【作者】 段冬梅；

【导师】 图娅；

【作者基本信息】 北京中医药大学 ， 针灸推拿学， 2008， 博士

【摘要】 电针抗抑郁的临床疗效及机制研究研究背景随着现代社会工作和生活节奏不断加快,竞争等应激事件日益增加,人们承受的心理压力也日益增大。无论是发达国家还是发展中的中国,心理健康问题越来越严重,其中以抑郁症(depression)的发病率上升最为明显。抑郁症是目前临床上常见的、难治性的疾病,是由各种原因引起的以抑郁心境自我体验为中心的临床症状群或状态,严重危害人们的心身健康。针灸治疗抑郁症由来已久,以其疗效确实,无明显副作用为特点。因此如何发挥针灸治疗抑郁症的优势,揭示针灸治疗抑郁症的机理,从而进一步提高抑郁症的治疗效果,是亟待深入探索的问题。目的1.对照研究三种方案即电针、百优解、电针+百优解治疗轻、中度抑郁症的临床疗效、起效时间、安全性及预后。2.对志愿者进行1H-MRS检查,比较健康成人脑海马、前额叶代谢物质的相对浓度,确定其分布特点,为抑郁症的脑MRS研究提供参照依据。3.对抑郁症患者脑海马、前额叶的NAA, Cho, Cr物质进行1H-MRS定量分析,探讨治疗前后抑郁症患者脑内代谢物质的变化特点,为抑郁症神经生化基础研究提供线索,为临床诊断提供依据。4.利用磁共振成像和波谱分析,整体、动态地观察三种方案干预状态下抑郁症患者脑功能活动的各项指标及其与抑郁量表评价的相互关联性;寻找抑郁症的临床常见中医证型磁共振检查可能存在的差异,为电针广泛应用于临床治疗抑郁症提供理论准备。方法1.将75例轻、中度抑郁症患者采用实用型随机分为A组(百优解组)、B组(电针组)、C组(百优解+电针组),各组间在年龄与性别构成上无统计学差异。采用HAMD抑郁量表、SDS抑郁自评量表评定临床疗效,起效时间、有效率和复发率,TESS副反应量表评定药物不良反应。2.健康志愿者20例,采用GE EXCITE II Signa 3.OT磁共振系统,PROBE-J序列进行单体素采集,感兴趣区(ROI)分别置于左、右两侧海马和额叶。比较男女间NAA/Cho、NAA/ Cr和Cho/ Cr值的差异。3.三组抑郁症患者,采用GEEXCITE II Signa 3.OT磁共振系统,PROBE-J序列进行单体素采集,感兴趣区分别置于左、右两侧海马和额叶。比较3组与正常对照组间以及治疗前后NAA/Cho、NAA/ Cr和Cho/ Cr值的差异;比较中医4型与正常对照组间以及治疗前后NAA/Cho、NAA/ Cr和Cho/ Cr值的差异。结果1.百优解+电针组临床控制率29.17%及总有效率91.67%明显优于电针组(临床控制率21.74%,总有效率82.61%),以及百优解组(临床控制率17.39%,总有效率78.26%),差异有显著性意义(P<0.05)。2.三组患者治疗后HAMD、SDS均分数较治疗前明显下降,治疗前后自身比较差异有非常显著性的意义(P<0.01)。治疗后百优解+电针组与电针组、百优解组比较差异有显著性意义(P<0.05)。说明3种治疗方法均有一定改善抑郁症患者临床症状的作用,但百优解+电针组明显优于电针组及百优解组。3.百优解+电针组在治疗2周后HAMD评分较治疗前的差异有显著性意义(P<0.05)。电针组从治疗4周后HAMD评分较治疗前的差异有显著性意义(P<0.05),百优解组从治疗5周后HAMD评分较治疗前的差异有显著性意义(P<0.05)。说明百优解+电针组起效最快,百优解组起效最慢。4.电针组、百优解+电针组的躯体症状、睡眠障碍因子分较治疗前的差异有极显著性意义(P<0.01)。百优解组、百优解+电针组的抑郁迟滞因子分较治疗前的差异有显著性意义(P<0.05)。电针在改善躯体症状、睡眠障碍方面有优势,百优解在改善抑郁迟滞方面有优势。5.百优解+电针组的药物副作用明显较百优解组轻,严重度评分明显逐渐减少,说明百优解+电针组的综合治疗显著减轻了百优解的副反应。百优解+电针组复发率较百优解组明显减少,差异有显著性意义(P<0.05)。6.按中医辩证分组疗效显示,肝郁气滞型临床控制率最高,疗效最显著,肝肾阴虚型疗效较差,差异有非常显著性意义(P<0.01)。7.健康志愿者男、女性别之间的两侧额叶、海马NAA/Cho、NAA/ Cr和Cho/ Cr值比较不存在统计学差异(P>0.05)。8.治疗前三组患者双侧海马的NAA/Cr值较对照组明显减低,双侧额叶的Cho/ Cr值较对照组明显增高,差异有显著性意义(P<0.05)。治疗后电针组双侧海马、百优解+电针组右侧海马的NAA/Cr值较治疗前增高,差异在统计学上有显著性意义(P<0.05),百优解+电针组左海马的NAA/Cr值较治疗前明显增高,差异有非常显著性意义(P<0.01);治疗后百优解组、电针组双侧额叶的Cho/ Cr值较治疗前减低,差异有显著性意义(P<0.05)。百优解+电针组双侧额叶的Cho/ Cr值较治疗前明显减低,差异有非常显著性意义(P<0.01)。9.治疗前肝郁脾虚型、心脾两虚型、肝肾阴虚型抑郁症双侧海马NAA/ Cr、双侧前额叶Cho/ Cr与对照组的差异有显著性意义(P<0.05);而肝郁气滞型双侧海马NAA/ Cr、双侧前额叶Cho/ Cr与对照组比较,其差异在统计学上无显著性意义。说明治疗前肝郁气滞型(实证)抑郁症与对照组1H-MRS检测的代谢物比值之间没有显著性差异,而其他三型抑郁症(虚证)与对照组之间有显著性差异,其结果与肝郁气滞型抑郁症患者病例数相对少,病程相对短,病情相对较轻有一定关系,1H-MRS检测的代谢物比值是否能区别抑郁症中医分型的实证与虚证,仍需大样本进一步证实。治疗后心脾两虚型、肝郁脾虚型双侧海马NAA/ Cr、双侧前额叶Cho/ Cr与治疗前的差异有显著性意义(P<0.05);而治疗后肝肾阴虚型双侧海马NAA/ Cr、双侧前额叶Cho/ Cr与治疗前比较,其差异无显著性意义。说明治疗后肝郁脾虚型、心脾两虚型效果显著,与对照组之间没有显著性差异,而肝肾阴虚型疗效不佳,与对照组的差异仍有显著性差异。其结果与肝肾阴虚型抑郁症患者病程相对长,病情相对较重有一定关系,仍需大样本进一步证实。结论1.电针能明显改善抑郁症的躯体症状,起效快,减轻百优解的不良反应,百优解+电针治疗轻、中度抑郁症疗效好,不良反应少,复发率低,是值得临床推广的较优化治疗方案。2.1H-MRS能较准确的显示NAA, Cho, Cr等代谢物的波谱,是了解脑内生化信息的一种有重要价值的方法。正常成人额叶、海马间的代谢物浓度存在差异,这些差异反映了相应部位组织学结构的不同。3.抑郁症患者两侧额叶、海马与正常成人相应部位的代谢物浓度存在差异,从本质上揭示了抑郁症的发生机制。三种方案干预前后抑郁症患者脑功能活动的各项指标及其与抑郁量表评价的一致性,临床常见中医证型磁共振检查亦存在着差异,为抑郁症临床诊断及疗效评价提供了一种新的探索手段。更多还原

【Abstract】 BackgroundIn the fast paced modern society, people are bearing much psychological pressure. In both developed and developing countries including China, mental health problems are becoming more and more serious. Among which, the high incidence of depression should be pay more attention to. Depression is a popular and refractory disease, which seriously endangers people’s physical and mental health. It has a long history of acupuncture treatment for depression, which characterized by its significant effectiveness and no side effects. Therefore, it is an urgent task for us to show its advantages and discover its mechanisms and then improve it.Object1. Find out the different effect, the onset time, the security and the prognosis of there different plans for depression, which are EA, fluoxetine and EA+ fluoxetine.2. To