针刺百会_足三里对抑郁症患者血清炎性细胞因子水平的影响_英文_.pdf

World Journal of Acupuncture-Moxibustion(WJAM),Vol.20,No.4,30th Dec.20101Clinical ResearchEffect of acupuncture at Bihu(百会 GV 20)and Zsnl(足三里 ST 36)on the level of serum inflammatory cytokines in patients with depression*针刺百会、足三里对抑郁症患者血清炎性细胞因子水平的影响*SUN Hua(孙 华)1 ZHAO Hui(赵 慧)2 ZHANG Jie(张 捷)3 BAO Fei(包 飞)1 WEI Jing(魏 镜)1 WANG Dao-hai(王道海)1 ZHANG Yun-xiang(张云祥)1 1.Department of TCM,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China；2.Institute of Basic Medical Sciences,Chinese Acadamy of Medical Sciences and School of Basic Medicine,Peking Union Medical College；3.Beijing Hospital of TCM（1.中国医学科学院北京协和医学院北京协和医院中医科,北京100730,中国；2.中国医学科学院基础医学研究所 北京协和医学院基础学院;3.北京中医医院）ABSTRACT Objective To investigate the immunologic mechanism of acupuncture at Bihu(百会 GV 20)and Zsnl(足三里 ST 36)for treatment of depression.Methods Eighty-four cases of depression patients were randomly divided into an electroacupuncture observation group(group A),an electroacupuncture control group(group B)and a medication control group(group C),28 cases in each group.Bihu(百会 GV 20)and Zsnl(足三里 ST 36)were used in the group A;Tichng(太冲 LR 3),Snynjio(三阴交 SP 6),Nigun(内关 PC 6)and Shnmn(神门 HT 7)were used in the group B;and the group C was treated with oral administration of Fluoxetine.The scores of Hamilton Depression Scale(HAMD)were tested and the level of serum interleukin 1(IL-1),interleukin 6(IL-6),and tumor necrosis factor (TNF-)were measured by Enzyme Linked Immunosorbent Assay（ELISA）before and after treatment.Results Their scores of HAMD were obviously decreased after treatment in three groups(all P0.01).In the group A,2 cases were cured,19 cases were markedly effective,5 cases were effective and 2 cases were failed.In the group B,16 cases were markedly effective,12 cases were effective.While in the group C,1 case was cured,17 cases were markedly effective,7 cases were effective and 3 cases were failed.The grade distribution of clinical effect showed that the effect of group A was better(P0.05).The levels of serum IL-1 and IL-6 in the three groups were obviously decreased after treatment(P0.05,P0.01),while there was no signifi cant difference between the level of serum TNF-before and after treatment.Conclusion The effect of electroacupuncture observation group is superior to those of electroacupuncture control group and medication control group.All of these three methods can clear the inflammatory cytokines such as IL-1 and IL-6 away and improve the symptoms of depression.*Supported by The Specifi c Chinese Medicine Project of Chinese Medical Science and Technology,The State Administration of Traditional Chinese Medicine:04-05 LP 10 This paper has won the Excellence of Academy Year in 2009,China Acupuncture and Moxibustion Association.First author:SUN Hua(1957-),female,chief physician.Research fi eld:treatment of cerebrovascular disease and depression with acupuncture and moxibustion.E-mail:This paper was fi rstly published in Zhongguo Zhenjiu(Chin Acup-Mox,Chin)in Chinese,2010,3 World Journal of Acupuncture-Moxibustion(WJAM),Vol.20,No.4,30th Dec.20102KEY WORDS Depression;Acupuncture Therapy;Point GV 20(Bihu);Point ST 36(Zsnl);Interleukin-1;Interleukin-6 摘 要 目的：探讨电针百会、足三里治疗抑郁症的免疫机制。方法：将84例患者随机分为电针观察组、电针对照组、药物对照组，每组28例。电针观察组穴取百会、足三里；电针对照组穴取太冲、三阴交、内关、神门；药物对照组给予百优解口服。在治疗前后分别用汉密尔顿抑郁量表（HAMD）评分，采用酶联免疫分析法（ELISA）检测患者血清中白细胞介素1（IL-1）、白细胞介素6（IL-6）、肿瘤细胞坏死因子-（TNF-）的水平。结果：与治疗前比较，各组患者治疗后HAMD评分均显著降低（均P0.01）。