前庭损伤急性期低血压兴奋MVN的NMDA受体机制

发布时间：2018-05-24 12:23

本文选题：急性低血压 + 前庭神经内侧核　；参考：《延边大学》2011年硕士论文

【摘要】：有研究报道,在麻醉动物静脉注射硝普钠(Sodium nitroprusside, SNP)诱发急性低血压时,流经末梢前庭器官的血流量与血压的降低呈正相关,使前庭神经传入冲动增加,释放兴奋性神经递质—谷氨酸(Glutamate, Glu),来兴奋前庭神经内侧核(medial vestibular nucleus, MVN),并可使MVN区c-Fos蛋白表达增加。本研究利用免疫组织化学方法和药理学方法,在一侧外周前庭器官损伤急性期清醒大鼠,观察了急性低血压时前庭神经内侧核区c-Fos蛋白的表达情况,并探讨了其可能的Glu-NMDA受体机制。选择雄性Wistar系清洁级大鼠96只,体重在250±30g,随机分为三个大组,即前庭器官正常组、单侧前庭器官破坏组、NMDA受体组。前庭器官正常组又分对照组(n=6)和实验组(n=6),分别静脉注射生理盐水和硝普钠诱发急性低血压；前庭器官破坏组首先用对氨基苯砷酸盐单纯破坏外周前庭器官6、12、24、48、72h后观察MVN区c-Fos蛋白表达的情况,进而再分为对照组和实验组,观察外周前庭器官假破坏与真破坏后急性低血压对MVN区c-Fos蛋白表达的影响；NMDA受体组分为NMDA受体激动剂组和阻断剂组,分别向侧脑室注射NMDA和MK-80110min后,观察了急性低血压的效应,对照组为人工脑脊液代替激动激或阻断剂、生理盐水代替硝普钠。各组实验均在动物清醒状态下进行。结果如下： 1.在正常动物诱发急性低血压后MVN区c-Fos蛋白有明显表达,但在对照组则无明显表达。 2.单纯破坏一侧外周前庭器官6、24、48、72h时,破坏同侧MVN区c-Fos蛋白无明显表达,但在其对侧则有明显的表达,尤其是48h最为显著。而在破坏12h时呈现为反向表达,即损伤同侧表达增多,而损伤对侧仅低水平表达。 3.破坏单侧前庭器官48h后诱发急性低血压时,破坏同侧MVN区c-Fos蛋白无明显表达,但对侧有明显表达。破坏单侧前庭器官后静脉注射生理盐水的对照组则较实验组相比表达不甚明显,两者之间有显著性差异。在其对照组,即进行假前庭破坏后诱发急性低血压后,则表现为两侧MVN区c-Fos蛋白对称性分布,与实验组相比有显著性差异。 4.正常动物侧脑室注射Glu受体兴奋剂(NMDA),双侧MVN区均有明显的c-Fos蛋白表达,与侧脑室注射人工脑脊液的对照组相比有显著性差异。 5.侧脑室注射阻断剂(MK-801)后注射SNP诱发急性低血压,双侧MVN区只见少量的c-Fos表达,而在侧脑室注射人工脑脊液后诱发急性低血压,双侧MVN区则可见对称性的c-Fos蛋白表达增加,与生理盐水对照组相比未见明显差异。结论： 1.清醒动物破坏一侧前庭器官早期,除12h时损伤侧MVN区c-Fos蛋白表达多于对侧以外,6、24、48、72h损伤对侧多于损伤侧,而且48h表达最明显； 2.清醒动物急性低血压诱发的MVN兴奋可能有Glu的NMDA受体参与。
[Abstract]:It has been reported that when sodium nitroprusside (SNPs) is injected intravenously into anesthetized animals to induce acute hypotension, the blood flow through vestibular organs is positively correlated with the decrease of blood pressure, which increases the afferent impulse of vestibular nerve. The release of excitatory neurotransmitter glutamate Glutamate (Glutamate) was used to excite medial vestibular nucleus, MVNs in medial vestibular nucleus, and to increase the expression of c-Fos protein in MVN region. In this study, immunohistochemical and pharmacological methods were used to observe the expression of c-Fos protein in medial vestibular nucleus during acute stage of peripheral vestibular organ injury in rats with acute hypotension. The possible mechanism of Glu-NMDA receptor was discussed. 96 male Wistar clean grade rats, weighing 250 卤30 g, were randomly divided into three groups: normal vestibular organ group and unilateral vestibular organ destruction group. The normal vestibular organ group was divided into control group (n = 6) and experimental group (n = 6). The acute hypotension was induced by intravenous injection of normal saline and sodium nitroprusside respectively. In the vestibular organ destruction group, the expression of c-Fos protein in the MVN region was observed 72 hours after the destruction of the peripheral vestibular organ with p-aminobenzene arsenate alone, and was further divided into two groups: control group and experimental group. To observe the effect of acute hypotension on the expression of c-Fos protein in MVN region after peripheral vestibular organ pseudodestruction and true destruction, NMDA receptor groups were divided into NMDA receptor agonist group and blocker group. The effect of acute hypotension was observed after injecting NMDA and MK-80110min into lateral ventricle, respectively. The control group was treated with artificial cerebrospinal fluid (CSF) instead of stimulation or blocking agent and saline as sodium nitroprusside. All the experiments were carried out in the conscious state of the animals. The results are as follows: 1. The expression of c-Fos protein in the MVN region was significant after acute hypotension induced by normal animals, but not in the control group. 2. No significant expression of c-Fos protein was found in ipsilateral MVN region after the destruction of the unilateral vestibular organ 62448h for 72 h, but there was obvious expression in the contralateral side, especially at 48h. The reverse expression was found at 12 h after injury, that is, the ipsilateral expression was increased, but the contralateral expression was only low. 3. When acute hypotension was induced 48 hours after unilateral vestibular organ destruction, there was no obvious expression of c-Fos protein in ipsilateral MVN region, but obvious expression in contralateral side. The expression of normal saline after destroying unilateral vestibular organs in the control group was not obvious compared with the experimental group, and there was a significant difference between the two groups. After acute hypotension was induced by pseudovestibular destruction in the control group, the distribution of c-Fos protein in the bilateral MVN region was symmetrically distributed, which was significantly different from that in the experimental group. 4. In normal animals, the expression of c-Fos protein in the bilateral MVN region was significantly higher than that in the control group injected with artificial cerebrospinal fluid (ACSF) by intraventricular injection of Glu receptor stimulant (NMDAA). 5. Acute hypotension induced by SNP was induced by intraventricular injection of blocker MK-801. Only a small amount of c-Fos was expressed in bilateral MVN region, while acute hypotension was induced by intracerebroventricular injection of artificial cerebrospinal fluid (ACSF). Symmetrical expression of c-Fos protein was observed in bilateral MVN region. There was no significant difference compared with normal saline control group. Conclusion: 1. At the early stage of destroying one vestibular organ, the expression of c-Fos protein in the MVN region of the injured side was higher than that in the contralateral side at 72 h after injury, and the expression was the most obvious at 48 h. 2. MVN stimulation induced by acute hypotension in conscious animals may involve Glu NMDA receptor.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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