難治性眩暈與焦慮障礙作用機(jī)制的初步探討
發(fā)布時(shí)間：2018-04-23 05:33
本文選題：慶大霉素 + 周?chē)匝?/strong> ； 參考：《復(fù)旦大學(xué)》2012年博士論文
【摘要】：目的1)探索大鼠前庭功能損傷后其焦慮水平變化；2)探索前庭功能下降后前庭神經(jīng)內(nèi)側(cè)核(MVN)與情緒相關(guān)的藍(lán)斑核(LC)和中縫背核(DRN)中單胺類(lèi)神經(jīng)遞質(zhì)含量的變化；3)量化了解難治性周?chē)匝灮颊哐灨纳魄昂笃浣箲]及抑郁等情緒狀態(tài)改變狀況。 方法1)本實(shí)驗(yàn)選用正常成年雄性SD大鼠作為研究對(duì)象,經(jīng)鼓室注射30mg/ml慶大霉素(GT)作為前庭功能損傷動(dòng)物模型,分別于不同時(shí)間點(diǎn)行轉(zhuǎn)棒實(shí)驗(yàn)測(cè)定其下落潛伏期以評(píng)估前庭功能,還采用焦慮行為學(xué)平臺(tái)高架十字迷宮和曠場(chǎng)實(shí)驗(yàn)評(píng)估焦慮水平變化；2)選用正常成年雄性SD大鼠作為研究對(duì)象,經(jīng)鼓室注射30mg/mlGT作為前庭功能損傷動(dòng)物模型,造模成功后,在不同時(shí)間點(diǎn)快速處死；取出新鮮腦組織,通過(guò)冰凍連續(xù)切片結(jié)合腦立體定位圖譜用micropunch取出MVN,LC和DRN；隨即采用高效液相色譜法檢測(cè)去甲腎上腺素(NE),5羥色胺(5-HT)及其代謝物5羥吲哚乙酸(5-HIAA)和多巴胺(DA)及其代謝物二羥苯乙酸(DOPAC)等單胺類(lèi)神經(jīng)遞質(zhì)含量；3)入組單側(cè)難治性周?chē)匝灮颊?6例以及年齡與性別比例相似的正常對(duì)照組20例,所有受試者均知情同意并于眩暈干預(yù)治療術(shù)前和術(shù)后3周分別完成4份情緒評(píng)估量表(HADS、SAS、SAS、SCL-90)。每一位對(duì)照組成員則完成相同的4份量表,分別統(tǒng)計(jì)分析術(shù)前組與對(duì)照組和術(shù)后組評(píng)分結(jié)果差異。 結(jié)果1)轉(zhuǎn)棒實(shí)驗(yàn)發(fā)現(xiàn)鼓室內(nèi)GT注射6天組(GT-6d)大鼠降落平均潛伏期較對(duì)照組顯著降低(P=0.009)；鼓室內(nèi)GT注射2周組(GT-2w)同GT-6d組相比,平均潛伏期亦有所延長(zhǎng),但無(wú)明顯統(tǒng)計(jì)學(xué)差異。曠場(chǎng)實(shí)驗(yàn)(OF)證實(shí)GT-3d組大鼠在曠場(chǎng)中探索距離顯著減少(P0.05),而GT-2w組同對(duì)照組相比卻無(wú)顯著差異(P=1.000)。最后高架十字迷宮實(shí)驗(yàn)(EPM)也發(fā)現(xiàn)GT-3d組大鼠的開(kāi)放臂進(jìn)入次數(shù)較對(duì)照組進(jìn)入開(kāi)放臂次數(shù)顯著減少(P=0.02),GT-2w組同對(duì)照組相比亦無(wú)顯著差異(P=0.181),上述結(jié)果反映出鼓室內(nèi)GT注射會(huì)導(dǎo)致大鼠前庭功能受損,而隨著時(shí)間推移,會(huì)得到部分代償。