电针观察组痊愈2例，显效19例，有效5例，无效2例；电针对照组分别为0例、16例、12例、0例；药物对照组分别为1例、17例、7例、3例，临床疗效等级分布提示电针观察组有较好的疗效（P0.05）；3组患者血清IL-1、IL-6 水平均较治疗前显著降低(P0.05，P0.05),indicating comparability.METHODSEA observation group Selection of points:Bihu(百会 GV 20)and Zsnl(足三里 ST 36).Operation:after routine sterilization,Hwato brand sterile needle,0.30 mm40 mm,was used to puncture Bihu(百会 GV 20)World Journal of Acupuncture-Moxibustion(WJAM),Vol.20,No.4,30th Dec.20104transversely and manipulated with rotation technique.Another needle was inserted 3 mm lateral to Bihu(百会 GV 20)obliquely toward Bihu(百会 GV 20).After arrival of qi,Full-function Electric Pulsating Apparatus of Great Wall Brand(KWD-808)was used,3 Hz in frequency,continuous wave,tolerable intensity.Zsnl(足三里 ST 36)was punctured bilaterally and stimulated with electric pulsating apparatus.The needles were retained for 30 min.The treatment was given once daily for 5 days a week and free for 2 days in weekend.EA control groupSelection of points:Tichng(太冲 LR 3),Snynjio(三阴交 SP 6),Nigun(内关 PC 6)and Shnmn(神门 HT 7).Operation:after routine sterilization,Hwato brand sterile needle,0.30 mm40 mm,was used to puncture conventionally.After arrival of qi,Full-function Electric Pulsating Apparatus of Great Wall Brand(KWD-808)was used at Tichng(太冲 LR 3)and Snynjio(三阴交 SP 6),3 Hz in frequency,continuous wave,tolerable intensity.The needles were retained for 30 min.The treatment was given once daily for 5 days a week and free for 2 days in weekend.Medication control group Oral administration of Fluoxetine(Eli Lilly and Company,USA,20 mg each tablet),20 mg,once a day.The efficacy was observed after continuous treatment of 6 weeks among 3 groups.Indices and methods of detectionFor all the patients,from 8:00 am to 9:00 am,5 mL blood was collected from elbow vein and the serum was centrifuged with centrifuge at low temperature,4,2 000 r/min for 20 min.After packing separately,the sample was stored in freezing at-80ELISA was adopted to detect the levels of IL-1,IL-6 and TNF-in serum before treatment and at the endpoint of trial(the end of 6-week treatment)separately.Criteria of effi cacy judgmentHAMD of edition 24 items was adopted for the detection before treatment,after 2 and 4 weeks treatment as well as at the endpoint of trial(the end of 6-week treatment)separately and the statistical management was performed.Meanwhile,the effi cacy assessment of HAMD score reducing rate was applied.The score reducing rate=(total score before treatment total score after treatment)total score before treatment 100%,the result was expressed with percentage.Cured:HAMD score reducing rate 75%.Markedly effective:HAMD score reducing rate50%and 75%.Effective:HAMD score reducing rate25%and 50%.Failed:HAMD score reducing rate25%1.Statistical analysisAll the data were analyzed with SPSS 12.0 soft-ware.Measurement data was expressed with mean standard deviation(xs).ANOVA was adopted for HAMD score comparison.Independent-t test was used for the comparison of serology indices among groups.Paired t test was used for the intra-group comparison before and after treatment.Rank sum test was used for the effi cacy comparison between two samples.RESULTSComparison of HAMD total score at different time points among three groups(see Table 1)It was found in Table 1 that there were no statistical Table 1 Comparison of HAMD total score at different time pointsbefore and during treatment among three groups of depression patients (xs)GroupsPatientsBefore treatmentafter 2 week treatment after 4 week treatmentafter 6 week treatmentEA observation2822.143.65 17.503.451)2)12.963.781)2)10.042.271)EA control2820.863.37 17.503.471)2)13.892.941)2)10.043.521)Medication control2823.643.8421.184.401)16.634.051)11.824.481)Notes:compared with that before treatment in the same group,1)P0.01;compared with that in the same period in the medication control group,2)P0.05),indicating comparability.Compared with the value before treatment and after 2-week treatment,HADM total scores in EA observation group(t=11.01),EA control group(t=695)and