Dissertation
Dissertation > Medicine, health > Neurology and psychiatry > Psychiatry > Affective psychosis

Acupuncture and fluoxetine on differences of the forced swim stress rats and effects of JNK signal pathway

Author BaoWuYe
Tutor TuZuo
School Beijing University of Traditional Chinese Medicine
Course Acupuncture and Massage
Keywords acupuncture Fluoxetine forced swimming depression JNK signalpathway differences
CLC R749.4
Type PhD thesis
Year 2014
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Depression is a prevailing mental disorder featured with longterm low mood, slow thinking and reduced spiritual movements. Depression leads to a high mortality. The disease is seriously harmful to the physical and mental health as well as the quality of life. Moreover, depression can bring huge burden to the family on the facets of the spirit and economy. And it is also can give rise to the financial burden to the society.The pathogenesis of depression is related with multiple factors as heredity, neuroendocrine system problem, psychology, social effects, etc. Owing to its role in depression pathogenisis and treatment, celluar signal transduction pathways attract increasing attention.A host of literatures have confirmed therapeutic effects of acupuncture for depression. Its mechanism is about the functional disorders of neuroendocrine system and immune system. The reports of depression rats’intracerebral cell signaling pathways which effected by acupuncture is increasing. However, there is rarely papers about pointing out the differences between acupuncture and antidepressant drugs.In the current research, we applied forced swimming method to induce psychopharmacological desperation model in rats. Based on observations of behavioral indice, JNK pathway factors related to depression-stress response, pro-inflammatory cytokines and HSP70, we are aiming to figure out anti-depression effectiveness of acupuncture and Fluoxetin with JNK signaling transduction pathway inhibitor SP600125, as well as the differences in JNK pathway modulations between acupuncture and Fluoxetin.Methods1Grouping48SD rats which were chosen familiar with open field test and sucrose consumption test and their weight is170±10g, then they were randomely divided using the random number table into the following groups:nomal group, normal+SP600125(SP for shot below) group, model group, model±SP group, acupuncture group, acupuncture group+SP group, fluoxetine group, fluoxetine+SP group,6rats each group.2Modeling methods This research choose the forced swimming model to imitate the despair of depression patients.Rats were placed in one aquarium with plenty of24±1℃water, and they were forced swimming for15min. After24h they were again forced swimming for6min. we took the records of the time which their stay still in4min. Using this records to evaluate the behavioristics.3Intervention technique No intervention in normal group. Normal+SP group, giving intraperitoneal injection of SP600125. Model+SP group, giving intraperitoneal injection of SP600125before modeling methods30min. Acupuncture group, needling" Baihui acupoint" and "Yintang acupoint" for20min before modeling methods. Acupuncture group+SP group, the same as acupuncture group of acupoints, methods and needling time, only difference is SP i. p. before acupuncture. Fluoxetine group, giving gavage before modeling methods with1.8mg/kg which is dissolved in distilled water. Fluoxetine+SP group, same as the fluoxetine group, the only difference is SP i. p.30min earlier than gavage.4Index and methods Testing the contents of IL-1, IL-6, TNF-α, HSP70in rats’hippocampus with ELISA. Research the content of MKK4, MKK7, JNK, p-JNK, c-jun in hippocampus with Western blot. The genetic expression of caspace-3in hippocampus were detected with RT-PCR.Results1Alterations in behavioral indiceThere is no difference between normal group and model+SP group on the stay still time of forced swimming rats (P>0.05); compared with normal group, the stay still time of forced swimming significantly increased in model group (P <0.01); compared with model group, the stay still time is decreased in model group+SP group, acupuncture group, acupuncture+SP group, fluoxetine group and fluoxetine+SP group (P<0.05, P<0.01, P<0.01, P<0.01, P<0.01);there is no statistically significant in model+SP group, acupuncture group, acupuncture+SP group, fluoxetine group and fluoxetine+SP group (P>0.05)2IL-1,IL-6,TNF-α levels in serum and hippocampusThe tendency of each group is parallel. Normal group compared with model group, the contents of IL-1,IL-6,TNF-α in serum and hippocampus are similar (P>0.05); compared with normal group, a remarkable increase of IL-1, IL-6,TNF-α in serum and hippocampus can be seen in model group, model+SP group, acupuncture group, acupuncture+SP group, fluoxetine group, fluoxetine+SP group (all P<0.01); compared with model group, the significant reduction of IL-1,IL-6,TNF-α can be spotted in model+SP group, acupuncture group, acupuncture+SP group, fluoxetine group, fluoxetine+SP group(all P<0.01); there are statistical differences among model+SP group, acupuncture group, acupuncture+SP group, fluoxetine group, fluoxetine+SP group (all P<0.01), IL-1, IL-6,TNF-α levels in Fluoxetine group are lower than those in acupuncture group.