MC4R在颞叶癫痫患者及匹罗卡品大鼠模型脑组织中的表达及临床意义

发布时间：2018-02-27 04:10

本文关键词： MC4R 颞叶癫痫氯化锂-匹罗卡品模型　出处：《重庆医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：MC4R（Melanocortin Receptor-4）是一种广泛表达于中枢神经系统中的G蛋白偶联受体，介导了一系列重要的分子级联反应[1],研究表明，激活的MC4R可以上调AMPA受体(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor;α一氨基一3一羟基一5一甲基一4一异恶唑丙酸受体)的GluA1亚基在突触后膜的表达，增加其兴奋性传递，影响神经兴奋性及树突棘形态[2]。目前国内外尚无关于MC4R在癫痫中机制的研究。本研究旨在探究MC4R（Melanocortin Receptor-4）在癫痫患者及点燃的氯化锂-匹罗卡品大鼠模型脑组织中的表达及可能参与癫痫形成的机制。方法：从癫痫患者脑库中随机抽取20例癫痫患者脑组织，另取8例外伤病人减压手术切除脑组织作为对照。52只雄性SD大鼠经腹腔注射氯化锂-匹罗卡品造模，随机分为对照组、6h、24h、72h、7d (急性期)；14d、30d（潜伏期）；60d（慢性期）8个组，按不同时间点分别取模型鼠颞叶皮质及海马组织，用Western blot、免疫组织化学、免疫组织荧光等方法检测MC4R在癫痫患者及模型大鼠脑组织中的表达情况。结果：MC4R在模型大鼠的颞叶皮质及海马区均有表达，主要表达在神经元细胞膜及胞浆中。MC4R在癫痫患者脑组织中表达高于正常对照(P0.01)，在模型大鼠脑组织中，MC4R的表达在不同时间点均有升高（P0.05）,并于14d达到顶峰（P0.01）,慢性期开始略有下降，但仍高于对照组(p0.05)。结论：与对照组相比，MC4R在癫痫患者及匹罗卡品大鼠模型脑组织中均有显著升高。MC4R激发了多种信号通路，参与了多种病理生理过程，，本研究结果为癫痫的特异性诊断及靶向治疗提供了全新的作用靶点，有很高的临床及研究意义。
[Abstract]:Objective: MC4R (Melanocortin Receptor-4) is a widely expressed in the central nervous system of G protein coupled receptor is mediated by a series of important molecular cascade [1] study showed that the activation of MC4R can upregulate AMPA receptor alpha (-amino-3-hydroxy-5-methyl-4-isoxazole-propionic alpha acid receptor; a 3 amino hydroxy - methyl - 5 - 4 a isoxazole propionate receptor) expression of GluA1 subunits in the postsynaptic membrane, increase the excitatory transmission effect of nerve excitability and dendritic spine morphology of [2]. at home and abroad is about MC4R in epilepsy mechanism research. This study aimed to explore the expression of MC4R (Melanocortin Receptor-4) in the model of brain tissue in patients with epilepsy and lit lithium pilocarpine in rats and its possible mechanism involved in the formation of epilepsy.
Methods: randomly selected from the brain in epileptic patients in 20 patients with epilepsy in brain tissue, another 8 cases of trauma Decompression surgical resection of brain tissue as control.52 male SD rats by intraperitoneal injection of lithium pilocarpine model, were randomly divided into control group, 6h, 24h, 72h, 7d (acute period); 14d, 30d (latency); 60d (chronic) 8 groups at different time points were taken in a rat model of temporal lobe cortex and hippocampus of Western, blot, immunohistochemistry, immunofluorescence assay of MC4R in patients with epilepsy and brain tissues of rats in the expression.
Results: the expression of MC4R in rat model of temporal lobe cortex and hippocampus were mainly expressed in the neuronal cell membrane and cytoplasm in.MC4R is higher than the normal control expression in brain tissue of patients with epilepsy (P0.01), in the brain tissue of model rats, the expression of MC4R in different time points of high rise (P0.05). Peak in 14d (P0.01), and chronic period began to decline slightly, but still higher than the control group (P0.05).
Conclusion: compared with the control group, MC4R in patients with epilepsy and pilocarpine rat model of brain tissue were significantly increased in.MC4R stimulated several signaling pathways involved in many pathophysiological processes, the results of this study for the specific diagnosis and treatment of epilepsy target to provide a new target for clinical significance and research. Very high.

【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.1

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