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【摘要】 　　【目的】观察疏肝方四逆散、养血健脾方归脾汤和理气化痰方温胆汤对慢性应激肝郁模型大鼠行为学的影响，以进一步探讨该模型的中医证候性质。【方法】选用SD大鼠40只，按10g/L蔗糖水摄取率分层随机分为5组，即正常对照组、模型组、四逆散组(剂量为5?6g·kg-1·d-1)、归脾汤组(剂量为19?6g·kg-1·d-1)、温胆汤组(剂量为8?05g·kg-1·d-1);采用慢性应激刺激方法复制肝郁证模型，观察各组大鼠体质量、血清皮质酮含量、10g/L蔗糖水摄取率和强迫游泳中静止时间。【结果】模型组大鼠血清皮质酮含量升高、蔗糖水摄取率降低、强迫游泳中静止时间延长,与正常对照组比较差异均有显著性意义(P<0?05或P<0?01);四逆散组可降低血清皮质酮含量、升高蔗糖水摄取率，缩短强迫游泳中静止时间，与模型组比较差异均有显著性意义(P<0?05或P<0?01);归脾汤组、温胆汤组各检测指标均无显著性改变(P>0?05)，各组大鼠体质量增加量比较均无显著性差异(P>0?05)。【结论】本研究的慢性应激大鼠模型属肝郁证模型，与心脾两虚及痰热内扰证无关。

【关键词】 慢性应激/中药疗法;肝郁证/中药疗法;四逆散/治疗应用;归脾汤/治疗应用;温胆汤/治疗应用;疾病模型，动物;大鼠

Abstract: ObjectiveTo observe the effects of Sini Powder (SP)，Guipi Decoction (GD) and Wendan Decoction (WD)，which have the actions of soothing liver，nourishing blood and strengthening spleen，and regulating Qi and resolving phlegm respectively，on the behavior of rat models with liver?Qi stagnation induced by chronic stress，and to explore the essence of traditional Chinese medical syndrome of this model.MethodsForty male Sprague?Dawley rats were exposed to an unpredictable sequence of mild stressors for 21 days while being treated by SP (5?6 g·kg-1·d-1)，GD (19?6 g·kg-1·d-1) or WD (8?05 g·kg-1·d-1).According to the intake rate of 10g/L sucrose solution，the rats were divided into normal control group，model group，SP group，GD group and WD group by stratified randomization.Body weight，standing time during forced swimming test and intake rate of 10g/L sucrose solution were investigated during the whole procedure.Serum corticosterone content was detected by enzyme?linked immunosorbent assay (ELISA).Results In the model group，serum corticosterone content was increased，intake rate of sucrose solution was reduced，and standing time during forced swimming test was prolonged (P<0?05 or P<0?01 compared with those in the normal control group).SP counteracted the above changes in the mode group (P<0?05 or P<0?01)，but GD and WD had no effect on the above indexes (P>0?05).The difference of body weight increase was insignificant between the 5 groups (P>0?05).Conclusion The rat model of liver?Qi stagnation can be induced by chronic stress，which is different from the syndromes of deficiency of both heart and spleen and the interior disturbance of phlegm?heat.

Key words: CHRONIC STRESS/TCD therapy;STAGNATION OF LIVER?QI/TCD therapy;SINI POWDER /therapeutic use;GUIPI DECOCTION/therapeutic use;WENDAN DECOCTION/therapeutic use;DISEASE MODELS，ANIMAL;RATS

证候是中医学现代研究的关键科学问题之一。由于影响证候的因素复杂、范围广泛以及伦理学等方面因素的制约，使证候发生发展机理的研究很难深入，建立证候动物模型是摆脱这一困境的重要途径。肝郁证是临床常见的基础性证候，已有用CCl4注射、艾叶注射或夹尾急性激怒法、模具限制法等多种制作肝郁证动物模型的报道[1]，但这些造模方法均因有种种缺陷，近年已很少应用。为了更好地模拟临床肝郁证，我们采用慢性应激的方法初步建立了肝郁证大鼠模型[2]，并从临床发病学特点、核心症状和3种治法代表方剂的治疗效应等方面，分析了该模型的合理性，初步认为其证候性质属肝郁且与脾虚无关[3-4]。在上述工作的基础上，本研究拟比较疏肝方四逆散、养血健脾方归脾汤和理气化痰方温胆汤对该模型大鼠的行为学效应，以进一步探讨该模型的中医证候性质。现报道如下。

1材料与方法

1?1药物、试剂及仪器

按照《方剂学》[5]确定方剂的组成，其中四逆散(《伤寒论》)：柴胡6g，枳实6g，生白芍6g，炙甘草6g;归脾汤(《济生方

》)：白术9g，茯苓9g，黄芪12g，龙眼肉12g，炒酸枣仁12g，人参6g，木香6g，炙甘草3g，当归9g，远志6g;温胆汤(《三因极一病证方论》)：半夏6g，竹茹6g，枳实6g，橘皮9g，炙甘草3g，茯苓4?5g。以上各方用饮用水将中药免煎颗粒(首创大地药业有限公司)按成人(以60kg计)1日用量的14倍配制成悬浊液，其中四逆散浓度为0?56g/mL，归脾汤浓度为1?96g/mL，温胆汤浓度为0?805g/mL。蔗糖(C12H22O11，分子量为342?29)购自北京化学试剂公司;皮质酮酶联免疫吸附试验(ELISA)测定试剂盒(批号：24110603)购自美国R&D公司。HY?2调速多用振荡器购自江苏金坛金城国胜实验仪器厂。

1?2动物、分组及给药