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不同电针对抑郁症胃肠道躯体症状的临床观察及实验研究
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摘要
目的
     1观察针刺治疗抑郁症胃肠道躯体症状的临床有效性,并比较不同电针的作用效果。探讨音乐电针是否为抑郁症的临床治疗提供了一种切实可行的方法。
     2观察脉冲电针和音乐电针百会穴、印堂穴对抑郁症模型大鼠行为学、小肠推进运动、脑肠肽含量、海马及结肠黏膜超微结构变化,从脑肠轴的角度分析电针对抑郁模型大鼠的作用效应及机制。
     方法
     1临床研究
     选择66例肝郁脾虚型轻中度抑郁症患者,随机分为音乐组和脉冲组,应用汉密尔顿抑郁量表及中医证候量表在治疗前(0周)、治疗2周、4周、6周末(或中止时)对患者进行评定,对主要疗效指标采用PP分析方法进行分析,评价不同电针抗抑郁的临床效果和对抑郁症胃肠道躯体症状的改善程度。
     2实验研究
     选取符合条件SD大鼠60只按体重随机分为空白组、模型组、百优解组、脉冲电针组、音乐电针组共5组,每组12只。采用慢性不可预见的温和刺激结合孤养方法制备抑郁模型。百优解组应激且孤养21天,将百优解以生理盐水配制成1mg/mL,按照2mg/kg体重,于每日应激刺激1小时前灌胃给药,每天1次,共21天。脉冲电针组于造模同时行脉冲电针干预,选取“百会”、“印堂”穴,频率2Hz,电流强度为0.6mA,留针20min,每日1次,连续针刺21d。音乐电针组接ZJ-12H音乐电针治疗仪,音乐选取抗抑郁处方,其他与脉冲电针组处理一致。于实验前后进行行为学观察,包括体重、糖水实验和开野实验;行为学观察结束后,检测大鼠下丘脑和结肠黏膜中GAS、NPY、CGRP、β-EP含量、小肠推进运动情况、海马神经元及结肠黏膜超微结构。
     结果
     临床研究
     1脉冲组和音乐组在治疗2、4、6周时的疗效差异无统计学意义,两组治疗结束时的总有效率亦无统计学意义(P>0.05)。
     2脉冲组和音乐组治疗对HAMD评分总分均有明显的改善。脉冲组第4周末,音乐组第2周末时与治疗前比较有显著性差异(P<0.05);脉冲组第6周末,音乐组第4周末时与治疗前比较有极显著性差异(P<0.01)。
     3两组在治疗4周末和6周末时,音乐组与脉冲组比较HAMD总分评分有显著性差异(P<0.05),说明音乐组在改善HAMD总分评分方面要优于脉冲组。
     4治疗6周末时,脉冲组抑郁情绪、入睡困难、睡眠不深、早醒、精神性焦虑、躯体性焦虑、胃肠道症状、全身症状以及体重减轻的评分在疗后与疗前比较均有显著性差异(P<0.05);音乐组抑郁情绪与胃肠道症状评分疗后与疗前比较有极显著性差异(P<0.01),入睡困难、睡眠不深、早醒、精神性焦虑、躯体性焦虑、全身症状以及体重减轻评分疗后与疗前比较均有显著性差异(P<0.05)。音乐组与脉冲组在入睡困难、睡眠不深、早醒以及胃肠道症状评分上有显著性差异(P<0.05),而抑郁情绪、精神性焦虑、躯体性焦虑、全身症状以及体重减轻评分上无显著性差异(P>0.05),说明音乐组在改善抑郁症患者入睡困难、睡眠不深、早醒以及胃肠道症状方面要优于脉冲组。
     5脉冲组与音乐组中医证候评分总分在治疗第4周末时与治疗前比较有显著性差异(P<0.05),治疗第6周末时与治疗前比较有极显著性差异(P<0.01),说明两组治疗对中医证候评分总分均有明显的改善。在治疗4周末和6周末时,音乐组与脉冲组比较中医证候评分总分评分有显著性差异(P<0.05),说明音乐组在改善中医证候评分方面要优于脉冲组。
     6治疗6周末时,中医证候评分胃肠道相关症状减分情况疗后与疗前比较,脉冲组忧愁善感、食欲下降、胁肋胀痛、腹胀、腹痛、便溏评分疗后与疗前比较均有显著性差异(P<0.05);音乐组忧愁善感、腹痛、便溏评分疗后与疗前比较有显著性差异(P<0.05)、食欲下降、胁肋胀痛、腹胀均有极显著性差异(P<0.01)。音乐组与脉冲组比较,食欲下降、腹胀、腹痛、便溏评分有显著性差异(P<0.05),而忧愁善感、胁肋胀痛评分无显著性差异(P>0.05),说明音乐组在改善抑郁症患者食欲下降、腹胀、腹痛、便溏方面要优于脉冲组。
     7两组疗前及疗后血常规、尿常规及心电图检查均无异常改变,也无血压升高现象;针刺时均未出现严重不良事件,针刺部分输穴,可出现晕针、皮下出血及血肿反应,采取相应措施可消除不良反应。
     实验研究
     1实验前各组大鼠行为表现均无统计学差异。实验结束后,模型组大鼠体重、糖水消耗量减少,均与空白组大鼠有极显著性差异(P<0.01);而旷场实验水平穿越格数与直立次数显著低于空白组大鼠(P<0.05).
