桃红四物汤及配伍药对桃仁-红花与四物汤用于原发性痛经作用的比较研究

Study on compare Taohong Siwu Decoction,Taoren-Honghua pair and Siwu Decoction for primary dysmenorrhea

目的:基本方四物汤(SW)、衍化方桃红四物汤(THSW)及配伍药物对桃仁-红花(TH)用于妇科血瘀证原发性痛经的作用比较研究,以阐明方剂的配伍规律。方法:采用冰水浴及注射肾上腺素(0.8 ml/kg)的方法复制大鼠急性血瘀模型,灌胃给予5倍的临床剂量,对其血液流变性、凝血4项指标进行测定,HE染色光镜观察子宫、卵巢组织形态学变化;采用乙酰苯肼(10 mg/kg)及环磷酰胺(50 mg/kg)联合复制大鼠血虚模型,灌胃给予等效的临床剂量,对其外周血象、脏器指数进行测定及观察脾脏的形态学变化;采用小鼠注射苯甲酸雌二醇(0.01mg/g)和催产素(0.01ml/g)复制痛经模型,灌胃给予等效的临床剂量,观察并记录给催产素后30 min内小鼠扭体反应发生的次数及对子宫组织匀浆中Ca2+和NO含量进行测定。结果:在大鼠急性血瘀模型中,5倍临床剂量的桃红四物汤(22.95 g生药/kg)可以显著降低低切变率时全血黏度,延长凝血时间;5倍临床剂量的桃仁-红花(6.75 g生药/kg)可以降低全血黏度、血浆黏度、血沉和红细胞压积,延长凝血时间、凝血酶原时间和部分活化凝血活酶时间及降低纤维蛋白原含量;5倍临床剂量四物汤的(16.2 g生药/kg)对血液流变各项指标影响不明显;5倍临床剂量的四物汤、桃红四物汤和TH对子宫、卵巢均有一定的保护作用。在大鼠血虚模型中,等效临床剂量的四物汤(3.24 g生药/kg)和桃红四物汤(4.59 g生药/kg)可以显著升高红细胞的数量,显著降低红细胞平均体积,对肝脏指数的恢复有显著的效果;等效临床剂量的SW对脾脏有一定的保护作用。等效临床剂量的桃仁-红花(1.35 g生药/kg)可以显著升高白细胞和血小板的数量。在小鼠痛经模型中,等效临床剂量的桃红四物汤(0.665 g生药/kg)可显著降低扭体次数,这可能与其显著降低子宫组织匀浆中Ca2+含量和显著增加NO含量有关;等效临床剂量的桃仁-红花(0.195 g生药/kg)可显著降低扭体次数,但机制不明。结论:本实验研究结果表明衍化方桃红四物汤配伍桃仁-红花后与基本方四物汤比较,保留了基本方的基本功效,并且有不同程度的增强趋势。

Objective： Compare Taohong Siwu Decoction,Taoren-Honghua herb pair and Siwu Decoction for primary dysmenorrhea of gynecologyblood stasis syndrome and clarify formulation rules.Methods： The rats were ice water soaked as stimulation for 5 min between 2 injections of epinephrine hydrochlorides to build rats＇ acute blood stasis mode and administrated 5 times of clinical dosage.Determine hemorheology and plasma coagulation and observe uterine and ovarian histological changes by HE staining.The rats were injected acetylphenylhydrazine and cyclophosphamidum to build rats＇ blood-deficient mode and administrated clinical dosage.Determine changes of peripheral hemogram and observe morphological change of spleen,thymus gland and liver.The rats were injected estrogens and oxytocin to build mice＇s primary dysmenorrhea mode and administrated clinical dosage..Observe writhing response in 30 min.Levels of Ca 2 ＋ and nitric oxide（NO） in primary dysmenorrheal model mice uterus were also been detected.Results： In rats＇ acute blood stasis mode,THSW could significantly decrease whole blood viscosity at low shear rate and prolong thrombin time.TH could decrease whole blood viscosity,plasma viscosity,erythrocyte sedimentation rate blood and packed cell volume and prolong thrombin time,prothrombin time and thromboplastin time and decrease fibrinogen content.However,SW had no effects on these indexes.SW,THSW and TH all had a good effect on uterine and ovarian histological changes.In rats＇ blood-deficient mode,SW and THSW could significantly increase RBC,increase MCV and liver index.SW also was in favor of spleen histological changes.TH could significantly increase WBC and PLT.In primary dysmenorrhea mode,THSW could decrease writhing response which was relation to decrease level of Ca 2 ＋ and increase level of NO.TH could also decrease writhing response but the mechanism was unknown.Conclusions： Compare to SW,THSW not only had function of SW but also had stronger effects on promoting blood circulation through influencing on hemorheology,plasma coagulation because of adding TH herb pair in THSW.