電針對(duì)慢性應(yīng)激抑郁大鼠腦海馬磷酸二酯酶-4亞型表達(dá)的影響
發(fā)布時(shí)間：2018-08-11 20:04
【摘要】：抑郁癥是一種綜合癥狀的情感障礙性精神疾病,其特征為情緒上的長(zhǎng)期低落。其有較高概率的發(fā)病、致殘和自殺比例,并有情緒低落、焦慮、精神活動(dòng)受損、食欲下降和失眠等特點(diǎn)。因而成為一種極大損害人類健康的疾病。據(jù)世界衛(wèi)生組織WHO公開的數(shù)據(jù)統(tǒng)計(jì)顯示,抑郁癥被列為全球上高居第四位的疾病。全球抑郁癥的平均發(fā)病率保守估計(jì)約為11%,預(yù)計(jì)到2020年,即五年內(nèi),將成為僅次于心臟病的第二大疾病隱患。在中國(guó),抑郁癥發(fā)病率約為3%～5%,目前有超過2600余萬人因抑郁癥飽受困擾。最近的流行病學(xué)調(diào)查表明,抑郁癥的終生患病率可達(dá)到為16%,排名在中國(guó)疾病負(fù)擔(dān)第二高的疾病。目前尚缺少特異性的方法在診斷學(xué)上為抑郁提供完美的解決方案。治療方法以西藥的治療及電休克療法為主。針刺療法對(duì)治療抑郁癥的治療在安全性、有效性上都有很好的表現(xiàn),且與西醫(yī)抗抑郁藥相比,針刺擁有起效迅速、毒副作用相對(duì)極小、費(fèi)用相比較明顯低廉等一系列優(yōu)勢(shì)。針刺治療抑郁的作用機(jī)制已有大量的研究成果,但還未能完全闡明其起效的靶點(diǎn)及全部通路,尚需開展進(jìn)一步的研究。目的本研究通過電針對(duì)慢性應(yīng)激抑郁模型大鼠行為學(xué)觀察結(jié)果的影響,并綜合運(yùn)用分子生物學(xué)方法進(jìn)一步探討電針治療抑郁癥的機(jī)制,試圖闡明電針對(duì)治療抑郁癥潛在靶標(biāo)PDE4A、PDE4D表達(dá)的影響。方法1.動(dòng)物分組用隨機(jī)方法將動(dòng)物分成四組,每組8只,分組分別為:空白組、模型對(duì)照組、藥物對(duì)照組、電針治療組。各組大鼠在實(shí)驗(yàn)前喂養(yǎng)一周,以適應(yīng)環(huán)境。然后開始慢性應(yīng)激刺激和不同干預(yù),空白組大鼠依然用不分籠群養(yǎng)模式,其余組大鼠每籠1只孤養(yǎng)方式�？瞻捉M與其余各組大鼠飼養(yǎng)于隔離的不同飼養(yǎng)室。2.造模方法采用慢性應(yīng)激模型結(jié)合孤養(yǎng),參考文獻(xiàn)方法,進(jìn)行慢性應(yīng)激郁癥大鼠模型的制備。造模動(dòng)物模型對(duì)照組、藥物對(duì)照組、電針治療組孤養(yǎng),接受21天7種不同的應(yīng)激刺激,包括冷水游泳、禁水、晝夜顛倒、禁食、夾尾、束縛、潮濕環(huán)境,每日隨機(jī)安排一種刺激,每種刺激平均3次。3.處理方法:空白組:在正常飼養(yǎng)條件下21天,采用非孤養(yǎng)模式,期間不予應(yīng)激刺激;模型對(duì)照組..慢性應(yīng)激造模21天,并在21天內(nèi)每日進(jìn)行與電針組等同的束縛干預(yù),時(shí)間長(zhǎng)度相同,強(qiáng)度同等;藥物對(duì)照組:慢性應(yīng)激加孤養(yǎng),每日配藥,按1mg/1ml的比例將百憂解以蒸餾水配制,按照2mg/kg體重,灌胃途徑給藥,給藥后1h應(yīng)激造模,每天一次,共21天;電針治療組:慢性應(yīng)激與孤養(yǎng)結(jié)合,電針治療21天,并于每天電針1h后進(jìn)行應(yīng)激造模。4.檢測(cè)指標(biāo)及方法:采用曠場(chǎng)實(shí)驗(yàn)(Open—field Test)、體質(zhì)量(Body Weight)和糖水偏好實(shí)驗(yàn)(Sucrose Preference Test)評(píng)價(jià)模型大鼠行為學(xué)改變情況,運(yùn)用Real-Time PCR技術(shù)檢測(cè)大鼠海馬組織PDE4A、PDE4DmRNA的含量,使用蛋白質(zhì)印跡法(Western Blot)檢測(cè)海馬組織PDE4A、PDE4D的蛋白表達(dá)水平。結(jié)果1.行為學(xué)變化實(shí)驗(yàn)前各組大鼠行為學(xué)表現(xiàn)均無統(tǒng)計(jì)學(xué)差異(p0.05)。實(shí)驗(yàn)結(jié)束后,體重、糖水消耗量及糖水偏好百分率、曠場(chǎng)實(shí)驗(yàn)水平穿越格數(shù)、垂直豎立次數(shù)空白組均高于模型組,有顯著性差異(P0.01);藥物組和電針治療組大鼠在以上方面,均高于與模型組,具有顯著性差異(P0.01);糖水消耗量方面,與藥物組相比,電針組大鼠的糖水消耗量沒有顯著性差異(p0.05);與糖水偏好百分率上,與藥物組相比,電針組大鼠的糖水偏好百分率高于藥物組,有統(tǒng)計(jì)學(xué)差異(p0.05)。2.海馬組織中PDE4A、PDE4D mmRNA表達(dá)PDE4A、PDE4DmRNA的含量,與空白組比較,模型組大鼠海馬表達(dá)的相對(duì)含量明顯增多(P0.01),而電針組大鼠海馬表達(dá)相對(duì)含量與模型組比較明顯減少(P0.01),且與空白組比較無統(tǒng)計(jì)學(xué)差異(P0.05)。與空白組比較,藥物組大鼠海馬表達(dá)相對(duì)含量無統(tǒng)計(jì)學(xué)差異(P0.05)。3.海馬組織中PDE4A、PDE4D蛋白相對(duì)表達(dá)含量PDE4A、PDE4D蛋白相對(duì)表達(dá)含量上,與空白組比較,模型組大鼠海馬蛋白表達(dá)相對(duì)含量明顯增多(P0.01),藥物組的表達(dá)也增多,有統(tǒng)計(jì)學(xué)差異(P0.05);電針組與藥物組在表達(dá)上有統(tǒng)計(jì)學(xué)差異,P0.01。結(jié)論1、氟西汀與電針的干預(yù)可改善抑郁癥狀,電針在改善快感缺失行為上有更明顯的優(yōu)勢(shì),可以提高對(duì)于獎(jiǎng)勵(lì)機(jī)制的反應(yīng)敏感性。2、PDE4A和PDE4D與抑郁癥存在著很大程度的關(guān)聯(lián)。3、電針可以通過抑制PDE4亞型中的PDE4A、PDE4DmRNA的表達(dá)來發(fā)揮其抗抑郁作用�？僧a(chǎn)生類似PDE4抑制劑對(duì)于抑郁癥的改善效果,而不涉及PDE4抑制劑的副作用。4、電針可能是通過抑制PDE4的與抑郁相關(guān)的幾個(gè)單一亞型,更專一地調(diào)控與抑郁相關(guān)的靶點(diǎn),進(jìn)而更好地發(fā)揮治療抑郁效果,這是其改善抑郁狀態(tài)的可能作用機(jī)制之一。
[Abstract]:Depression is a psychiatric disorder characterized by a combination of emotional symptoms characterized by long-term emotional depression. It has a high incidence of morbidity, disability and suicide, and has the characteristics of depression, anxiety, impaired mental activity, loss of appetite and insomnia. It has become a disease that greatly damages human health, according to the World Health Organization WH. Depression is ranked the fourth highest disease in the world, according to O. The global average incidence of depression is conservatively estimated to be about 11%. It is expected to be the second largest disease risk after heart disease in 2020, i.e. within