A Randomized Controlled Study On Acupuncture Treatment Of Regulating Liver And Spirit For Depression And The Postreceptor Signal Transduction Mechanism

Objective:To observe the clinical effects of acupuncture treatment of regulating liver and spirit for depression and explore the mechanism on postreceptor signal transduction pathway.Methods:1.275 cases were randomized into the following groups:acupuncture group, prozac group and sham-acupuncture group, and the effects were evaluated by the HAMD scales, the SDS scales, the WHOQOL-BREF scales, the improvement scales of symptoms of Traditional Chinese Medicine and the SERS sacles.2. Adult male Sprague-Dawley rats (180-200g) were used in the present experiment. Animals were divided randomly into four groups:the control group, the model group, the acupuncture group and medicine treatment group. There were 8 rats in each group. The chronic mild stress model of depression was induced by various kinds of stress for 21 days. In the EA group, two stainless acupuncture needles (0.28 mm outer diameter) were bilaterally inserted 5mm into the LI4 and LR3. EA treatment and stress were simultaneously made, and electrical stimulation were from a medical EA apparatus (Model G6805-2, Shanghai, China). The stimulation parameters were a frequency of 2 and 20 Hz, alternatively, and the intensity strong enough to only elicit slight twitches of the lower limbs. The EA treatment was made once per day for 3 weeks and performed for fifteen minutes. Rats in the medicine treatment group was treated with fluoxetin (1.8 mg/kg/d, ig, set according to the dosage for patients) for 3 weeks. Changes of weight, open-field behavior, hippocampal neurons and expression of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were observed in the study.Results:Clinical study:The gross effective rate was higher and the hamd scale score was better in the acupuncture group than that in the prozac group and sham-acupuncture group, while SERS score was better in the both acupuncture groups than that in the prozac group, with no severe side-effects documented for acupuncture.Experimental study:1. Changes of weight:the increased extent of the weight in the model group, EA treatment group and medicine treatment group were lower than that in the control group. Moreover, it was higher in the model group than in the medicine group. EA treatment and antidepressant did not show significant improvement on the weight of depression rats.2. Changes of open field behavior:the behavior (horizontal and vertical motion)of the depression rats decreased significantly following stress, and EA treatment can effectively improve it, which is better than that of the antidepressant.3. Morphological changes of hippocampus neurons:In the depression rats, neurons were dispersedly distributed in the dentate gyrus (DG), which showed edema, atrophy and denaturation. Both EA and antidepressant treatment can obviously improve the morphological abnormality in the hippocampal neurons.4. Expression of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus:CREB and BDNF positive neurons in the depression rats were scatteredly distributed in the DG, and the intensity of the reaction products was obvious weak, and the number of positive neurons was remarkably decreased. In the EA and antidepressant group, both CREB and BDNF positive neurons were regularly distributed, and the expression of CREB and BDNF in the hippocampus up-regulate obviously. Conclusions:1. Acupuncture treatment of regulating liver and spirit, the core of which is the regulation of liver and Qi, was effective in treating depression and could be spread and applied as a standardization Rx.2. Acupuncture treatment of regulating liver and spirit showed a curative effect on depression after treatment for one month, and showed more obviously curative effect with increase in period of treatment, which was comparable to prozac.3. Acupuncture treatment of regulating liver and spirit was safe for the treatment of depression and the side effects were inferior to prozac.4. Acupuncture could improve significantly changes of the behavior, pathological changes of neurons in the hippocampus, and expressions of CREB and BDNF in the hippocampus in rats, therefore cAMP-CREB-BDNF postreceptor signal transduction pathway is an important approach and target of acupuncture in treating depression.