The Clinical And Signal Transduction Pathways Research Of Treating Generalized Anxiety Disorder With Electroacupuncture From "Heart And Gallbladder"

Objective1. Analysis the clinical efficacy and safety of electric acupuncture on anxiety based on systematic review of literatures.2. Observe the clinical efficacy, safety and effect on quality of life of electric acupuncture on generalized anxiety disorder via diagnosis and treatment from the heart and gallbladder.3. Explore the potential mechanism of electric acupuncture on anxiety from MAPK/ERK signal pathway.Methods1. Systematic reviews:The randomized control literature of clinical studies was collected to treat anxiety disorder by electric acupuncture, CBM (1979～), VIP (1989～), Wanfang digital journal groups (1998～), PubMed (1966～), EMbase (1980～) and Cochrane Library. All the search time was by January2011, the back issues data bank in the library of Guangzhou University of Chinese Medicine was manually searched. The risk and quality of bias were assessed on the experiments adopted according to Cochrane Handbook5.0, and RevMan5.0.24was adopted for the statistical analysis.2. Clinical research:64patients met the inclusion criteria were divided into treatment group and control group. Using electric acupuncture and selected Neiguan (two sides), Yanglingquan (two sides), adopted G-6805Ⅱ type electro-acupuncture instrument following needling response, with density wave at a frequency of lOHz and amplitude of3V, treated3times a week and30min for each time with interval more than24h, a total of6w in treatment in treatment group. Adopt paroxetine (China and the United States (GSK) Pharmaceutical Co., Ltd, Tianjin) oral dose of20mg/d for6w in control group. Evaluate curative effect using HAMA and SAS before treatment, at2w,4w,6w of treatment and at lm after treatment in two groups. Perform described analysis, chi square test, t test, multivariate variance analysis and repeated measuring data with SPSS19.0software.3. Experimental study:63adult female SD rats with weighted of150+10g was randomly divided into blank group, model group, EA group, medicine group, PD98059(ERK specific blocker) group, PD98059combined with EA group and PD98059combined with medicine group, with9rats in each group. Blank group remained untreated. Model group received conditioned electric shock for21days to construct anxiety model. EA group performed EA treatment following modeling. Using G-6805Ⅱ type electric acupuncture apparatus density wave at a frequency of2Hz and amplitude of3V, we acupunctured points of Neiguan and Yanglingquan in rats alternatively for15min at each time, once daily. Medicine group were intragastric administered to medicine once daily after modeling (paroxetine were administered at1.8mg/kg). PD98059group was performed intracerebroventricular injection of PD98059(ERK specific blocker). PD98059combined with EA group was performed intragastric administration of paroxetine following at3h after intracerebroventricular injection of PD98059on successful modeling (as indicated above). PD98059combined with medicine group was performed intragastric administration of paroxetine after3h of intracerebroventricular injection of PD98059. Intervention in each group lasted for21days. Observe rats weight and changes in elevated plus-maze behavior before intervention and at7d,14d and21d after intervention. Detect the phospho-ERK, immunofluorescence expression and Western Blot expression of hippocampus in rats after experiment.Results1.System evaluationInto eight randomized controlled trials, including769patients in the local area of the Meta analysis treat anxiety:two groups of efficient difference was statistically significant (OR=0.95,95%CI (0.55,1.64)], show that in the local area and western medicine therapy anxiety both quite efficient; Two groups of recovery rate is statistically significant differences [OR=1.53,95%CI (1.07,2.20)], shows that the recovery in the local area in treat anxiety rates are higher than western medicine. Two groups of HAMA score difference was statistically significant [WMD=0.61,95%CI (1.96,1.98)]; In the local area and western medicine that treat anxiety of HAMA score both quite. Two groups of SAS score difference was statistically significant [WMD=0.35,95%CI (1.73,1.03)]; In the local area and western medicine that treat anxiety SAS score both quite. Grade evidence for very low quality evaluation (very low), suggests that this system evaluation any effect is very uncertain estimate of, in the future, need more high quality clinical studies to confirm that.2. Clinical research2.1Baseline comparison:two groups of