【作者】 王欣君；

【导师】 王玲玲；

【作者基本信息】 南京中医药大学 ， 针灸推拿学， 2009， 博士

【摘要】 【目的】SSRI_S抗抑郁药起效较慢,因此对抑郁症的病程和预后转归可能会带来一些问题。因为延迟起效会增加病人的致残或意外发生的危险性,而且抗抑郁药的副反应也会因起效慢而加重病情和降低依从性。因此,快速起效的抗抑郁治疗不仅可以减轻症状、减轻病人及其家属的痛苦,而且也会减少功能损害和降低自杀的危险性,同时,快速起效对抑郁症的社会经济负担减轻亦具重要意义。来自临床和实验研究发现:起效快(与SSRI_S相比较而言),是针灸治疗抑郁症的效应规律和特点之一,探索其中的机制,有利于进一步深入阐明针灸治疗抑郁症的机制,探讨针灸治疗抑郁症的作用特点,有利于寻找更加安全有效快捷的抗抑郁治疗措施。【方法】①将92例抑郁症患者随机分为针药结合组50例(针药组)和SSRI类抗抑郁药组42例(对照组)。采用汉密尔顿抑郁量表(HAMD),抑郁自评量表(SDS),匹兹堡睡眠质量指数(PSQI)量表和自制中医辨证分型症状评分量表评定疗效。②制作慢性应激模型抑郁症大鼠模型,随机分为药物组(氟西汀)、电针组、针药组,治疗7天时进行大鼠Open-Field法行为学评价、糖水消耗实验和real-time RT PCR法测定中缝核、海马、额叶皮质的5-TH1A受体mRNA、5-TH2A受体mRNA表达。【结果】①针药组与对照组比较,HAMD积分在第1、2、4周均有显著性差异(P＜0.01)。说明针药结合治疗抑郁症比SSRI类抗抑郁药起效快,疗效好。SDS积分在治疗前后无差异,但减分率有差异(P＜0.05)。针药组和对照组治疗后PSQI量表分值有明显下降(P＜0.05);治疗后针药组与对照组相比,PSQI量表分值差异有显著性意义(P＜0.05)。针药组与对照组比较,在睡眠质量、入睡时间、睡眠时间、睡眠效率、日间功能障碍五项上均有显著性差异(P＜0.01),但在睡眠障碍一项上无差异(P＞0.05)。从中医辨证分型症状评分来看,在治疗2周时,肝郁脾虚组与心脾两虚组疗效相当,脾肾阳虚组疗效较差(P＜0.01);治疗4周后三组证型积分无差异,但肝郁脾虚组减分率低于其它2组(P＜0.05)。②对于抑郁模型大鼠,治疗7天时各组行为学评分、体重和糖水消耗量比较,模型组、药物组、电针组、针药组的行为学评分、体重和糖水消耗量均低于正常组(P＜0.01)。模型组、药物组、电针组、针药组的垂直分、体重未出现差异(P＞0.05)。但在水平分和糖水消耗量上,电针组、针药组高于模型组、药物组(P＜0.05),电针组和针药组相当(P＞0.05),药物组与模型组相当(P＞0.05)。治疗7天后,额叶皮质5-HT1A受体mRNA和5-HT2A受体mRNA的表达各组间并无差异。海马5-TH2A受体mRNA表达下降,而5-TH1A受体mRNA表达上升。对于5-HT2A受体mRNA,电针组和针药组在中缝核、海马都有显著提高,而药物组在中缝核没有变化,在海马虽有提高但又低于电针组和针药组。电针组和针药组比较,电针组在中缝核和海马5-HT2A受体mRNA表达显著高于针药组。【结论】①针药结合治疗抑郁症临床疗效确切,优于单用SSRI类抗抑郁药,且起效速度快,以对HAMD抑郁量表的焦虑/躯体化因子分改善明显为特点;②针药结合可以提高抑郁症及其引起的睡眠障碍的疗效,在改善睡眠质量、入睡时间、睡眠时间、睡眠效率、日间功能障碍五项上均有优势;③针药结合治疗抑郁症的各个证型的疗效不同,肝郁脾虚组与心脾两虚组疗效相当,脾肾阳虚组疗效相对次之;④HAMD抑郁量表和中医辨证分型症状评分表来评价临床疗效时评分出现差异,故而具有中医辨证思维特点的量表以及疗效评价体系是一个重要研究方向;⑤在动物实验中,针药结合抗抑郁也表现出快速起效,以改善水平穿越活动和嗜糖水性为特点,且电针组和针药组起效相当;⑥电针和针药结合抗抑郁的快速起效作用可能是通过升高海马5-HT2A受体水平,降低5-HT1A受体水平,同时避免了激发中缝核的负反馈机制而起作用的。⑦考虑到电针和针药结合抗抑郁的快速起效作用相当,而药物并未起效,所以认为电针在快速起效中起了主要作用。更多还原

