肝郁证雌性大鼠的动情期变化及柴胡疏肝散的防治作用

Changes of estrus in female rats with liver-stagnation pattern and effects of Chaihu Shugan San on its prevention and treatment

目的探查肝郁证雌性大鼠的证候学和动情周期的变化及柴胡疏肝散的防治作用。方法雌性大鼠随机分为正常组,模型组,柴胡疏肝散大、小剂量组,每组10只。肝郁证模型复制采用慢性束缚法。大鼠造模第2周末(造模第14天),柴胡疏肝散大、小剂量组分别给予柴胡疏肝散1.26g/(kg·d)和0.31 g/(kg·d)灌胃,每日1次,连续2周;模型组和正常组大鼠给予等量蒸馏水。记录造模期间各组大鼠的外观行为和动情周期(阴道涂片法)的变化,实验2周末和4周末做糖水偏嗜实验,实验4周末做旷场实验。结果模型组大鼠实验期间出现由早期多动兴奋、烦躁易怒逐渐变为扎堆少动,行动迟缓,饮食减少等表现;第2周和第4周糖水偏嗜度分别增加和降低(P<0.01),第4周旷场实验中中央区停留时间、穿格次数、直立次数均降低(P<0.01),出现明显的动情周期紊乱。柴胡疏肝散的防治作用:与模型组比较,柴胡疏肝散大剂量组大鼠外部一般行为的异常趋于适度,糖水偏嗜度增加(P<0.01),旷场实验中的中央区停留时间、穿格次数、直立次数均见增加(P<0.01),动情周期紊乱率明显下降(P<0.01);柴胡疏肝散小剂量组上述指标变化无明显差异(P>0.05)。结论慢性束缚法建立的雌性肝郁模型大鼠不仅表现有中医肝郁证的变化且伴有动情周期的紊乱,肝郁证的治疗代表方柴胡疏肝散对该模型大鼠的中医证候及性周期紊乱均有良好改善作用,且大剂量作用优于小剂量。

Objective To investigate the changes of estrous cycle and the preventive and therapeutic effects of Chaihu Shugan San（ Radix bupleuri liver-soothing Powder,CHSGS） in female rats with liverstagnation pattern. Methods Female rats were randomly divided into normal group,liver-stagnation group,high-dose CHSGS group（ H group）,and low-dose CHSGS group（ L group）（ n = 10 in each group）. Liver stagnation pattern was established by using chronic restraint stress for 4 weeks. After modeling for 14 days,rats in the H and L groups were given the investigated medicine at the dose of 1. 26 g/kg and 0. 31 g/kg（ equivalent to 2 and 0. 5 times of human dosage） respectively,once a day for 2 weeks. Rats in the model group and the normal group were given the same amount of distilled water. At week 2 and week 4,sucrose preference test（ SPT） was conducted; At week 4,open field test（ OFT）was performed. Rat estrous cycles were observed by using vaginal smears. General observation was usedthroughout the experiment. Results At week 2,compared with the normal group,the model group showed a state of hyperactivity,irritability,reduced and slower mobility,and reduced food-intake. SPT were higher at week 2 but decreased at week 4（ P 0. 01）. Estrous cycle disorders were also reduced（ P 0. 01）. Duration in central zone（ Index S）,cubicle-crossing counts（ Index C） and vertical movements（ Index N） decreased in OFT test（ P 0. 01）. Compared with the model group,the activities of the rats in the H group were more similar to the control group,with the duration in the central zone and vertical movements higher than those in the model group（ P 0. 01） and SPT decreased（ P 0. 01）.Disordered estrous cycles decreased in H group（ P 0. 01）. The above-mentioned changes were not observed in the L group（ P 0. 05）. Conclusion Behavior changes with estrous cycle disorders were observed in female rat with liver-stagnation model established by chronic restraints stress. Chaihu Shugan San appeared to be effective in relieving the symptoms and estrous cycle disorders. High-dose CHSGS was superior to low-dose CHSGS.