medication control group (t=4.09)decreased significantly(all P0.01),of which,the value in either EA observation group(Z=-3.282)or EA control group(Z=-3.810)was lower than that in medication control group(both P0.01).The results after 4-week treatment were same as the values after 2-week treatment(all P0.01),of which,the result in either EA observation group(Z=-3.460)or EA control group(Z=-2.940)was lower than that in medication control group(both P0.01).There was no statistical signifi cant difference in HAMD score among 3 groups in the 6th week,suggesting that the therapies of 3 groups were all effective clinically,but the efficacy of electroacupuncture was obtained quite faster than that of medication.Additionally,compared with that before treatment,HAMD total score decreased significantly in 3 groups after treatment,indicating statistical significant differences(all P0.01)and suggesting that the therapies of 3 groups could be the effective approaches for the treatment of depression and applicable clinically.Effi cacy comparison among three groups(see Table 2)It was shown in Table 2,by paired rank sum test,Mann-Whitney analysis and efficacy assessment of HAMD score reducing rate,in comparison between EA observation group and medication control group,Z=-2.787,P0.05;in comparison between EA observation group and medication control group,Z=-1.422,P0.05;in comparison between EA observation group and EA control group,Z=-2.383,P0.05,suggesting that EA observation group obtained much better effi cacy as compared with either EA control group or medication control group.Comparison of IL-1,IL-6 and TNF-levels in serum before and after treatment among three groups(see Table 3)It was indicated in Table 3 that as compared with the value before treatment,IL-1 level in EA observation group(t=3.585),EA control group(t=3.960)and medication control group(t=4.520)decreased signifi cantly after treatment(all P0.01).After treatment,IL-6 level in medication control group(t=3.702)and EA control group(t=6.396)decreased significantly as compared with the value before treatment(both P0.01),and IL-6 level in EA observation decreased(t=2.627,P0.05).Moreover,there were no statistical differences in IL-1,IL-6 and TNF-levels after treatment in comparison Table 2 Comparison of effi cacy among three groups of depression patients Cases(%)GroupsPatientsCuredMarkedly effectiveEffectiveFailedEA observation 282(7.1)19(67.9)5(17.9)2(7.1)EA control 280(0)16(57.1)12(42.9)0(0)Medication control 281(3.6)17(60.7)7(25.0)3(10.7)Table 3 Comparison of IL-1,IL-6 and TNF-levels in serum before and after treatment among three groups of depression patients (xs,pg/mL)GroupsPatientsTimeIL-1IL-6TNF-EA observation 28Before treatmentAfter treatment 17.8234.449 11.0959.3542)14.3127.736 9.8525.2471)21.1368.835 18.92917.583EA control 28Before treatmentAfter treatment 19.8246.810 12.4877.8102)16.9595.921 8.8745.6912)21.4457.910 18.10123.544Medication control 28Before treatmentAfter treatment 20.2027.454 11.8136.6472)15.4429.575 8.2693.7872)23.42513.974 18.44218.751Notes:compared with that before treatment in the same group,1)P0.05,2)P0.05).DISCUSSIONDepression is the essential type of mental disorder which is the syndrome manifested chiefl y as obvious,persistent low mood.The incidence and attack rate of depression are quite high,which impacts seriously the physiological and psychological health and social communication of patients and damages obviously the ability of daily life activity.It is estimated through the global disease burden investigation that till 2020,just being the second to ischemic heart disease,depression will become the 2nd category disease to threaten the health of mankind,and increase disease burden.It will bring