(p<0.01)3MKK4, MKK7levels in hippocampusNormal group compared with normal+SP group, there is no obvious difference of contents of MKK4, MKK7in hippocampus (P>0.05); compared with normal group, the contents of MKK4.MKK7increase significantly in model group (all P<0.01) compared with model group, there are apparently reductions of MKK4.MKK7in hippocampus in fluoxetine+SP group (P<0.05), there is a negative trend of MKK4.MKK7in hippocampus in model+SP group, acupuncture group, acupuncture+SP group, at the same time, the difference has no statistical significance (all P>0.05); remarkable difference can be seen between acupuncture group and fluoxetine group (P<0.05)4JNK, p-JNK levels in hippocampusThere is no difference of content of JNK in hippocampus in each group (均P>0.05)The expression level of p-JNK in hippocampus, there is no difference between normal group and normal+SP group (P>0.05); compared with normal group, the content of p-JNK in hippocampus has significantly increased in model group (P <0.01); compared with model group, there are significantly decrease of p-JNK in hippocampus in model+SP group, acupuncture group, acupuncture+SP group, fluoxetine group, fluoxetine+SP group (all P<0.01); no difference between acupuncture group and fluoxetine group (P>0.05)5C-jun level in hippocampusThere is no difference of c-jun levels in hippocampus between normal group and normal+SP group (P>0.05); the content of c-jun in hippocampus increased significantly in model group comparing with normal group (P<0.01); compared with model group, c-jun level in hippocampus decreased significantly in model+SP group, acupuncture group, acupuncture+SP group, fluoxetine group, fluoxetine+SP group (p<0.05, P<0.05, P<0.01, P<0.01, P<0.01); C-jun levels in fluoxetine group is significantly lower than that in acupuncture group (P<0.01)6Gene expression level of Caspase-3in hippocampus There is no difference of caspase-3expression level in hippocampus between normal group and normal+SP group (P>0.05); compared with normal group, the caspase-3expression level in hippocampus of rats increased significantly in model group (p<0.01); compared with model group, remarkable reductions of caspase-3expression level are found in hippocampus in model+SP group, acupuncture group, acupuncture+SP group, fluoxetine group, fluoxetine+SP group (all p<0.01); Capase-3levels in fluoxetine group is significantly lower than that in acupuncture group (p<0.01)7HSP70level in serum and hippocampusThere is no difference of contents of HSP70in serum and hippocampus in rats between normal group and normal+SP group (P>0.05); compared with normal group, the significant increase of HSP70in serum and hippocampus can be seen in model group (all p<0.01); compared with model group, there are reduction of HSP70in serum and hippocampus can be spotted in model+SP group, acupuncture group, acupuncture+SP group, fluoxetine group, fluoxetine+SP group (all p<O.01); there is apparent difference of HSP70in serum and hippocampus between acupuncture group and fluoxetine group (p<0.01)Conclusions1The forced swimming stress lead to despair condition in rats, lengthen the swimming stay still time. These behavioral changes can be improved by acupuncture and fluoxetine.2The forced swimming stress lead to increased secretion of IL-1β, IL-6, TNF-a in rats’serum and hippocampus. The excessive secretion of IL-1β,IL-6,TNF-α can be decreased by acupuncture and fluoxetine on rats.3The forced swimming stress activate JNK signaling pathway in rats’ hippocampus, increase the level of p-JNK. This elevated level of p-JNK in hippocampus can be reversed by acupuncture and fluoxetine, JNK signaling pathway can be inhibited effectively in rats’cerebrum.4The forced swimming stress lead to increased transcription level of c-jun and caspase-3in rats’hippocampus. Both acupuncture and Fluoxetine can significantly reduce the transcripton of nuclear transcripts c-jun and Capase-3.5The forced swimming stress lead to HSP70increase in serum and hippocampus. Acupuncture and fluoxetine compromised HSP70expression to normal level.6SP600125exerts no influence on behaviors, pro-inflammatory cytokines, prominent factors in JNK pathway and HSP70in normal rat. However, in forced swimming stress model rats, it counld improve behavioral deficits, compromise secretions of pro-inflammtory cytokines, inhibit p-JNK in hippocampus and decrease expressino of c-jun, Capase-3and hippocampal HSP70.7No differences is found between acupuncture and Fluoxetine in behavioral deficit improvement. Fluoxetine is superior to acupuncture in modulating serum and hipplcampal pro-inflammatory cytokines, c-jun, Capase-3gene and HSP70levels.

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