five years. In China, the incidence of depression is about 3%-5%. More than 26 million people are suffering from depression. Recent epidemiological studies have shown that the lifetime prevalence of depression can reach 16%, ranking second highest in China's disease burden. Currently, there is no specific method to provide a perfect diagnostic solution for depression. Compared with Western antidepressants, acupuncture has a series of advantages, such as rapid onset, relatively minimal toxic and side effects, and relatively low cost. There have been a lot of research results on the mechanism of acupuncture in treating depression, but the target of its effect has not been fully clarified. Objective To study the effect of Electroacupuncture on behavioral observation of chronic stress depression model rats, and to explore the mechanism of electroacupuncture in treating depression by using molecular biology methods, so as to clarify the effect of Electroacupuncture on the expression of PDE4A and PDE4D. Methods 1. Animals were randomly divided into four groups: blank group, model control group, drug control group and electroacupuncture treatment group. Rats in each group were fed for one week before the experiment to adapt to the environment. Rats in blank group and other groups were fed in separate feeding rooms. Stimulation, including cold water swimming, water prohibition, day and night inversion, fasting, tail clipping, restraint, wet environment, a daily randomized stimulus, each stimulus averaged 3.3. Processing methods: blank group: 21 days under normal feeding conditions, using non-solitary mode, during which no stress stimulation; model control group.. Chronic stress model 21 days, and 21 days a day within 21 days a day. Drug control group: chronic stress plus orphanage, daily prescription, according to the proportion of 1 mg / 1 ml Prozac with distilled water, according to 2 mg / kg body weight, gastric administration, 1 hour after the administration of stress modeling, once a day for 21 days; Electroacupuncture treatment group: chronic stress and orphanage All rats were treated with electroacupuncture for 21 days, and the stress model was made after electroacupuncture for 1 hour every day. 4. Detection indexes and methods: The behavior changes of model rats were evaluated by open-field test, body weight and sucrose preference test, and the expression of PDE4A and PDE4D mRNA in hippocampus was detected by Real-Time PCR. Western Blot was used to detect the expression of PDE4A and PDE4D in the hippocampus. Results 1. There was no significant difference in the behavior of the rats before and after the experiment (p0.05). After the experiment, body weight, sugar consumption and sugar preference percentage, horizontal crossing lattice number, vertical erection times in open field experiment were observed. Compared with the model group, there was no significant difference in sugar consumption between the electroacupuncture group and the drug group (p0.05); and there was no significant difference in sugar consumption between the electroacupuncture group and the drug group (p0.05). Compared with the blank group, the relative content of PDE4A and PDE4D mRNA in the hippocampus of the model group increased significantly (P 0.01), while the relative content of PDE4A and PDE4D mRNA in the hippocampus of the electroacupuncture group was higher than that of the model group (P 0.05). Compared with the blank group, the relative expression of PDE4A and PDE4D protein in the hippocampus of the drug group was not significantly different (P 0.05). 