| In modern society, depression is a mental illness with high prevalence, harmfulness, and high morbidity. Significant lasting low mood is the main features of depression, and clinical manifestations are depressed mood, reduced interest, spiritual movement hysteresis, few words, accompanied by self-accusation, etc. When it goes serious it can lead to suicide. The world large epidemiological survey found that depression was the fourth disabling disease and lifelong rate of depression is between 3% ans 5%. It estimated that by 2020, depression will be the second disabling disease just behind ischemic heart disease, which is seriously harmful to humanbeings. It is a huge burden of the society.At present, treatment of depression is mainly dependent on drugs. Treatment of single target is obtain sure curative effect, but it still can't get rid of side effects and lower patient compliance. Acupuncture has curative effect of depression, and it can regulate the whole body. It can improve patient's depression syndromes, cognitive disorders, and life quality. The effect is continuous, comprehensive, effective but without side effects. In recent years, inceasingly researches on antidepression treatment mechanism of acupuncture found that it is an overall treatment, and can maintain existence of brain neurons to protect the brain neurons.Therefore, we choose Ras-MEK-ERK and Ras-MKK-JNK signaling pathways related with existence and apoptosis of neurons to observe the changes. Choose a solitary rat model with chronic stress for experiment to simulate depression process of humans. Use hand needle, EA to puncture into "Baihui-yintang", "Neiguan", and paroxitine as intervention to the model rats. Observe movements,sucrose intake,weight and expression changes of monoamine neural transmitter of rats to evaluate the establishment of the model. Research on the treatment mechinism of acupuncture antidepression in physiological and pathological state and differences between acupuncture and drug treatment, between hand needle and EA,in order to explore the antidepression treatment mechanism of acupuncture.Methods and results1.Establish a solitary rat model with chronic stress,then use weight,sucrose intake and open-field tests to evaluate the model.Before 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 of model group decreased (P<0.05). Compared with model group, needle group,EA group,paroxitine group can increase the rats'weight (P<0.01); and paroxitine group can increase the rats'sucrose intake (P<0.05); needle group can increase the rats'crossing number (P<0.01), needle group,EA group,paroxitine group can increase the rats' rear number (P<0.01,P<0.01,P<0.05). Compared with control group, rats in control+needle group showed no significant change in behavior tests.2. Use ELISA test to detect monoamine neural transmitter (5-HT\NE\DA) levels in serum of solitary depression model rats with chronic stress, and see the changes after the intervention treatments. Results:â‘ 5-HT:Compared with control group,5-HT in model group,hand needle group,EA group and paroxitine group decreased (P<.05); compared with model group, hand needle group,EA group and paroxitine group increased (P<.05); there was no difference among hand needle group,EA group and paroxitine group.â‘¡DA: compared with control group, DA in model group decreased (P<.05); compared with model group, hand needle group,EA group and paroxitine group increased (P<0.05); there was no difference among hand needle group,EA group and paroxitine group.â‘¢NE:Compared with control group, NE in model group,hand needle group,EA group and paroxitine group decreased(P<0.05); compared with model group, hand needle group,EA group and paroxitine group increased (P<0.05); there was no difference among hand needle group,EA group and paroxitine group. Compared with control group, rats in control+needle group showed no significant change of 5-HT, NE and DA.3. Western blot test Ras-MEK-ERK signal passway (ERK1/2, p-ERK1/2) in hippocampus and prefrontal cortex. Results:â‘ Compared with control group, ERK1 in hippocampus and prefrontal cortex of model group has no change; ERK2 in hippocampus decreased (P<0.01).â‘¢ompared with control group, p-ERK1 in hippocampus and prefrontal cortex of model group obviously decreased (P<0.01). Compared with model group in hippocampus, hand needle group,EA group obviously increased (P<0.01),and paroxitine group increased (P<0.05); EA group was obviously better than paroxitine group (P<0.01), hand needle group was better than paroxitine group (P<0.05). Compared with model group in prefrontal cortex, hand needle group,EA group obviously increased (P<0.01); compared with paroxitine group, hand needle group,EA group obviously increased (P<0.01).â‘¢Compared with control group, p-ERK2 in hippocampus and prefrontal cortex of model group obviously decreased (P<0.01). Compared with model group in hippocampus, hand needle group,EA group and paroxitine group obviously increased (P<0.01),no difference among them. Compared with model group in prefrontal cortex, hand needle group,EA group obviously increased (P<0.01),and paroxitine group increased (P<0.05); compared with paroxitine group, hand needle group,EA group obviously increased (P<0.01). Compared with control group, rats in control+needle group showed no significant change of p-ERK1/2.4. Western blot test CREB in hippocampus and prefrontal cortex. Results:â‘ Compared with control group, CREB in hippocampus of model group obviously decreased(P<0.05), and in prefrontal cortex no changes.