醒脾开郁方治疗抑郁症的临床及机制研究

【作者】 郭静；

【导师】 王永炎； 高颖；

【作者基本信息】 北京中医药大学 ， 中医内科， 2005， 博士

【摘要】 抑郁症(depression)指的是情感障碍,是一组以心境低落为主要特征的临床症状群,发病率有逐年增长的趋势,又因其具有高复发率、高自杀率等特点而日益引起医学界的广泛关注,西药抗抑郁治疗取得了显著进展,特别以近20 年最为迅速,而中医药在此领域的研究相对滞后,因此急需加大研究力度。 本研究通过对文献的梳理归纳,明确了“郁”的概念渊源,总结出历代医家治疗抑郁症的理论及经验规律,认为抑郁症的病因病机主要为气郁湿阻,情志抑郁则中焦脾胃气机不畅,影响其受纳运化、升清降浊功能,痰湿内生,蒙蔽神机而使神气衰退,脾胃运化失职则水谷精微化生无源而见神气不足,精神失养,临床表现为抑郁状态。提出了芳香化湿,醒脾开郁的治疗思路,方药以不换金正气散加减。 为了验证醒脾开郁方的有效性,并进一步探讨其有效机制,利用孤养与慢性轻度不可预见性刺激相结合的方法制作抑郁模型,从开野实验(OpenField)、动物强迫游泳实验等行为学角度观察其抗抑郁的作用。并应用高效液相色谱—电化学检测器观察了抑郁模型大鼠海马及皮层单胺类递质和其代谢产物的变化。结果显示:醒脾开郁方能显著缩短动物强迫游泳不动时间(p<0.05);OpenField 实验证明醒脾开郁方可明显改善动物的消极行为(p<0.01)。应用高效液相色谱—电化学检测器测定抑郁模型大鼠海马及皮层单胺类递质和其代谢产物的变化,结果显示模型大鼠海马及皮层 5-HT、海马 DA 含量明显降低(p<0.05),DA 的代谢产物 DOPAC、HVA 明显升高(p<0.05),并且模型组海马5-HIAA/5-HT、DOPAC/DA 及皮层 5-HIAA/5-HT 明显升高(p<0.05),皮层 5-HT/NE低于正常组(p<0.05),醒脾开郁方可升高海马和皮层的 5-HT 水平,降低海马 DOPAC、HVA,并可降低海马 DOPAC/DA,5-HIAA/5-HT 和皮层的 5-HIAA/5-HT比值。由此推论醒脾开郁方通过降低海马和皮层 5-HT 及 DA 的代谢,相对升高海马 5-HT、DA 及皮层 5-HT 含量而发挥抗抑郁作用。 抑郁症属于中医“郁病”范畴,临床表现多具有气郁湿阻的证候,本研究以氟西汀为对照组,研究醒脾开郁方治疗抑郁症的临床有效性,通过对 40 例患者的临床研究结果显示①据 HAMD 量表评定标准,治疗组治愈率和有效率分别为 35%和 75%。对照组治愈率和有效率分别为 40%和 65%,两组治愈率和有效率均无明显差别(p>0.05);根据中医证候疗效标准,治疗组治愈率 15%,有效率 80%,对照组治愈率 5%,有效率 55%,两组疗效无明显差别(p>0.05)。②症状评价:HAMD 量表总评分与治疗前比较,治疗组与对照组均具有统计学意义(p<0.001),两组间比较,无显著差异(p>0.05)。HAMD 总评分改善差值两组间比较,无统计学意义(p>0.05)。HAMD 因子与治疗前比较,治疗组与对照组的焦虑/躯体化因子及阻滞因子均有统计学意义(p<0.05),治疗组对睡眠因子和体重因子亦有显著改善- 2 - 醒脾开郁方治疗抑郁症的临床及机制研究(p<0.05),对照组对体重因子和睡眠障碍因子均无明显改善(p>0.05)。中医证候总评分与治疗前比较,治疗组与对照组均具有统计学意义(P<0.001)。③显效时间比较:疗后第 1 周治疗组 HAMD 总分、焦虑/躯体化因子、睡眠障碍因子、阻滞因子及中医证候量表评分较疗前比较差异均有统计学意义(p<0.05),对照组则在疗后 6 周与疗前有显著差异。治疗 1 周时治疗组的 HAMD 减分率大于 30%,对照组至 6 周时减分率大于30%, 认为治疗组治疗抑郁的显效时间在服药 1 周后,明显早于西药对照组。 综合以上资料,可以得出以下结论:气郁湿阻为抑郁症的发病基础,实验及临床证明以芳香化湿、行气调中为治则,采用醒脾开郁方治疗抑郁症疗效确切,其可能机制为通过调整中枢单胺类神经递质的代谢,而达到抗抑郁作用。临床观察表明醒脾开郁方与氟西汀在改善情感障碍方面疗效无明显差别,显效时间较西药明显提前,具有一定的优势。主题词:临床研究 机制研究 中医药治疗 抑郁症更多还原