take the 1H‐MRS exam of the consistence of the metabolic matters in hippocampus and prefrontal lobe of the healthy volunteers and definite the matters’location. This can Provides reference basis for depression research.3. To take the quantitative analysis of the NAA, Cho, Cr of the hippocampus and prefrontal lobe of the depression patients. To explore the changes between treatment and after treatment of the depression patients. This can provides evidence for the clinical treatment.4. Use MRI and MRS methods to evaluate the three different treatment methods holistically and dynamically. To find out the relationship between these iconography indexes and the depression scales. By doing this we can combine the different type of the TCM differentiation according to the syndromes with the image methods in order to provide theoretic basis for EA to depression. Method1. 75 minor and mild depression patients were divided into three groups, which are A (fluoxetine group), B (EA group), C (fluoxetine+ EA group). There is no significant difference in those three groups in the age and sex. Use HAMD, SDS to evaluate the clinical effective rate, the onset time and the recurernce rate; while use TESS scale to evaluate the untoward effect.2. Use PROBE‐J sequence at GE EXCITE II Signa 3.OT MRI system on Single Voxel of the ROI of bilateral hippocampus and frontal lobe of 20 healthy volunteers. Compare differences of the NAA/Cho, NAA/ Cr and Cho/ Cr between men and wemen.3. Use PROBE‐J sequence at GE EXCITE II Signa 3.OT MRI system on Single Voxel of the ROI of each lateral hippocampus and frontal lobe depression patients of the three groups. Compare the differences of NAA/Cho, NAA/ Cr and Cho/ Cr between the healthy volunteers and the patients and also the patients before treatment and after treatment. In addition, compare the differences of NAA/Cho, NAA/ Cr and Cho/ Cr between the different TCM syndrome differentiation types.Result1. The control rate of C (fluoxetine+ EA group) is 29.17% and the effective rate is 91.67% which is much significantly higher than the A (fluoxetine group) with the control rate of 17.39% and the effective rate of 78.26%, B (EA group) with the control rate of 21.74%and the effective rate of 82.61%(P<0.05).2. Compared with the average before treatment, the HAMD and SDS average of the patients in the three groups significantly decreased after treatmen(tP<0.01). And the C (fluoxetine+ EA group) showed a significant difference with the A (fluoxetine group) and B (EA group) (P<0.05).This may suggest the preferable effectiveness of the C (fluoxetine+ EA group) than the other two groups.3. The significant difference(P<0.05) between before treatment and after treatment of C (fluoxetine+ EA group) started from the second week. While it happened to B (EA group) (P<0.05) from the fourth week and the A (fluoxetine group), the fifth week. This indicates that fluoxetine with EA together function most quickly and the fluoxetine only function most slowly.4. There were significant differences between before treatment and after treatment in somatization syndromes and the somnipathy factor scores of the B (EA group) and C (fluoxetine+ EA group) (P<0.01). There were significant differences between before treatment and after treatment in retarded factor scores of the B (EA group) and C (fluoxetine+ EA group)(P<0.05). This may indicate that EA is more effective in improving the somatization syndromes and he somnipathy while the fluoxetine is more effective in retarded depression.5. The side effect of the C (fluoxetine+ EA group) was much less than the A (fluoxetine group), which indicate that fluoxetine with EA together can alleviate the side effect of the fluoxetine only. The recurernce rateof the C (fluoxetine+ EA group) is significantly decreased than A (fluoxetine group) (P<0.05).6. The effective rate of Liver‐depression is significantly higher than the hepatic and renal yin deficiency type depression.