â‘¡Compared with control group, p-CREB in hippocampus and prefrontal cortex of model group obviously decreased (P<0.01). Compared with model group in hippocampus, hand needle group,EA group and paroxitine group obviously increased (P<0.01);and compared with hand needle group, EA group,paroxitine group obviously increased (P<0.05, P<0.01). Compared with control group, rats in control+needle group showed no significant change of p-CREB.5. Western blot test BDNF in hippocampus and prefrontal cortex. Results:Compared with control group, BDNF in hippocampus and prefrontal cortex of model group obviously decreased (P<0.01). In hippocampus:compared with model group, hand needle group,EA group obviously increased (P<0.01),and paroxitine group increased(P<0.05); compared with hand needle group, EA group and proxitine group not have enough advantages (P<0.01),and EA group is better than paroxitine group (P<0.05). In prefrontal cortex: compared with model group, hand needle group,EA group and paroxitine group obviously increased (P<0.01); compared with hand needle group, EA group and proxitine group not have enough advantages (P<0.01). Compared with control group, rats in control+needle group showed no significant change of BDNF.6. Western blot test BAD/Bcl-2 tatio in hippocampus and prefrontal cortex. Results:â‘ In hippocampus:compared with control group, number in model group increased (P<0.05) compared with model group, number in hand needle group,EA group and paroxitine group decreased (P<0.05),and no difference among the three treatment groups.â‘¡In prefrontal cortex:compared with control group, number in model group increased (P<0.01); compared with model group, hand needle group and paroxitine group decreased (P<0.01),and no difference among them. Compared with control group, rats in control+needle group showed no significant change of BAD/Bcl-2 tatio.7. Western blot test Ras-MKK-JNK signal passway (JNK, p-JNK, c-Jun, Caspase-3) in hippocampus. Results:â‘ There is no difference between model group and control group about expression of JNK in hippocampus.â‘¡Compared with control group, p-JNK in model group increased (P<0.01); compared with model group, p-JNK in hand needle group decreased (P<0.05).â‘¢Compared with control group, c-Jun in model group increased (P<0.01).â‘£Compared with control group,Caspase-3 in model group increased (P<0.01); compared with model group,hand needle group,EA group and paroxitine group decreased (P<0.01), while hand needle group and EA group are better than paroxitine group (P<0.01).Compared with control group, rats in control+needle group showed no significant change of JNK,p-JNK,c-Jun protein in statistics.Compared with control group, rats in control+needle group showed significant change of Caspase-3 (P<0.05);but compared with model group, rats in control+needle group showed significant change of Caspase-3 protein (P<0.01).Conclusions1.Chronic stress induced rat model, can mimic humans'depressive symptoms.Chronic stress could cause the rats to move less, suppress body weight gain of rats, decreasing of sucrose intake and expression of 5-HT\NE\DA in serum, inhibite Ras-MKK-JNK signaling pathway, active Ras-MKK-JNK signaling pathway, increase the ratio of BAD/Bcl-2 to inncrease neuron apoptosis.2. The results showed that Acupuncture in physiological condition, there were no significant changes about ethology, amine neurotransmitter in serum, phosphorylation of ERK and JNK. So we can infer that acupuncture maybe hasn't the function to change the normal balance of body.3. All three interventions can improve behavior performance. Acupuncture is better than paroxetine in detective behavior, but paroxetine is better than acupuncture in rewarding reaction.4. All three interventions can reverse depletion state of amine neurotransmitter in serum of rats, but three were no statistically difference among them.5. Compared with paroxetine, acupuncture can markedly improve phosphorylation level of ERK 1/2 protein kinase, stimulate Ras-MAPK/ERK pathway, and expand protein expression of BDNF, to protect the neurons.6. Compared with paroxetine, acupuncture may significantly adjust phosphorylation level of JNK protein kinase, restrain Ras-MKK-JNK pathway, and reduce protein expression of caspase-3, to reduceneuron apoptosis.7. Both Acupuncture and paroxetine can reduce the ratio of BAD/Bcl-2 to protect the neurons.8. According to the result, in pathologic state, both acupuncture and paroxetine can adjust phosphorylation level (p-ERK1/2, p-JNK) of MAPK signaling pathways, which caused the expantion of cells effect proteins showed significant diffence eventually.9. According to the result, we infer that these chages above maybe have relationship with the basic mechanism of acupuncture antidepression treatment. It maybe the resean for the advantages that acupuncture has early effection, decreasing toxic, improve patients' overall state in clinic. |
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