本文選題：雷帕霉素 + 大腦皮質(zhì)發(fā)育畸形　； 參考：《西南醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:觀察雷帕霉素對中年期MCD大鼠模型學(xué)習(xí)記憶能力及自發(fā)性癲癇的影響,探討雷帕霉素對MCD是否具有保護(hù)作用,從而對難治性癲癇的藥物治療提供新的依據(jù)。方法:將懷孕17天大鼠進(jìn)行X射線照射,所生子一代大鼠隨機(jī)選取為MCD大鼠模型組,將未照射懷孕大鼠所生子一代大鼠隨機(jī)選取設(shè)定為正常對照組,兩組大鼠分別培養(yǎng)至51周(中年期)。各組內(nèi)分為雷帕霉素組、溶劑組和生理鹽水組,分別予以腹腔注射上述藥物30天。每組大鼠藥物注射前后進(jìn)行Morris水迷宮檢測,測定逃生潛伏期、目標(biāo)象限路程比、穿越平臺次數(shù),判斷其學(xué)習(xí)記憶能力前后有無變化。后行腦電圖監(jiān)測,統(tǒng)計(jì)各組大鼠左右兩側(cè)大腦半球癇性波發(fā)放次數(shù)。最后灌注固定大鼠,取出腦組織,測定大鼠腦組織前后徑、左右徑、上下徑、體積、重量,行石蠟切片、HE染色。視頻監(jiān)控持續(xù)藥物注射前、中、后共三個(gè)月,各階段選取8天人工觀察自發(fā)性癲癇發(fā)作情況。結(jié)果:1、Morris水迷宮逃生潛伏期:注射藥物前比較,模型組和正常組顯示出明顯差異,模型組內(nèi)任意一組與正常組內(nèi)任意一組比較差異均有意義。模型組藥物注射前后比較,各組前后對應(yīng)天數(shù)逃生潛伏期差異無統(tǒng)計(jì)學(xué)意義。Morris水迷宮目標(biāo)象限路程比和穿越平臺次數(shù):注射藥物前比較,模型組內(nèi)雷帕霉素組與正常組內(nèi)雷帕霉素組比較,差異有意義。模型組藥物注射前后比較,各組注射前后對應(yīng)天數(shù)對比差異均無意義。2、腦電圖:雙側(cè)大腦半球?qū)?yīng)部位(額葉、頂葉、海馬)同時(shí)放電。正常組大鼠腦電圖仍顯示尖波、棘波、棘慢復(fù)合波,平均每分鐘發(fā)作次數(shù)明顯低于模型組,正常組內(nèi)各組差異無統(tǒng)計(jì)學(xué)意義。模型組內(nèi)癇性尖波發(fā)作次數(shù)雷帕霉素組溶劑組生理鹽水組;雷帕霉素組與后兩組分別比較差異均有統(tǒng)計(jì)學(xué)意義;溶劑組、生理鹽水組比較差異無統(tǒng)計(jì)學(xué)意義。模型組內(nèi)雷帕霉素組和正常組內(nèi)溶劑組、生理鹽水組比較差異無統(tǒng)計(jì)學(xué)意義。3、長程視頻監(jiān)控:正常組及模型組均未觀察到Racine分級達(dá)3級及其以上者。4、大體、病理結(jié)果:與正常組相比,模型組腦組織體積、重量、前后徑、左右徑、上下徑均減小,差異有統(tǒng)計(jì)學(xué)意義。正常組內(nèi)各組差異無統(tǒng)計(jì)學(xué)意義;模型組內(nèi)各組差異無統(tǒng)計(jì)學(xué)意義。HE染色結(jié)果顯示正常組皮層結(jié)構(gòu)清晰,分層明顯,細(xì)胞排列整齊,未見異常神經(jīng)元;模型組雷帕霉素組出現(xiàn)胼胝體缺失,腦室擴(kuò)大,皮層結(jié)構(gòu)紊亂,神經(jīng)元極性紊亂、疏密不均,可見異常神經(jīng)元,海馬CA1區(qū)可見結(jié)節(jié)。結(jié)論:本實(shí)驗(yàn)條件下:1、195cGyX射線照射母鼠所生子一代制備MCD大鼠模型成功,此方法簡單可靠。2、雷帕霉素可能降低中年期MCD大鼠模型癇性波的發(fā)生率。3、雷帕霉素對中年期MCD大鼠模型學(xué)習(xí)記憶能力無明顯改善作用,且對已形成的腦部病理損害無逆轉(zhuǎn)作用。
[Abstract]:Aim: to observe the effects of rapamycin on learning and memory ability and spontaneous epilepsy in middle-aged MCD rats, and to explore whether rapamycin has protective effect on MCD and provide a new basis for drug treatment of intractable epilepsy. Methods: after 17 days of pregnancy rats were exposed to X ray, the first generation of offspring was randomly selected as MCD rat model group, and the first generation of unirradiated pregnant rats was randomly selected as normal control group. The rats in the two groups were cultured to 51 weeks (middle age). Each group was divided into rapamycin group, solvent group and saline group. The Morris water labyrinth was detected before and after drug injection in each group. The latency of escape, the ratio of target quadrant distance to distance, the times of crossing the platform were determined to determine whether the ability of learning and memory changed before and after the drug injection. After EEG monitoring, the number of epileptic waves in the left and right cerebral hemispheres of the rats in each group was counted. At last, the rat brain tissue was fixed by perfusion, and the anteroposterior, left and right diameters, superior and inferior diameters, volume and weight of brain tissue were measured, and the paraffin sections were stained with HE. Before, during and after three months of continuous drug injection, 8 days were selected to observe the spontaneous seizures. Results the escape latency of the water maze was significantly different between the model group and the normal group before injection, and there was significant difference between any group in the model group and any group in the normal group. There was no significant difference in the escape latency of the corresponding days in the model group before and after injection. Morris water maze target quadrant distance ratio and the times of crossing the platform: comparison before injection; There was significant difference between the model group and the normal group. There was no significant difference in the corresponding days before and after injection in the model group. Electroencephalogram (EEG): the corresponding parts (frontal lobe, parietal lobe, hippocampus) of bilateral cerebral hemispheres were discharges at the same time. The EEG of normal group still showed sharp wave, spike wave, spine-slow complex wave, the average attack times per minute was significantly lower than that of model group, but there was no significant difference in each group in normal group. The number of epileptic spikes in the model group was significantly higher than that in the solvent group and the rapamycin group. There was no significant difference between the solvent group and the latter two groups. There was no significant difference between the solvent group and the saline group. There was no significant difference between the model group and the normal group. There was no significant difference between the normal saline group and the model group. The long-term video surveillance showed that no Racine grade of grade 3 or above was observed in the normal group and the model group. Pathological results: compared with the normal group, the volume, weight, anteroposterior diameter, left and right diameter, upper and lower diameters of brain tissue in the model group were decreased, and the difference was statistically significant. The results of HE staining showed that the cortical structure of normal group was clear, stratification was obvious, cells were arranged neatly, and no abnormal neurons were found. In the model group, the absence of corpus callosum, the enlargement of ventricle, the disorder of cortical structure, the disorder of polarity and density of neurons, the abnormal neurons and the nodules in the CA1 area of hippocampus were found in the model group. Conclusion: in this experiment, the MCD rat model was established successfully by the first generation of offspring of female mice irradiated with X ray of 1: 1195cGy. This method is simple and reliable. Rapamycin may decrease the incidence of epileptic waves in middle age MCD rats. Rapamycin has no significant effect on learning and memory ability of middle-aged MCD rats, and has no reverse effect on brain pathological damage.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R742.1

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