     2实验21天后,开野试验水平运动和垂直运动次数,与模型组比较,药物组有极显著性差异(P<0.01),脉冲组和音乐组有著性差异(P<0.05)。药物组、脉冲组与音乐组各治疗组间比较无显著差异(P>0.05)。
     3实验14天后,脉冲组、音乐组大鼠体重增加显著高于模型组(P<0.05)。实验21天后,脉冲组、音乐组、药物组大鼠体重增加显著高于模型组(P<0.05),药物组与脉冲组比较无显著性差异(P>0.05);音乐组与药物组比较有显著差异,音乐组与脉冲组比较有显著性差异(P<0.05)。
     4实验第21天,药物组、脉冲组与音乐组糖水摄入量明显高于模型组(P<0.05)。药物组与两电针组比较均无显著差异(P>0.05)。
     5实验21天后,药物组、脉冲组、音乐组结肠粘膜GAS含量显著增加而NPY与CGRP含量显著降低;下丘脑GAS、NPY、CGRP含量显著增加,与模型组比较差异均有统计学意义(P<0.05)。音乐组在调整大鼠结肠黏膜GAS、CGRP含量方面要优于脉冲组,在调整大鼠下丘脑GAS、NPY含量方面要优于脉冲组(P<0.05)。
     6实验21天后,药物组、脉冲组、音乐组下丘脑β-EP含量显著增加,与模型组比较差异均有统计学意义(P<0.05);结肠黏膜β-EP含量显著降低,与模型组比较差异均有统计学意义(P<0.05);音乐组与脉冲组比较无显著性差异(P>0.05)。
     7实验21天后,药物组、脉冲组、音乐组与模型组比较小肠碳末推进率显著增加(P<0.05),音乐组在改善抑郁模型大鼠小肠碳末推进率上优于脉冲组(P<0.05)。
     结论
     1脉冲电针和音乐电针治疗均可显著改善肝郁脾虚型中轻度抑郁症患者的HAMD评分及中医证候评分;音乐电针在改善抑郁症患者的睡眠情况及典型胃肠道症状等方面有较为突出的作用优势,可以更加显著提高睡眠质量,更加明显地改善本病患者因肝郁脾虚而导致的食欲下降、腹胀、腹痛、便溏等症状。
     2慢性应激抑郁大鼠模型造模成功,不仅出现行为学方面的改变,结肠黏膜与下丘脑的兴奋性激素与抑制性激素水平处于一种紊乱的状态,小肠推进率降低,海马出现病理学改变。
     3电针治疗能够达到阳性对照药物百忧解的治疗作用。
     4音乐电针治疗在对慢性应激抑郁模型大鼠的抑郁状态下脑—肠轴的多个环节进行整合的作用效果要优于脉冲电针。
Objective
     1Pulse electro-acupuncture treatment compared with musical electro-acupuncture in the clinic trials to investigate the effectiveness of depression with somatic symptoms of gastrointestinal tract, To investigate whether music electro-acupuncture is a advantageous method.
     2To observe the effect of pulse electro-acupuncture and musical electro-acupuncture of "Baihui"(GV20)and"Yintang"onbehaviorobservation,small intestinalpropulsion rate,brain-gut peptide levels and mortorphological changes of rat hippocampal neurons in depression model rats so as to provide experimental evidence for acupuncture treatment of gastrointestinal symptoms relatingto depression while comparingthe effect of pulse electro-acupuncture with musical electro-acupuncture.
     Methods
     1The66Patients were divided into2groups,one group accepted musical electro-acupuncture treatment,another pulse electro-acupuncture treatment.HAMI) and Chinese Medical Syndrome scales have been applied in the evaluation before and after the treatment.