3. The relative expression of PDE4A and PDE4D protein in the hippocampus of the model group was relative to that of the blank group. The content of fluoxetine was significantly increased (P 0.01), and the expression of drug group was also increased (P 0.05); the expression of fluoxetine was significantly different from that of drug group (P 0.01). Sex. 2, PDE4A and PDE4D are significantly associated with depression. 3. Electroacupuncture can exert its antidepressant effect by inhibiting the expression of PDE4A and PDE4D mRNA in PDE4 subtypes. It can produce an improvement effect similar to PDE4 inhibitors on depression, but does not involve the side effects of PDE4 inhibitors. 4. Electroacupuncture may inhibit PDE4 and depression. One of the possible mechanisms by which depression can be improved is that the related single subtypes more specifically regulate the targets associated with depression and thus play a better role in the treatment of depression.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R245
本文編號(hào)：2178097
[Abstract]:Depression is a psychiatric disorder characterized by a combination of emotional symptoms characterized by long-term emotional depression. It has a high incidence of morbidity, disability and suicide, and has the characteristics of depression, anxiety, impaired mental activity, loss of appetite and insomnia. It has become a disease that greatly damages human health, according to the World Health Organization WH. Depression is ranked the fourth highest disease in the world, according to O. The global average incidence of depression is conservatively estimated to be about 11%. It is expected to be the second largest disease risk after heart disease in 2020, i.e. within five years. In China, the incidence of depression is about 3%-5%. More than 26 million people are suffering from depression. Recent epidemiological studies have shown that the lifetime prevalence of depression can reach 16%, ranking second highest in China's disease burden. Currently, there is no specific method to provide a perfect diagnostic solution for depression. Compared with Western antidepressants, acupuncture has a series of advantages, such as rapid onset, relatively minimal toxic and side effects, and relatively low cost. There have been a lot of research results on the mechanism of acupuncture in treating depression, but the target of its effect has not been fully clarified. Objective To study the effect of Electroacupuncture on behavioral observation of chronic stress depression model rats, and to explore the mechanism of electroacupuncture in treating depression by using molecular biology methods, so as to clarify the effect of Electroacupuncture on the expression of PDE4A and PDE4D. Methods 1. Animals were randomly divided into four groups: blank group, model control group, drug control group and electroacupuncture treatment group. Rats in each group were fed for one week before the experiment to adapt to the environment. Rats in blank group and other groups were fed in separate feeding rooms. Stimulation, including cold water swimming, water prohibition, day and night inversion, fasting, tail clipping, restraint, wet environment, a daily randomized stimulus, each stimulus averaged 3.3. Processing methods: blank group: 21 days under normal feeding conditions, using non-solitary mode, during which no stress stimulation; model control group.. Chronic stress model 21 days, and 21 days a day within 21 days a day. Drug control group: chronic stress plus orphanage, daily prescription, according to the proportion of 1 mg / 1 ml Prozac with distilled water, according to 2 mg / kg body weight, gastric administration, 1 hour after the administration of stress modeling, once a day for 21 