| Uterine contraction model in vitro is a common method forstudy of primary dysmenorrhea and its related drugs. Theuterine is taken away from rats or mice, and then placed intoa nutrient solution, simulate uterine contractions by addingthe modeling drug, the tension change of the uterus wasrecorded.Pathogenesis of dysmenorrhea has not yet been fullyelucidated，it is generally believed that primary dysmenorrheais most directly related to the hormone prostaglandin （PGE2,PGF2α, etc.）. PGF2αmay be closer to the primary dysmenorrheaon pathogenesis compared with oxytocin as the modeling drugs.Carboprost is a synthetic prostaglandin analogue ofPGF2α（15-methyl-PGF2α） with oxytocic properties, it＇ sconsidered to establish a new dysmenorrhea model in thisresearch.Phloroglucinol is a antispasmodic drugs for smooth muscleand it＇s gradually been promoted in clinical, mainly used forthe prevention of preterm birth and relieving acute spasmodicpain. However its mechanism still needs in—depth study.In this experiment, mice uterus is used to establish in vitro model to explore uterine contraction, carboprost isselected as a model drug to establish the isolated mouse uterinecontraction model, which can simulate dysmenorrhea. On thisbasis, this study explored the antispasmodic mechanism ofphloroglucinol. The specific contents are as follows:1. the optimization of carboprost induced model and thecomparison with oxytocin induced modelThe contractile force of in vitro mouse uterus increaseswith the elevated baseline, and MCF kept relatively steady withresting force ranged from0.2to1.0g.1.2g resting force seemednot to be appropriate, which made the MCF decreased andequilibration periods prolonged.The mice were randomly divided into two groups, mice inestradiol group were i.p estradiol benzoate0.2mg/d for3dwhile control group i.p equal volume of distilled water. Thespontaneous activity of control group is relatively weak withsignificant difference （p <0.01）. In estradiol group, thestandard deviation of MCF is relatively reduced, suggesting thehomogenization effect.Cumulative upgrade carboprost concentration, to drawcarboprost enhance isolated mouse uterine MCF dose—responsecurve, MCF increased with the concentration ranged from10—4mg/L to0.1mg/L.0.1mg/L carboprost made a significantdifference of MCF.In summary, the final selection of modeling condition is:female mice weighing18—22g, i.p estradiol benzoate0.2mg/d for continuous3d,0.5g of resting force,0.1mg/L carboprostinduced the contraction of in vitro uterine.0.1mg/L carboprost induced MCF was similar to5U/L oxytocin induced in isolated mouse uterine MCF in5to15minafter administration, there was not significant difference.2．Test of different drugs on the carboprost—induced in vitrodysmenorrhea model1×10-3mg/L of nifedipine can significantly inhibit themodel of uterine MCF, when nifedipine concentration rose to5×10-3mg/L, MCF was almost completely inhibited.Isoproterenol made a relatively short inhibition period ofMCF. The salbutamol similarly inhibit uterine contractions ofthis model,10μg/L salbutamol on MCF inhibition was71.1±10.4%10mg/L indomethacin or ibuprofen could not significantlyinhibit carboprost-induced uterine contractions in mice. Thismay be associated with mechanism of non—steroidalanti—inflammatory drug.3.Phloroglucinol antispasmodic mechanismsDifferent drugs were used to induce Uterine contraction,including5U/L oxytocin,0.1mg/L carboprost,2×10-6mol/L acetylcholine, then observe the impact of addedphloroglucinol. Phloroglucinol showed no significantinhibition of the in vitro mouse uterine contraction.On in vivo dysmenorrhea model of mice induced by the i.p20U/kg oxytocin,20mg/kg phloroglucinol can significantlyreduce the number of writhing, and it showed no significantdifference with130mg/kg indomethacin. The antispasmodicmechanism of phloroglucinol may be related to the metabolicprocesses in vivo. |
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