     2Sixty SD rats were randomly divided into control.model.Prozac. Pulse electro-acupuncture and musical electro-acupuncture groups,with12rats in each group.Depression modal was established by chronic mild stimulation combined with isolated raising.For rats of the Prozac group were treated by gavaga of Prozac.once daily for21days.The rats of thePulse electro-acupuncture group."Baihui"(GV20) and "Yintang"(EX-HN3) were punctured and stimulated by pulse electro-acupuncture, once daily for21days. While the rats of theMusical electro-acupuncture group were punctured the same acupoints and stimulated by musical electro-acupuncture.Therat'sbodyweight.open-fieldtest,andrelativevolumeof sucrose-intake wererecorded one day before and during experiments.After the behavior observation,G AS,NPY,CGRP and β-EP in the rats'colonic mucosa tissues and hypothalamus were detected by Radiommunoassay or Elise detection method.Small intestinal propulsion rate were recorded. Whilethe ultra structure of the hippocampus and colonic mucosa tissues were observed by Flection Microscope.
     Results
     Clinical research
     1camparing pulse group with musicalgroup, there was no significant difference of curative effect at the end of2th,4th,6th week,while no significant difference of overall resultis at the end of treatment(P>0.05).
     2The HAMD score were significantly improved in both pulse group and music group. the improvement presented at4week in pulse group,while2week in music group (P<0.05) significant improvement presented at6week in pulse group,while4week in music group (P<0.01)
     3The HAMD score of music group was much lower than the pulse group at4,6week music group (P<0.05)
     4At the end of6week,the score of depression, difficulty falling asleep, poor sleep quality, wake early, Mental anxiety, somatic anxiety, gastrointestinal symptoms, systemic symptom and weight reduction in both musical and pulse group changed significantly camparing with prior treatment (P<0.05). Significant improvement of difficulty falling asleep, poor sleep quality, wake early and gastrointestinal symptoms presented in musical group camparing with pulese group (P<0.05)
     5The score of Chinese Medical Syndrome decreased Significantly at the end of4,6week (P<0.05),and musical group was better than pulse group (P<0.05)
     6the score of depression, decreased appetite, distending pain in hypochondrium, abdominal distension, abdominal pain and loose stools in both musical and pulse group changed significantly camparing with prior treatment (P<0.05). Significant improvement of decreased appetite, abdominal distension, abdominal pain and loose stools presented in musical group camparing with pulese group (P<0.05)
     7There were no serious adverse events during acupuncture,some slight adverse reaction was easy to eliminate by corresponding measures.
     experimental research
     1Before the experiment,there is no diffence among these groups. At the end of the experiment, there are different. Compared with control group rats,body weight and sucrose intake of model group obviousely decreased (P<0.01),and crossing numbers, rearing times of model group decreased (P<0.05).
     2Compared with model group, crossing numbers and rearing times of pulse group,musical group and Prozac group decreased (P<0.05)
     3Compared with model group,pulse group,musical group can increase the rats' weight at the end of14day(P<0.05);Compared with model group,pulse group,musical group and Prozac group can increase the rats' weight (P<0.05). there was no significant change between Prozac group and pulse group(P>0.05); Compared with Prozac group and pulse group,musical group can increase the rats' weight (P<0.05).
     4Compared with model group,pulse group,musical group and Prozac group can increase the rats' sucrose intake (P<0.05), there was no difference among pulse group,musical group and Prozac group (P>0.05)
     5Compared with model group, the level ofGAS in colonic mucosa tissues and GAS,NPY,CGRP in hypothalamus tissues were increased significantly in musical group Prozac group and pulse group, while the level of NPY and CGRP in colonic mucosa tissues was reduced obviously (P<0.05). The music group was superior to the pulse group in adjusting the GAS, CGRP level of rat colonic mucosa tissues and the GAS,NPY level of hypothalamus tissues (P<0.05)
     6Compared with model group, the level of β-HP in hypothalamus tissues was increased significantly, the level of β-HP in colonic mucosa tissues was reduced obviously in musical group. Prozac group and pulse group(P<0.05)
     7Compared with model group,pulse group,musical group and Prozac group can increase the rats' small intestinal propulsion rate (P<0.05), musical group was supurior than pulse group and Prozac group (P<0.05)
     Conclusion
     1Both pulse electro-acupuncture and musical electro-acupuncture can improve symptoms of depression of Liver stagnation and spleen deficiency syndrome,musical electro-acupuncture is better than pulse electro-acupuncture.
     2Animal model of chronic stress was established successlully.Chronie stress could change rats 'behavior, upsetexcitingand inhibitinggastrointestinal hormone levelsand bring mortorphological changes of rat hippocampal neurons.
     3Hffect of electroacupuncture treatment can achieve positive control drug Prozac.
     4Hlcctro-acupuncture improved the gastrointestinal dysfunction after depression by adjusting the unbalance of the exciting and inhibiting gastrointestinal hormonelevels in colonic mucosa to influence on the brain gut axiswith the musical electro-acupuncture much more better.
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