(P<0.01).7. There were no significant differences between the men and women in NAA/Cho, NAA/ Cr and Cho/ Cr in each lateral hippocampus and frontal lobe.8. There were a significant decrease of the NAA/Cr in bilateral hippocampus and a significant increase of the Cho/ Cr of the bilateral frontal lobe of the depression patients in the three groups before treatment(P<0.05).The NAA/Cr in bilateral hippocampus of B (EA group) and the NAA/Cr of the right hippocampus of C (fluoxetine+ EA group) increased significantly(P<0.05),the NAA/Cr of the left hippocampus of C (fluoxetine+ EA group) increased very significantly(P<0.01). The Cho/ Cr of the bilateral frontal lobe of A(fluoxetine group) and B (EA group) decreased significantly after treatment(P<0.05). The Cho/ Cr of the bilateral frontal lobe of C (fluoxetine+ EA group) decreased very significantly after treatment(P<0.01)。9.There were significant differences in NAA/ Cr of bilateral hippocampus and Cho/ Cr of bilateral frontal lobe between Liver‐depression and Spleen‐deficiency type, Deficiency of both Heart and Spleen type and hepatic and renal yin deficiency type depression patients and healthy volunteers (P<0.05);While there were no significant differences in NAA/ Cr of bilateral hippocampus and Cho/ Cr of bilateral frontal lobe between Liver Stagnation type depression patients and healthy volunteers. The Liver Stagnation type depression patients is less than the other three groups and their course of disease is respectively shorter and patient’s condition is better than the other three types. This may suggest that the different TCM syndrome differentiation type may relate to their metabolism. This result needs further study.There were significant differences in NAA/ Cr of bilateral hippocampus and Cho/ Cr of bilateral frontal lobe between Liver‐depression and Spleen‐deficiency type and Deficiency of both Heart and Spleen type depression patients and healthy volunteers after treatment(P<0.05); While there were no significant differences in NAA/ Cr of bilateral hippocampus and Cho/ Cr of bilateral frontal lobe in hepatic and renal yin deficiency type depression patients between before treatment and after treatment. This may indicate that the treatment is more effective to the Liver‐depression and Spleen‐deficiency type, Deficiency of both Heart and Spleen type and Liver Stagnation type than to hepatic and renal yin deficiency type depression patients. This may because the long course of disease and severe patient’s condition. This result needs further study.Conclusion1. EA can alleviate the somatization of the depression patients and the side effects of the fluoxetine, EA with fluoxetine together is a prominent treatment for depression for its small side effect and recurernce rate.2. 1H‐MRS can reflect the spectrum of NAA, Cho and Cr accurately,so it is a valuable method to detect the biochemistry changes in brain. There is different in the density of the metabolite in frontal lobe and hippocampus of common adults, which may reflect their structural differences.3. There is difference between depression patients and common people in the density of the metabolite in frontal lobe and hippocampus, which may relate to the nosogenesis of depression. The changes of those scales and MRI index before and after those three treatment and their relation between different TCM syndrome differentiation type would provide new method to explore the treatment and evaluation of depression.更多还原