days; Electroacupuncture treatment group: chronic stress and orphanage All rats were treated with electroacupuncture for 21 days, and the stress model was made after electroacupuncture for 1 hour every day. 4. Detection indexes and methods: The behavior changes of model rats were evaluated by open-field test, body weight and sucrose preference test, and the expression of PDE4A and PDE4D mRNA in hippocampus was detected by Real-Time PCR. Western Blot was used to detect the expression of PDE4A and PDE4D in the hippocampus. Results 1. There was no significant difference in the behavior of the rats before and after the experiment (p0.05). After the experiment, body weight, sugar consumption and sugar preference percentage, horizontal crossing lattice number, vertical erection times in open field experiment were observed. Compared with the model group, there was no significant difference in sugar consumption between the electroacupuncture group and the drug group (p0.05); and there was no significant difference in sugar consumption between the electroacupuncture group and the drug group (p0.05). Compared with the blank group, the relative content of PDE4A and PDE4D mRNA in the hippocampus of the model group increased significantly (P 0.01), while the relative content of PDE4A and PDE4D mRNA in the hippocampus of the electroacupuncture group was higher than that of the model group (P 0.05). Compared with the blank group, the relative expression of PDE4A and PDE4D protein in the hippocampus of the drug group was not significantly different (P 0.05). 3. The relative expression of PDE4A and PDE4D protein in the hippocampus of the model group was relative to that of the blank group. The content of fluoxetine was significantly increased (P 0.01), and the expression of drug group was also increased (P 0.05); the expression of fluoxetine was significantly different from that of drug group (P 0.01). Sex. 2, PDE4A and PDE4D are significantly associated with depression. 3. Electroacupuncture can exert its antidepressant effect by inhibiting the expression of PDE4A and PDE4D mRNA in PDE4 subtypes. It can produce an improvement effect similar to PDE4 inhibitors on depression, but does not involve the side effects of PDE4 inhibitors. 4. Electroacupuncture may inhibit PDE4 and depression. One of the possible mechanisms by which depression can be improved is that the related single subtypes more specifically regulate the targets associated with depression and thus play a better role in the treatment of depression.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R245
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 景泉?jiǎng)P;楊利娟;劉俊彤;呂威;王鑫;盧夢(mèng)晗;邵千楓;李志剛;賽音朝克圖;;針刺治療抑郁癥的機(jī)制研究概況[J];中華中醫(yī)藥學(xué)刊;2017年01期
2 彭勁;彭文達(dá);朱茂;陳玲;顧星;;針灸預(yù)防腦卒中后抑郁癥的療效觀察[J];中醫(yī)藥導(dǎo)報(bào);2016年24期
3 徐英妹;黃文華;陳煒;;柴胡疏肝散聯(lián)合針灸治療原發(fā)性抑郁癥療效觀察[J];遼寧中醫(yī)雜志;2016年12期
4 Dong-mei Duan;Ya Tu;Ping Liu;Shuang Jiao;;Antidepressant effect of electroacupuncture regulates signal targeting in the brain and increases brainderived neurotrophic factor levels[J];Neural Regeneration Research;2016年10期
5 余旭奔;杜貫濤;劉廣軍;洪浩;;新型抗抑郁藥物分子靶標(biāo)研究進(jìn)展[J];藥學(xué)進(jìn)展;2016年08期
6 田紹俠;田賽;;中醫(yī)三聯(lián)療法治療抑郁癥36例臨床觀察[J];世界中醫(yī)藥;2016年06期
7 叢秀玲;高峰;;針灸解郁方治療抑郁癥的療效研究[J];新中醫(yī);2016年08期
8 任慧聰;谷世娜;趙琳;李文強(qiáng);張朝輝;;重復(fù)經(jīng)顱磁刺激對(duì)抑郁模型大鼠行為學(xué)及海馬區(qū)糖皮質(zhì)激素受體表達(dá)的影響[J];中國(guó)神經(jīng)精神疾病雜志;2016年07期
9 樊凌;趙劏琦;呂愛平;許能貴;劉建華;李滋平;吳泰相;歐愛華;符文彬;;針刺對(duì)抑郁癥大鼠海馬SNARE蛋白介導(dǎo)突觸前谷氨酸釋放的影響[J];中國(guó)老年學(xué)雜志;2016年13期
10 罕園園;代解杰;;抑郁癥動(dòng)物模型與其發(fā)病機(jī)制研究的進(jìn)展[J];中國(guó)實(shí)驗(yàn)動(dòng)物學(xué)報(bào);2016年03期
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