patients, gender, TCM syndrome type, age, duration and HAMA, SAS, SF-36score more, no statistically significant (P=0.802,0.979,0.905,0.895>0.05) show that the general information between groups are homogeneous, balance and comparability.2.2Treatment two weeks, two groups of patients HAMA and SAS scale integration which is significantly less before treatment, group is between statistical significance. HAMA scale two factors mental anxiety factor and the body sex anxiety factors, the body sex anxiety factor score more significant, significant difference (P<0.05), and mental anxiety factor score no obvious difference between the two groups.2.3In the treatment of4,6weeks, two groups of patients HAMA and SAS scale integration is still decline gradually, mental anxiety factor and body sex anxiety factor downward trend of the obvious, compare between groups were not significant, the two groups of efficient and overall effect after statistics processing, the difference was not statistically significant (P>0.05).2.4The treatment ended January follow-up, two groups of patients HAMA and SAS scale integration when it was over, more treatment slow upward trend, the group is back in the local area between group by group less than drugs, with significant difference (P<0.01)2.5In the local area and drug therapy can all can improve SF-36survival quality scale of physiological functions (PF), and physical pain (BP), overall health (GH), energy (VT), social function (SF), emotional functions (RE), mental health (MH) dimension, both no obvious difference (P=0.090>0.05). But in electricity for physiological mechanism (RP) is superior to the improvement of the drug treatment (P=0.00<0.05).2.6The treatment group (15.6%) of the recurrence rate lower than those of the control group (21.8%), and adverse reaction is less than control.3. experimental research3.1The weight gain of rats in model group was lower than blank group. After intervention of electric acupuncture and medicine for21days, the weight in rat model of anxiety was close to blank group, while there was no obvious effect of intervention by PD98059combined with EA and PD98059combined with medicine for21days on weight of rat model of anxiety (P>0.05). Furthermore, the weight gain of rats in EA group was higher than medicine group at7days and there was no significant difference with medicine group at14days and21days, while there was no significant difference in PD98059combined with EA and PD98059combined with medicine at7days,14days and21days (P>0.05).3.2Both EA and medicine could change anxiety-like behavior in rat model of anxiety so that it was close to normal. However, the effect of PD98059combined with EA and PD98059combined with medicine on anxiety-like behavior of model rat was not obvious after21days of intervention (P>0.05). There was no difference between the two kinds of intervention.3.3Both immunofluorescence and Western blot analysis revealed that both EA and medicine could reduce phosphated ERK (p-ERK) of hippocampus in anxiety model, and there was no significant difference between two interventions (P>0.05); their antianxiety effect could be blocked by PD98059.Conelusions1.1. Systematic reviews revealed the differences in effective rate, HAMA scores and SAS scores between EA group and medicine group were equivalent. The cure rate in EA group was higher than medicine group and the adverse effect in EA group was lower than medicine group, but GRADE's Rating Quality of Evidence was very low which remained to need high-quality clinical research to provide more reliable evidences.2. Both the electric acupuncture treating generalized anxiety disorders on heart and gallbladders and medicinal treatment (paroxetine) were effective and the overall efficacies were equivalent. The degree of electric acupuncture on somatization symptom was larger than medical treatment at2w; while the effect of electro-acupuncture therapy was lasting than medical treatment with reduced recurrence rate after treatment. The electric acupuncture was safety in treating anxiety based on heart and gallbladder and had lower adverse effect than paroxetine, which could be promoted to be applied as complementary and alternative therapies for medical therapy in clinical.3.. Electric acupuncture could significantly improve weight and ethology in rat model of anxiety and down regulate p-ERK expression in hippocampus and the effect could be blocked by PD98059(ERK specific blocker). There was no significant difference compared with medicine group. It suggested that MAPK/ERK signal transduetion pathway was one of critical action ways for anti-anxiety by electric acupuncture.