收缩功能的影响

目的比较苯二氮艹卓类药物(BDZ)地西泮和咪达唑仑对孕和未孕大鼠子宫平滑肌收缩的影响是否不同。方法分离、制备孕和未孕SD大鼠子宫平滑肌条,采用累积给药法在浴槽内加入地西泮和咪达唑仑0.01~300μmol.L-1,MedLab生物信号采集系统记录给药前后子宫平滑肌收缩幅度和频率。结果地西泮和咪达唑仑对孕和未孕大鼠子宫平滑肌的收缩幅度均呈浓度依赖性抑制,且咪达唑仑的抑制作用明显较地西泮强。对于未孕大鼠,地西泮和咪达唑仑抑制子宫平滑肌收缩的IC50分别为280.6和1.1μmol.L-1。对于孕大鼠,地西泮与咪达唑仑抑制子宫平滑肌收缩的IC50分别为52.2和28.2μmol.L-1。地西泮对子宫平滑肌收缩频率的影响较小,而咪达唑仑在高浓度时能完全抑制子宫平滑肌的收缩。结论咪达唑仑对未孕及孕大鼠子宫平滑肌收缩幅度和频率的抑制作用强于地西泮,尤其是对未孕大鼠子宫平滑肌,为临床选择BDZ药物用于分娩提供了实验依据。

Effects of diazepam and midazolam on contraction of rat uterine smooth muscles

AIM To compare effects of diazepam and midazolam on the isolated pregnant and nonpregnant rat uterine smooth muscles. METHODS Uterine strips from the pregnant and nonpregnant rats isolated and prepared. After contractions became regular, strips were exposed to cumulative concentrations (0.01-300 μmol·L^-1) of diazepam and midazolam. Contractile amplitude and frequency of the isolated uterine smooth muscles were recorded by MedLab Biological Signal Collection System. RESULTS Both drugs inhibited contractile amplitude in a concentration-dependent manner on myometrium from non-pregnant and pregnant rats. On myometrium of non-pregnant rats, the IC₅₀ of diazepam and midazolam was 280.6 and 1.1 μmol·L^-1, respectively. On myometrium of pregnant rats, the IC₅₀ of diazepam and midazolam was 52.2 and 28.2 μmol·L^-1, respectively. Diazepam had slight inhibitory effect on the contractile frequency, while midazolam completely depressed the contractile activity at the highest concentration. CONCLUSION The inhibitory effect of midazolam is stronger than that of diazepam, especially on the myometrium from nonpregnant rats, providing experimental basis for clinical use of midazolam on parturition.