與之相應(yīng),EPM實(shí)驗(yàn)發(fā)現(xiàn)GT-3d組大鼠開(kāi)放臂時(shí)間和開(kāi)放臂進(jìn)入次數(shù)較對(duì)照組顯著減少,OF實(shí)驗(yàn)也發(fā)現(xiàn)GT-3d大鼠與GT-2w組的中央?yún)^(qū)域活動(dòng)時(shí)間同對(duì)照組對(duì)比有顯著下降,提示鼓室內(nèi)GT注射3天時(shí)大鼠的焦慮水平顯著升高,2周后隨著前庭功能的代償,水平有所降低,但未到正常水平；2)鼓室內(nèi)GT-3d后大鼠MVN中NE和5-HIAA含量均較對(duì)照組有顯著的增加,而DA和其代謝物DOPAC含量較假手術(shù)后3天組含量也有顯著增加；GT-3d組LC中NE、5-HT和5-HIAA含量均較對(duì)照組有顯著的增加,而DOPAC含量較S-3d組含量也有顯著增加；GT-3d組在DRN中NE、5-HT、5-HIAA和DOPAC較對(duì)照組有顯著增加,從而提示MVN-LC和MVN-DRN通路的激活。3)眩暈術(shù)前組與正常對(duì)照組在HAD, SAS, SDS及SCL-90四個(gè)量表的評(píng)分均可見(jiàn)顯著差異,提示頑固性周?chē)匝灮颊叩慕箲]及抑郁水平較正常人為高,部分患者已達(dá)到抑郁癥診斷標(biāo)準(zhǔn)。眩暈術(shù)前組與術(shù)后組在HAD, SAS, SDS及SCL-90四個(gè)量表的評(píng)分均可見(jiàn)差異(HAD,p0.05)或顯著差異(SAS, SDS, SCL-90;p0.01),提示眩暈干預(yù)治療后患者的焦慮及抑郁水平隨著眩暈的控制而降低。 結(jié)論1)通過(guò)行為學(xué)實(shí)驗(yàn)發(fā)現(xiàn)前庭功能部分損傷的動(dòng)物模型焦慮水平明顯升高,而隨著時(shí)間推移,其焦慮水平隨著前庭功能的代償而有所下降,證實(shí)前庭功能受損會(huì)導(dǎo)致焦慮等情緒水平改變。2)通過(guò)高效液相色譜法發(fā)現(xiàn)前庭功能損傷3天后這些核團(tuán)中均出現(xiàn)了部分或全部單胺類(lèi)遞質(zhì)含量的增加,2周后部分遞質(zhì)含量出現(xiàn)降低。從神經(jīng)生物學(xué)角度證實(shí)前庭功能受損會(huì)導(dǎo)致焦慮等情緒水平升高,而隨著前庭代償,焦慮水平也會(huì)有望隨之緩解。3)頑固性周?chē)匝灮颊咻^正常前庭功能者焦慮與抑郁水平明顯升高,而接受眩暈干預(yù)治療后,其焦慮及抑郁情緒障礙得到改善,從臨床上證實(shí)周?chē)匝炁c焦慮等情緒障礙間具有相互作用。4)提示我們?cè)谂R床工作中對(duì)于合并焦慮、抑郁等情緒障礙的周?chē)匝灮颊?應(yīng)在治療眩暈癥狀的同時(shí),輔以行為認(rèn)知治療甚至精神藥物治療等綜合治療改善焦慮等情緒障礙,以求最大程度改善這類(lèi)患者的預(yù)后。
[Abstract]:Objective 1) to explore the changes in the level of anxiety after the vestibular function injury in rats; 2) to explore the changes in the content of monoamine neurotransmitters in the vestibular medial nucleus (MVN) and the mood related locus nucleus (LC) and the dorsal raphe nucleus (DRN) after the vestibular function decreased; 3) to quantify the anxiety and depression before and after the improvement of the vertigo in the patients with refractory peripheral vertigo. The state of the ready state changes.
