离体子宫张力测定在药物生殖毒性研究中的应用

目的:建立药物生殖毒性研究中孕鼠离体子宫平滑肌张力的测定方法。方法:SD大鼠于妊娠第6~15天(GD6-15)给予受试物,在妊娠第20天(GD20)取子宫平滑肌,分别给予不同浓度缩宫素和硫酸镁溶液刺激,选择试验的最佳条件。在此基础上,测定不同剂量组孕鼠离体子宫平滑肌张力的变化情况,采用RM-6240BD多道生理信号采集处理系统分析数据,统计结果。结果:选择0.007 U/m L缩宫素、0.008 mol/m L硫酸镁为最佳刺激浓度。随着受试物剂量的增加,加入缩宫素后,各组妊娠子宫平滑肌的频率和张力均呈逐渐上升的趋势,而加入硫酸镁后,各剂量组妊娠子宫平滑肌的活动幅度、频率和张力均呈现降低的趋势,但各剂量组与溶媒对照组相比均未见明显差异(P0.05)。结论:本研究建立了孕鼠离体子宫平滑肌张力的测定方法,该方法可以更好的反映受试物对孕鼠子宫肌的毒性作用,更加全面的评价受试物的生殖毒性。

Application of Isolated Uterine Tension in the Study of Reproductive Toxicity of Drugs

Objective:To establish a method of detecting the tension of isolated pregnant rat myometrium strips in the reproductive toxicity of drugs.Methods:SD rats were treated with drugs on the 6th-15th(GD6-15) of gestation, the uterine smooth muscle was taken on the 20th(GD20) of gestation and treated with different concentrations of oxytocin and magnesiumsulfate solution to choose the best conditions for testing. Then the effect of different dosages of drugs on the activity of isolated uterus smooth muscle of pregnant rats were observed by RM-6240BD biological signaling system.Results:0.007 U/mL magnesium sulfate and 0.008 mol/mL oxytocin were selected as the best concentration. With the increase of drug dosage, the frequency and tension of pregnant uterine smooth muscle of each group all showed a rising trend. While after the treatment with magnesium sulfate, the amplitude, frequency and tension of uterine smooth muscle of each dose group tends to decrease, but no significant difference was found between each dose group and control group (P>0.05).Conclusion:A method for the determination of muscle tension from isolated uterus of pregnant rats was established, which could better reflect the toxicity of the test substances on pregnant rats'' uterine muscle and comprehensively evaluate the reproductive toxicity.