难治性眩晕与焦虑障碍作用机制的初步探讨

发布时间：2018-04-23 05:33

本文选题：庆大霉素 + 周围性眩晕　；参考：《复旦大学》2012年博士论文

【摘要】：目的1)探索大鼠前庭功能损伤后其焦虑水平变化；2)探索前庭功能下降后前庭神经内侧核(MVN)与情绪相关的蓝斑核(LC)和中缝背核(DRN)中单胺类神经递质含量的变化；3)量化了解难治性周围性眩晕患者眩晕改善前后其焦虑及抑郁等情绪状态改变状况。方法1)本实验选用正常成年雄性SD大鼠作为研究对象,经鼓室注射30mg/ml庆大霉素(GT)作为前庭功能损伤动物模型,分别于不同时间点行转棒实验测定其下落潜伏期以评估前庭功能,还采用焦虑行为学平台高架十字迷宫和旷场实验评估焦虑水平变化；2)选用正常成年雄性SD大鼠作为研究对象,经鼓室注射30mg/mlGT作为前庭功能损伤动物模型,造模成功后,在不同时间点快速处死；取出新鲜脑组织,通过冰冻连续切片结合脑立体定位图谱用micropunch取出MVN,LC和DRN；随即采用高效液相色谱法检测去甲肾上腺素(NE),5羟色胺(5-HT)及其代谢物5羟吲哚乙酸(5-HIAA)和多巴胺(DA)及其代谢物二羟苯乙酸(DOPAC)等单胺类神经递质含量；3)入组单侧难治性周围性眩晕患者26例以及年龄与性别比例相似的正常对照组20例,所有受试者均知情同意并于眩晕干预治疗术前和术后3周分别完成4份情绪评估量表(HADS、SAS、SAS、SCL-90)。每一位对照组成员则完成相同的4份量表,分别统计分析术前组与对照组和术后组评分结果差异。结果1)转棒实验发现鼓室内GT注射6天组(GT-6d)大鼠降落平均潜伏期较对照组显著降低(P=0.009)；鼓室内GT注射2周组(GT-2w)同GT-6d组相比,平均潜伏期亦有所延长,但无明显统计学差异。旷场实验(OF)证实GT-3d组大鼠在旷场中探索距离显著减少(P0.05),而GT-2w组同对照组相比却无显著差异(P=1.000)。最后高架十字迷宫实验(EPM)也发现GT-3d组大鼠的开放臂进入次数较对照组进入开放臂次数显著减少(P=0.02),GT-2w组同对照组相比亦无显著差异(P=0.181),上述结果反映出鼓室内GT注射会导致大鼠前庭功能受损,而随着时间推移,会得到部分代偿。与之相应,EPM实验发现GT-3d组大鼠开放臂时间和开放臂进入次数较对照组显著减少,OF实验也发现GT-3d大鼠与GT-2w组的中央区域活动时间同对照组对比有显著下降,提示鼓室内GT注射3天时大鼠的焦虑水平显著升高,2周后随着前庭功能的代偿,水平有所降低,但未到正常水平；2)鼓室内GT-3d后大鼠MVN中NE和5-HIAA含量均较对照组有显著的增加,而DA和其代谢物DOPAC含量较假手术后3天组含量也有显著增加；GT-3d组LC中NE、5-HT和5-HIAA含量均较对照组有显著的增加,而DOPAC含量较S-3d组含量也有显著增加；GT-3d组在DRN中NE、5-HT、5-HIAA和DOPAC较对照组有显著增加,从而提示MVN-LC和MVN-DRN通路的激活。3)眩晕术前组与正常对照组在HAD, SAS, SDS及SCL-90四个量表的评分均可见显著差异,提示顽固性周围性眩晕患者的焦虑及抑郁水平较正常人为高,部分患者已达到抑郁症诊断标准。眩晕术前组与术后组在HAD, SAS, SDS及SCL-90四个量表的评分均可见差异(HAD,p0.05)或显著差异(SAS, SDS, SCL-90;p0.01),提示眩晕干预治疗后患者的焦虑及抑郁水平随着眩晕的控制而降低。结论1)通过行为学实验发现前庭功能部分损伤的动物模型焦虑水平明显升高,而随着时间推移,其焦虑水平随着前庭功能的代偿而有所下降,证实前庭功能受损会导致焦虑等情绪水平改变。2)通过高效液相色谱法发现前庭功能损伤3天后这些核团中均出现了部分或全部单胺类递质含量的增加,2周后部分递质含量出现降低。从神经生物学角度证实前庭功能受损会导致焦虑等情绪水平升高,而随着前庭代偿,焦虑水平也会有望随之缓解。3)顽固性周围性眩晕患者较正常前庭功能者焦虑与抑郁水平明显升高,而接受眩晕干预治疗后,其焦虑及抑郁情绪障碍得到改善,从临床上证实周围性眩晕与焦虑等情绪障碍间具有相互作用。4)提示我们在临床工作中对于合并焦虑、抑郁等情绪障碍的周围性眩晕患者,应在治疗眩晕症状的同时,辅以行为认知治疗甚至精神药物治疗等综合治疗改善焦虑等情绪障碍,以求最大程度改善这类患者的预后。
[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.

【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R764

【参考文献】