much more troubles to the people in the future 2.The early research3 showed that the depression patients were lower in tendency in immunologic function.But,the latest research emphasized on immune activation.It was discovered by Maes,et al4 and Kronfol5 that for the patient with serious depression,his/her plasma presented high expression of proteins in acute stage,such as haptoglobin(HPG),plasma ceruloplasmin(CER),antitrypsin(AT)and C-reactive protein(CRP),etc.,as well as low expression of proteins in acute stage,such as transferring(TRF),retinol-binding protein(RBP)and low albumin(ALB).All of these suggested that depression was relevant with infection possibly.Maes6 proposed that chronic depression was relevant with chronic inflammatory reactive infection and further pointed out that the chronic infl ammatory state of depression was probably induced by the cytokine secreted from cyclic monocyte and macrophage.Proinflammatory cytonines(IL-1,IL-6 and TNF-)can induce infl ammatory reaction7.Ur,et al8 believed that probably,the increase of some cytokines(such as IL-1 and IL-6 etc.)promoted the activity of corticotrophin-releasing hormone(CRH),and eventually resulted in hyperactivity of hypothalamus-pituitary-adrenal axis(HPA)and further induced depression.The literature9 reported that during the occurrence of depression,IL-1 could better activate HPA,and the cytokines,like IL-6 and TNF-brought their actions into play when IL-1 was not existed.Fluoxetine is 5-HT re-intake inhibitor.By the strong inhibition of presynaptic 5-HT re-intake pump,the drug increases synaptic cleft 5-HT concentration,promotes the transmission of 5-HT neurotransmitter and brings anti-depression into play.Its clinical efficacy is good.But,still a part of patients suffer from adverse reactions,such as nausea,vomiting,constipation,profuse sweating,headache and sexual dysfunction etc.after medication.Being a kind of treatment approach,by holistic adjustment of qi and blood in Zang-fu,meridians and collaterals,acupuncture is capable to relieve mental and physical symptoms and recover the body to be normal.The research on the mechanism of modern acupoint function proved that Bihu(百会 GV 20)acted positively on nerve system,endocrinal system and immune system10,which provided the theoretic evidence on the treatment of depression.Moreover,it was proved by clinical observation that this acupoint was effective on depression11.The authors believed that the imbalance of 5-HT receptor function was one of the major reasons of depression and EA at Bihu(百会 GV 20)and Zsnl(足三里 ST 36)could regulate it obviously12,which provided the reliable practical basis of acupoint selection in treatment of depression.Chinese medicine believes that depression is in the category of melancholia and is a kind of emotional disorder like mental depression due to disturbance of qi activity and loss of control in the brain induced by internal injury of seven emotional factors.The occurrence of the disease is relevant with qi,blood,phlegm and stagnation,with the heart,liver,spleen and kidney involved.The acupoints are selected mainly by syndrome differentiation of depression in acupuncture treatment,from the Heart,Liver and Spleen Meridians as well as the Governor Vessel.By synthesized a large amount reports and clinical experiences of the authors,Bihu(百会 GV 20)was selected as the chief acupoint and Zsnl(足三里 ST 36)was the assistant one.Bihu(百会 GV 20)is the key acupoint of the Governor Vessel,located on the vertex of head World Journal of Acupuncture-Moxibustion(WJAM),Vol.20,No.4,30th Dec.20107and is“the palace of clear mind in the head”,acting on opening orifice and regaining consciousness.The Governor Vessel runs in the spine,upwardly,enters the bra