【Abstract】 Depression refers to a kind of emotional disorder which consists of a group of symptoms characterized by emotional depression .It has been paid more attention by the medical circles these years for its higher sick rate,recurernce rate and possibility of disablement.In the recent 20 years,great advancement has been achieved in drug therapy.However,the study in treating depression with Chinese herb medicine is relatively backward.So it is necessary to strengthen the research in this area. In this study , the origion and course of the concept of “yu”was made explicit in tradional Chinese medicine (TCM)by classifying literature and summing up clinic experiences. It’s believed that pathogenic factor of depression is originated from stagnation of Qi and dampness. Emotional depression influences the Qi of ZhongJiao which results in insufficient digestion.And the function of elevating refined substances and lowering turbid essence are also reduced. Formation of dampness and phlegm will lead to mental confusion.And insufficient digestion will make spirit Qi reduced. So the clinic features is depressive.The therapeutic principle is removing dampness by means of aromatics,activating spleen Qi and relieving stagnation. The formula XingPiKaiYuFang(XF) is formed based on BuHuanJinZhengQiSan. Based on the classical depression animal model the reliability of XF was tested and the possible mechanism of antidepression was explored. The model was established by separation and chronic unpredictable mild stress. The antidepression effect of the formula was investigated from the point of behavor by Openfield test and forced swimming.And the content of monoamine neurotransmitters and its metabolites in rat hippocampus and cortex was observed by HPK-ECD. It has been proved that model rat’s and mice’s duration of immobility in forced swimming test was shortened by having XF(p <0.05),and By HPLC-ECD it was determined that content of 5-HT and DA in depressive rat’s hippocampus or cortex were lowered (p <0.05)and DOPAC HVA rised.DOPAC/DA 5-HIAA/5-HT of hippocampus and 5-HIAA/5-HT of cortex rised obviously (p<0.05)while 5-HT /NE of cortex lowered than that of the normal group.XF obviously increased 5-HT in cortex and hippocampus and decreased DOPAC and HVA in hippocampus .XF also decreased DOPAC/DA, 5-HIAA/5-HT of hippocampus and 5-HIAA/5-HT of cortex.So the possible antidepression mechanism of XF maybe involved in inhibiting the metabolism of 5-HT and DA in cortex and hippocampus ,and relatively increasing the level of 5-HT and DA in hippocampus and 5-HT in cortex . Depression belongs to “YuBing” in TCM.It is observed that most cases have the syndrome of stagnation of Qi and dampness.In the study, the effectiveness of XF was determined compared with fluoxetine by observing 40 cases of depression. Results showed that 7(35%)out of 20 patients were cured in the therapeutic group and 8(40%)out of 20 in the control group were cured according to HAMD effect criterion.The effective rate of the therapeutic group was 75% and it was 65% in the control group.There were not obvious difference in effect between the two groups.According to TCM syndrome effect criterion the cure rate and effective rate of the therapeutic group was 15% and 80%, while that of the control group was 5% and 55%,there was not obvious difference between the groups (p>0.05). According to symptom estimation,HAMD score of both the therapeutic group and the control group was significantly reduced compared with those before treating (p<0.001).There was not obvious difference between the two groups. HAMD score difference compared with those before treating of the two groups were similar(p>0.05). Compared with those before treating ,anxiety/somatization factor and retardation factor were all improved significantly in the two groups(p<0.05).Sleep disorder factor and weight factor were also improved in the therapeutic group(p<0.001).The control group had little effect in improving weight factor and sleep disorder factor (p>0.05). TCM syndrome score were also reduced significantly更多还原