Method 1) a normal adult male SD rat was selected as the research object. 30mg/ml gentamicin (GT) was injected into the tympanic cavity as an animal model of vestibular function injury. The incubation experiment was performed at different time points to evaluate the latent period of the fall to evaluate the vestibular function. The test of the elevated cross maze and the open field test on the platform of anxiety behavior was also used. The change of anxiety level; 2) the normal adult male SD rats were selected as the research object, 30mg/mlGT was injected through the tympanic cavity as the animal model of the vestibular function injury. After the model was successful, the rats were executed quickly at different time points. The fresh brain tissue was taken out and the MVN, LC and DRN were removed by the frozen continuous slice combined with the brain stereotactic map with micropunch, and then the LC and DRN were taken out. High performance liquid chromatography was used to detect the content of norepinephrine (NE), 5 hydroxytryptamine (5-HT) and its metabolite 5 hydroxyindoloacetic acid (5-HIAA) and dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC), and other monoamine neurotransmitters; 3) 26 cases of unilateral refractory peripheral vertigo patients and normal control group with similar age to sex ratio 20 For example, all subjects informed consent and completed 4 emotional assessment scales before and 3 weeks after vertigo intervention (HADS, SAS, SAS, SCL-90). Each control group completed the same 4 scales, and analyzed the difference between the pre operation group and the control group and the postoperative group.
Results 1) the rotation stick experiment found that the average latency period of the GT injection in the 6 day group (GT-6d) was significantly lower than that of the control group (P=0.009). The average latency period of the GT injection group (GT-2w) in the tympanum was also longer than that in the GT-6d group, but there was no significant difference. The open field test (OF) confirmed that the distance of the rats in the GT-3d group was significantly reduced in the open field. There was no significant difference (P0.05), but there was no significant difference between the GT-2w group and the control group (P=1.000). Finally, the elevated cross maze test (EPM) also found that the number of open arm entry times in the GT-3d group was significantly lower than that of the control group (P=0.02), and there was no significant difference in the GT-2w group from the control group (P=0.181). The results reflected the GT injection in the drum chamber. The vestibular function of the rats was damaged, and some compensation was obtained with time. Correspondingly, the EPM experiment found that the open arm time and the number of open arm entry times in group GT-3d rats were significantly lower than those of the control group. The OF experiment also found that the central regional activity time of the GT-3d rats and the GT-2w group was significantly lower than that of the control group, suggesting GT in the drum room. The level of anxiety in rats increased significantly at 3 days of injection. After 2 weeks, the level of the vestibular function was reduced, but the level of NE and 5-HIAA in MVN after GT-3d in the tympanic rats increased significantly, while the content of DA and its metabolite DOPAC content were also significantly increased in the 3 day group after the sham operation, and LC in GT-3d group LC. The content of NE, 5-HT and 5-HIAA increased significantly compared with that of the control group, while the content of DOPAC was significantly higher than that in the S-3d group, and the GT-3d group had a significant increase in NE, 5-HT, 5-HIAA and DOPAC compared with the control group in DRN. The scores were significantly different, suggesting that the anxiety and depression levels of the patients with intractable peripheral vertigo were higher than those of the normal ones. Some of the patients had reached the diagnostic criteria for depression. The scores of four scales of HAD, SAS, SDS and SCL-90 in the pre dizziness group and the postoperative group were all different (HAD, P0.05) or significant differences (SAS, SDS, SCL-90; P0.01), suggesting vertigo. The level of anxiety and depression after intervention treatment decreased with the control of vertigo.
Conclusion 1) the model anxiety level of the vestibular part of the animal model was significantly increased by the behavioral experiment, and the anxiety level decreased with the vestibular function over time. It proved that the impairment of vestibular function could lead to anxiety and other emotional level changes.2) through high performance liquid chromatography (HPLC) to find the vestibular function injury for 3 days. Some or all of the monoamine transmitters were increased in all of these nuclei, and the content of partial transmitters decreased after 2 weeks. From the neurobiological point of view, the impairment of vestibular function could lead to anxiety and other emotional levels, and with the vestibular compensation, the level of anxiety could also be expected to alleviate the.3) Jiao Zhengchang, the refractory peripheral vertigo. The level of anxiety and depression in the vestibule function increased significantly, and the anxiety and depression disorder was improved after the intervention of vertigo intervention. The interaction of peripheral vertigo with anxiety and other emotional disorders was confirmed clinically. It suggested that the patients with peripheral vertigo combined with anxiety and depression, such as anxiety and depression, were.4 in clinical work. In order to improve the prognosis of these patients, it is necessary to treat the symptoms of vertigo at the same time, supplemented by comprehensive treatment, such as behavioral cognitive therapy and even psychotherapy, to improve anxiety and other emotional disorders.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R764
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