难治性癫痫患者致痫灶中HCN1、GABA_A α 1、A2a的表达
发布时间：2018-05-30 03:19
本文选题：难治性癫痫 + 睡眠 ； 参考：《吉林大学》2014年硕士论文
【摘要】：目的： 离子通道变异、神经递质改变、睡眠因子改变以及神经网络重塑等均参与了癫痫的发生，但癫痫的发病机制错综复杂，仍不十分清楚。本研究探讨难治性癫痫患者致痫灶中HCN1、GABAA受体α1亚基以及腺苷A2a受体的表达。 方法： 24例难治性癫痫患者（实验组）行癫痫致痫灶切除术，6例行尸体解剖者（对照组）剖检，两组术后标本进行光镜、电镜及免疫组化检查，观察HCN1、GABAA受体α1亚基以及腺苷A2a受体三者的表达变化。 结果： 1.实验组脑组织光镜下可见神经元分布不均匀，神经元丢失、变性，胞核呈空泡状，胞质少，胶质细胞增生以及噬神经细胞现象、卫星现象等病理改变。电镜下可见细胞核异染色质凝集，呈块状，近核膜排列或散在分布；核基质略致密；胞质内粗面内质网扩张，部分线粒体嵴断裂，基质局部空化；可见多个空泡。 2.实验组和对照组均可见HCN1、GABAAα1、A2a蛋白表达的阳性细胞，三者在神经元细胞实验组阳性表达率分别为79.4%，95.0%，94.8；对照组阳性表达率分别为94.8%，76.7%，77.5%。三者在两组间差异具有统计学意义（P㩳0.01）。胶质细胞实验组中HCN1、GABAAα1阳性表达率与对照组之间无统计学差异（79.3%vs.81.8%,67.3%vs.64.7%；P0.05），A2a蛋白表达两组间具有显著统计学意义（89.1%vs.77.4%, P 0.01）。 3.将实验组难治性癫痫患者按照取材部位分为额叶、颞叶两组，统计两组中HCN1、GABAAα1、A2a的表达情况。额颞两组间HCN1阳性表达率有统计学差异(92.4%vs.82.9%,P 0.01)；而两组间GABAAα1、A2a阳性表达率无明显差异(93.3%vs.90.6%,94.4%vs.94.8%, P0.05)。根据发作频率将实验组患者分为每月发作＜10次、每月发作≥10次两组，统计两组中HCN1、GABAAα1、A2a的表达情况。HCN1, A2a的阳性表达率发作频率高组与发作频率低组之间有明显差异(91.7%vs.83.1%,89.2%vs.96.4%,P0.01)，但两组间GABAAα1表达无明显差异(90.9%vs.91.5%, P0.05)。 4.实验组患者术前行PSQI评分，分为PSQI㩳5、6-10、11-15、PSQI㧐16四组，，统计四组中睡眠相关因子HCN1、GABAAα1、A2a蛋白表达水平。PSQI㩳5与PSQI㧐16两组的HCN1、A2a阳性率之间无显著差异(95.6%vs.94.3%,81.0%vs.83.9%, P0.05),两组间GABAA受体α1亚单位表达率有统计学差异(97.4%vs.91.6%, P0.01)。 结论： 1.HCN1、GABAAα1、A2a在难治性癫痫患者致痫灶神经元及胶质细胞中广泛表达； 2.难治性癫痫患者HCN1通道表达降低，且HCN1表达情况与发病频率相关。难治性癫痫患者致痫灶内GABAA受体α1亚单位表达增加，与亚单位类型、受体表达的部位和癫痫状态有关。难治性癫痫患者致痫灶脑组织中A2a受体表达活跃，腺苷受体表达与癫痫病程具有时间相关性。 3. PSQI㧐16患者脑组织中GABAA受体α1亚单位表达降低。
[Abstract]:Objective: Ion channel variation, neurotransmitter changes, sleep factor changes and neural network remodeling are all involved in the occurrence of epilepsy. However, the pathogenesis of epilepsy is complex and unclear. This study was to investigate the expression of GABAA receptor 伪 1 subunit and adenosine A 2a receptor in epileptogenic foci of patients with intractable epilepsy. Methods: Twenty-four patients with intractable epilepsy (experimental group) underwent excision of epileptogenic foci and 6 cases of cadaveric dissection (control group). The specimens of both groups were examined by light microscope, electron microscope and immunohistochemistry. The expression of GABAA receptor 伪 1 subunit and adenosine A 2a receptor were observed. Results: 1. In the experimental group, the distribution of neurons was uneven, the neurons were lost, denatured, the nucleus was vacuolated, the cytoplasm was low, glial cell proliferation, neuronal phagocytosis, satellite phenomenon and other pathological changes were observed under the light microscope. Under electron microscope, nuclear heterochromatin agglutination was seen, which was massive, near nuclear membrane arrangement or scattered; nuclear matrix was slightly dense; cytoplasmic rough endoplasmic reticulum dilated; part of mitochondria crest was broken, matrix was local cavitation, and several vacuoles were observed. 2. The positive expression rates of GABAA 伪 1a 2a protein were found in the experimental group and the control group respectively. The positive expression rates of the three proteins in the neuron cell experimental group were 79.4% and 95.0% respectively, and the positive expression rates in the control group were 94.8% and 77.5%, respectively. The difference between the three groups was statistically significant (P < 0.01). There was no significant difference in the expression rate of GABAA 伪 1 between the glial cells experimental group and the control group. There was no significant difference between the two groups in the expression of HCN1- GABAA 伪 1 protein. There was a significant difference between the two groups in the expression of HCN1 + GABAA 伪 1 protein. 3. The patients with intractable epilepsy in the experimental group were divided into frontal lobe group and temporal lobe group according to the location of the material, and the expression of GABAA 伪 1a 2a in the two groups was counted. There was significant difference in the positive expression rate of HCN1 between the two groups (92.4vs.82.9) and between the two groups (P 0.01a), but there was no significant difference in the positive expression rate of GABAA 伪 1a A2a between the two groups. There was no significant difference between the two groups (93.3 vs.90.6) and 94.4vs.94.8. According to the frequency of attack, the patients in the experimental group were divided into two groups: the number of seizures < 10 times per month and the number of episodes 鈮
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