原发性痛经寒凝血瘀证药效评价模型的建立

目的建立原发性痛经寒凝血瘀证大鼠模型,并在模型大鼠上,确定异丙肾上腺素诱导产热的最适剂量及催产素诱导子宫痉挛性收缩的最适剂量。方法 36只大鼠切除背部棕色脂肪7d后,丙硫氧嘧啶连续灌胃42d,术后21d开始雌激素连续灌胃28d,建立痛经寒凝血瘀证模型。在中性环境温度(28℃)下,d40乙醚浅麻醉苏醒后,生物机能检测系统连续监测尾静脉推注等比剂量异丙肾上腺素前30min和给药后120min,计算单位时间的温度曲线下面积,以给药前后单位时间曲线下面积的变化率计算诱导产热的ED50;d42水合氯醛麻醉下,尾静脉推注等比剂量的催产素,生物机能检测系统连续监测给药前后各30min的大鼠宫腔压力曲线下面积,以给药前后的面积变化率计算诱导宫缩的ED50。结果成功建立了原发性痛经寒凝血瘀证的大鼠模型。异丙肾上腺素诱导该模型大鼠产热的ED50为0.210μg·g-1,95%置信区间为0.167～0.264μg·g-1;催产素诱导宫缩的ED50为0.028U·g-1,95%置信区间为0.012～0.066U·g-1。结论建立了原发性痛经寒凝血瘀证的大鼠模型;在造模大鼠上,确定了异丙肾上腺素诱导适应性产热和催产素诱导子宫痉挛的最适剂量,作为评价原发性痛经痉挛性疼痛程度及其受局部温度影响的准确指标及观察条件。

A pharmacodynamic model for cold-painevaluation in rats with primary dysmenorrhea

Aim To calculate the median effective doses of isoprenaline inducing thermogenesis and oxytocin inducing uterine pressure for evaluating cold-pain pharmacodynamic action in rats with both primary dysmenorrheal and cold coagulating blood stasis.Methods From d 7 after the interscapular brown adipose tissue being removed,the 36 rats were administrated intragastricly with PTU(30 μg·g-1) for consecutive 42 days;and from d 21,the rats were administrated intragastricly with E(1 μg·g-1) for consecutive 28 days.The intrauterine temperature was monitored with electrophysiolograph 30 minutes before and 120 minutes after isoprenaline was administrated intravenously with 9 dosages at d 40(28℃ as the neutral environmental temperature) ;The intrauterine pressure was monitored with electrophysiolograph each 30 minutes before and after oxytocin was administrated intravenously with 9 dosages at d 42.The ratios were calculated from both AUC averages,ED50 was calculated from both of the logarithm dosages and ratios with the software Prism-4.Results A model for cold-pain in rats with primary dysmenorrhea was established.The ED50 of isoprenaline to induce uterine thermogenesis is 0.210 μg·g-1,and the 95% confidence interval is 0.167 ～ 0.264 μg·g-1;The ED50 of oxytocin to induce uterine contraction is 0.028 U·g-1,and the 95% confidence interval is 0.012 ～ 0.066 U·g-1.Conclusions A pharmacodynamic model for cold-pain evaluation in rats with primary dysmenorrhea is established.There are the optima of isoprenaline to induce thermogenesis and oxytocin to induce uterine contraction in this model rat,which can be used to evaluate the level of cold pain in primary dysmenorrheal.