【Abstract】 [Objective] Observation of effect of acupuncture combined with SSRI treatment of depression and to explore the role of the characteristics of its rapid-onset of central 5-HT receptor mechanism.[Method]①92 cases of depression were randomly divided into groups with acupuncture combining SSRI antidepressants and sleep promoted medicine 50 cases (needle-group) and SSRI antidepressants group 42 cases (control group). Hamilton depression scale (HAMD), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI) and self-made TCM Syndromes Scale were used to be clinical evaluation scale.②The rat model of depression were randomly divided into drug group (fluoxetine), electro-acupuncture group, acupuncture medicine group, after 7 days treatment, Open-Field behavior assessment, experimental dessert consumption,and determination of raphe nucleus, hippocampus, frontal cortex of 5-TH1A receptor mRNA , 5-TH2A receptor mRNA expression by real-time RT PCR method.[Result]①After four weeks treatment, efficiency of both groups on HAMD, SDS , PSQI points of the difference was significant (P <0.01). HAMD after 2, 4 weeks treatment, the difference was significant (P <0.01). SDS score at the rate of reduction compared with a difference (P <0.05). The difference of five factors of PSQI in the two groups like sleep quality, falling sleep time, sleep time, sleep efficiency and day dysfunction were significant (P <0.01). But in sleep disorder, no difference (P> 0.05). Liver depression and spleen deficiency group and heart-spleen deficiency group had a considerable effect (P> 0.05), kidney-spleen yang deficiency group had a less effect (P <0.05).②After 7 days treatment on the rat model of depression, each group was lower than normal group (P <0.01) in behavioral score, weight, and dessert consumption. Model group, drug group, electro-acupuncture group and acupuncture combining medicine group were no difference in vertical score and body weight (P>0.05). However, at the level score and dessert consumption, electro-acupuncture group, acupuncture combining medicine group were higher than the model group and drug group (P <0.05), electro-acupuncture group and acupuncture combining medicine group are equivalency (P> 0.05), drug group and model group are equivalency (P> 0.05). After 7 days treatment, prefrontal cortex 5-HT1A receptor mRNA and 5-HT2A receptor mRNA expression there is no difference between the groups. Hippocampal 5-TH2A receptor mRNA decline, and 5-TH1A receptor mRNA increased. For the 5-HT2A receptor mRNA, electro-acupuncture group and acupuncture combining medicine group in raphe nucleus and hippocampus are significantly increased, while the drug group in the raphe nuclei did not change, although in the hippocampus improved but less than electro-acupuncture group and acupuncture combining medicine group. Electro-acupuncture group was significantly higher than acupuncture combining medicine group in the raphe nucleus and hippocampus of 5-HT2A receptor mRNA expression.[Conclusion]①Acupuncture combining medicine has clinical efficacy in the treatment of depression precisly, superior SSRI antidepressants, and the fast onset, HAMD depression scale on the anxiety / somatization factor scores improve significantly characterized;②With acupuncture combining medicine can improve sleep disturbance caused by depression, has advantages sleep quality, sleep time, sleep time, sleep efficiency and daytime dysfunction;③Acupuncture combining SSRI antidepressants on the treatment of liver depression and spleen deficiency depression effected better;④TCM syndromes symptom score table of Chinese medicine treatment methods Clinical Evaluation of sensitive and more accurate, it is worth further study;⑤At the level score and dessert consumption, electro-acupuncture group, acupuncture combining medicine group were higher than the model group and drug group, electro-acupuncture group and acupuncture combining medicine group are equivalency;⑥The rapid-onset of antidepressant in electro-acupuncture and acupuncture combining medicine may be through increased hippocampal 5-HT2A receptor levels, reducing the level of 5-HT1A receptors, while avoiding the excitation of raphe nuclei negative feedback mechanism works.⑦Taking into account the rapid-onset of antidepressant are equivalency between the electro-acupuncture and acupuncture combining medicine group, so that the electro-acupuncture played a major role.更多还原