| 1 ObjectiveThis project used the method of meta analysis to observe and compare the effectiveness and safety differences between electroacupuncture(EA)and western medicine.Besides,a randomized,controlled,paralled clinical trial was designed to assess the effectiveness and safety of EA treatment.An animal experiment was also designed to determine the exact mechanisms of EA treatment for PSD,providing scientific proofs for the effectiveness of EA treating with PSD.2 MethodsMeta analysis: Electronic searches were conducted in VIP,CNKI,Wan-Fang,CMB,EMBASE,Pubmed and Cochrane library.All the RCTs of EA treatment for PSD were collected and selected.Then,RCTs of EA treatment for PSD compared with western medicines were meta analyzed to find out the efficacy differences of EA and western medicines.Clinical research: PSD patients were randomizedly allocated into EA group and control group.For EA group,EA treatment was combined with oral fluoxetine(20mg/d).2/20 Hz frequency and dilatational wave were used for EA treatment.Acupoints of DU20,LR3,SP6 and BL18 were selected.Each treatment session lasted for 30 min.It was conducted once a day,5 times a week.One treatment course consisted of 10 sessions,and all the enrolled patients were treated for 2 courses.For control group,only oral fluoxetine(20mg/d)was applied to the patients for 1 month.Hamilton Depression Scale(HAMD),Depression Scale of traditional Chinese medicine(Depression Scale of TCM)were scored to assess the anti-depressive effects of EA.NIHSS was used to evaluate the improvement of neurological function.Adverse events(AEs)were recorded to assess the safety of treatment in both groups.Animal experiment: 40 male SD rats were randomly divided to control group,PSD group,EA group and EA+Cyclopamine group.PSD models were established by middle cerebral artery occlusion(MCAO)surgery and chronic unpredictable mild stress(CUMS)procedures.2/20 Hz frequency and dilatational wave were used for EA treatment.Acupoints of DU20,LR3,SP6 and BL18 were selected.Each treatment session lasted for 30 min.It was conducted once a day,5 times a week.The treatment lasted for 1 month.With the dosage of 0.2μg/g,the intraperitoneal injection of signaling blocker cyclopamine was done every two days for 1 month.The sucrose preference ratio and locomotor activity test were observed.The pathological morphology of rat hippocampal neurons were tested by Nissl staining.Serum BDNF,5-HT and NE were tested by Elisa.WB was applied to measure Bcl-2,Bax,Shh and Gli1 protein expression of rat hippocampus.RT-pcr was taken to measure Shh and Gli1 gene expression of rat hippocampus.3 ResultsMeta analysis: 19 RCTs were searched and selected to be included into the meta analysis.Of these,there were 848 people in the EA group with 758 people in the controlled group,and all the controlled groups were treated by anti-depressants.Scores of HAMD,SDS,NIHSS,MESSS,CNS,BI,ADL,FIM,FMA and TESS were assessed.The scores of Jadad quality evaluation were relatively low.All the included studies used HAMD to evaluate depression severity and the improvement 4 weeks,6 weeks and 8weeks after treatment.Of these,13 studies recorded HAMD scores 4 weeks after treatment,meta analysis revealed that HAMD scores reduced significantly in EA group compared with anti-depressants group(P<0.01)with a rather high heterogeneity.4studies recorded HAMD scores 6 weeks after treatment,meta analysis revealed that HAMD scores didn’t reduce significantly in EA group compared with anti-depressants group(P>0.05).5 studies recorded HAMD scores 8 weeks after treatment,meta analysis revealed that HAMD scores didn’t reduce significantly in EA group compared with anti-depressants group(P>0.05).It was also indicated that AEs were much less in EA group than those in anti-depressants group with no significant heterogeneity.Clinical research: At the end of the first treatment course,scores of HAMD(P<0.05),Depression Scale of TCM(P<0.01)and NIHSS(P<0.01)were significantly lower in EA group than those in control group.Besides,scores of HAMD(P<0.01),Depression Scale of TCM(P<0.01)and NIHSS(P<0.01)in both groups were significantly lower than those assessed before treatment.At the end of the second treatment course,scores of Depression Scale of TCM(P<0.05)and NIHSS(P<0.01)were significantly lower in EA group than those in control group.Besides,scores of HAMD(P<0.05),Depression Scale of TCM and NIHSS(P<0.01)in EA group were significantly lower than those assessed at the end of the first treatment course.Scores of HAMD(P<0.01),Depression Scale of TCM and NIHSS(P<0.01)in control group were also significantly lower than those assessed at the end of the first treatment course.During treatment,AEs in EA group were less than those in control group.Animal experiment: Compared PSD group with control group,both sucrose preference ratio(P<0.01)and locomotor counts(P<0.01)decreased significantly,hippocampal neurons reduced significantly(P<0.01),protein of Bax increased significantly(P<0.01),protein of Bcl-2 and Bcl-2/Bax decreased significantly(P<0.01),protein of Shh(P<0.05)and Gli1(P<0.01)reduced significantly,m RNA of Gli1(P<0.01)also reduced significantly.serum BDNF decreased(P<0.01),serum 5-HT reduced significantly(P<0.01),serum NE decreased(P>0.05).Compared EA group with PSD group,both sucrose preference ratio(P<0.01)and locomotor counts(P<0.01)increased significantly,hippocampal neurons increased significantly(P<0.01),protein of Bax decreased significantly(P<0.01),protein of Bcl-2 and Bcl-2/Bax increased significantly(P<0.01),protein of Shh(P<0.05)and Gli1(P<0.01)increased significantly,serum BDNF increased(P<0.01),both serum 5-HT and NE increased significantly(P<0.01).Compared EA+Cyc group with EA group,both sucrose preference ratio(P<0.01)and locomotor counts(P>0.05)decreased,hippocampal neurons decreased significantly(P<0.01),protein of Gli1(P<0.01)reduced significantly,serum BDNF decreased(P>0.05),serum 5-HT reduced significantly(P<0.05),serum NE decreased(P>0.05).4 ConclusionsMeta analysis: EA treatment is effective for PSD and is not less effective than western medicine.EA is better than western medicine in safety.Clinical research: EA treatment is effective for alleviating depression severity and improving nerve function of PSD patients.Compared with single western medicine treatment,EA treatment has the advantage of ideal effectiveness and better safety.Animal experiment: EA can improve depressive behaviors of PSD rats by increasing BDNF,Bcl-2,ratio of Bcl-2/Bax,decreasing Bax and up-regulating monoamine neurotransmitters 5-HT and NE,which is associated with activating Shh-Gli1 signaling pathway. |
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