本文選題：蛛網(wǎng)膜下腔出血 + 腦脊液�。� 參考：《河北醫(yī)科大學(xué)》2017年博士論文

【摘要】：蛛網(wǎng)膜下腔出血(Subarachnoid hemorrhage,SAH),是一種臨床常見的危重病癥,泛指腦底部或腦表面的病變血管破裂,血液直接流入蛛網(wǎng)膜下腔引起的一種臨床綜合征。根據(jù)出血部位和出血量的不同,治療效果差異很大。SAH常見的并發(fā)癥有,再出血、腦血管痙攣和急慢性腦積水(hydrocephalus)等。有些SAH的幸存者,可出現(xiàn)進(jìn)行性腦室增大、腦皮質(zhì)萎縮和認(rèn)知功能障礙甚至變得癡呆。阿爾茲海默病(Alzheimer's disease)簡稱AD,又稱早老性或老年性癡呆,是臨床上最為常見的癡呆類型。相繼的研究發(fā)現(xiàn),它是一種以進(jìn)行性學(xué)習(xí)、記憶和認(rèn)知功能障礙為主要臨床表現(xiàn)的神經(jīng)退行性疾病;目前對其發(fā)病機(jī)制仍不十分清楚,也無明確有效的防治方法。我們好奇,是否這種SAH后遺癥的發(fā)生,與AD的發(fā)生和發(fā)展存在相似的病理機(jī)制?眾所周知,正常的腦脊液(Cerebrospinal fluid,CSF)循環(huán),對于腦組織代謝產(chǎn)物,尤其是脂質(zhì)、蛋白等大分子物質(zhì)的轉(zhuǎn)運(yùn),維持中樞神經(jīng)系統(tǒng)內(nèi)環(huán)境的相對穩(wěn)定,發(fā)揮著難以替代的作用。所以有理由推測,是否由于不同原因引起的慢性CSF循環(huán)障礙或腦積水,導(dǎo)致了腦組織代謝產(chǎn)物轉(zhuǎn)運(yùn)異常,誘發(fā)了腦組織出現(xiàn)病理性變化和功能受損?本研究模擬蛛網(wǎng)膜下腔出血,建立慢性CSF循環(huán)障礙的大鼠模型,觀察和檢測實(shí)驗(yàn)動物的行為變化、海馬皮質(zhì)神經(jīng)細(xì)胞內(nèi)線粒體跨膜電位、以及海馬皮質(zhì)、側(cè)腦室室管膜和脈絡(luò)叢的細(xì)微和超微結(jié)構(gòu)變化,檢測海馬皮質(zhì)內(nèi)相關(guān)蛋白表達(dá)的變化等。本實(shí)驗(yàn)研究分為以下三部分。第一部分實(shí)驗(yàn)性蛛網(wǎng)膜下腔出血大鼠模型的建立和對其行為影響的觀察目的:本部分研究實(shí)驗(yàn)性蛛網(wǎng)膜下腔出血(SAH)繼發(fā)的腦損傷,對大鼠認(rèn)知功能產(chǎn)生的傷害性影響,為實(shí)驗(yàn)性SAH對海馬皮質(zhì)、側(cè)腦室室管膜以及脈絡(luò)叢損傷機(jī)制的研究,提供行為學(xué)證據(jù)。方法:選取成年SD大鼠60只,平均體重為300.40±44.50 g,雌雄不拘;將60只大鼠隨機(jī)分為試驗(yàn)組和對照組,各組30只。試驗(yàn)組大鼠用10%的水合氯醛進(jìn)行腹腔注射麻醉后,向腦枕大池(或稱小腦延髓池)內(nèi)注入自體動脈血0.30 ml,制作模擬SAH的實(shí)驗(yàn)動物模型;對照組大鼠只是向枕大池內(nèi)注射等量生理鹽水,其余操作步驟同試驗(yàn)組。同時(shí),對試驗(yàn)組和對照組大鼠(各10只),術(shù)后進(jìn)行常規(guī)喂養(yǎng),并于術(shù)后2個(gè)月、4個(gè)月、6個(gè)月時(shí),進(jìn)行一般行為學(xué)統(tǒng)計(jì)分析、神經(jīng)功能整體評分和行為學(xué)研究三個(gè)方面的測試,統(tǒng)計(jì)和分析相關(guān)數(shù)據(jù)。結(jié)果:與對照組相比,試驗(yàn)組大鼠術(shù)后出現(xiàn)精神萎靡不振、嗜睡、飲食減少,肢體活動力減低等神經(jīng)功能缺損的表現(xiàn),P0.05,差異具有統(tǒng)計(jì)學(xué)意義;并且隨著飼養(yǎng)時(shí)間的延長,這種現(xiàn)象更加明顯,P0.05,差異具有統(tǒng)計(jì)學(xué)意義;在Morris水迷宮試驗(yàn)的測試中,與對照組相比,試驗(yàn)組大鼠的空間學(xué)習(xí)能力以及記憶能力明顯下降,P0.05,差異具有統(tǒng)計(jì)學(xué)意義;并且隨著飼養(yǎng)月份的延長,試驗(yàn)組大鼠的學(xué)習(xí)、記憶、認(rèn)知功能和活動能力逐漸減退,P0.05,差異具有統(tǒng)計(jì)學(xué)意義。第二部分實(shí)驗(yàn)性蛛網(wǎng)膜下腔出血誘發(fā)大鼠海馬皮質(zhì)和側(cè)腦室室管膜及脈絡(luò)叢的形態(tài)學(xué)變化目的:本部分研究主要通過光鏡、電鏡和流式細(xì)胞術(shù),觀察實(shí)驗(yàn)性蛛網(wǎng)膜下腔出血(SAH),誘發(fā)大鼠海馬皮質(zhì)、側(cè)腦室室管膜及脈絡(luò)叢的形態(tài)學(xué)變化,海馬皮質(zhì)神經(jīng)細(xì)胞內(nèi)線粒體跨膜電位(MTP)的變化,為實(shí)驗(yàn)性SAH對大鼠海馬皮質(zhì)、側(cè)腦室室管膜及脈絡(luò)叢的損傷機(jī)制,提供實(shí)驗(yàn)形態(tài)學(xué)證據(jù)。方法:選取成年SD大鼠90只,平均體重為300.20±27.50 g,雌雄不拘;將90只大鼠隨機(jī)分為試驗(yàn)組和對照組,每組各45只。試驗(yàn)組大鼠用10%的水合氯醛進(jìn)行腹腔注射麻醉后,向腦枕大池內(nèi)注入其自體動脈血液0.30 ml,制作模擬SAH的實(shí)驗(yàn)動物模型;對照組大鼠只是向枕大池內(nèi)注射等量生理鹽水,其余操作步驟同試驗(yàn)組。試驗(yàn)組和對照組大鼠(各取10只)術(shù)后進(jìn)行常規(guī)喂養(yǎng),并于術(shù)后2個(gè)月、4個(gè)月、6個(gè)月時(shí),通過主動脈灌注固定取材,進(jìn)行光鏡、掃描和透射電鏡樣品的制備;同時(shí)每組隨機(jī)取5只大鼠,通過深度麻醉下斷頭取腦的方法剝離雙側(cè)海馬,應(yīng)用流式細(xì)胞術(shù)檢測海馬皮質(zhì)神經(jīng)細(xì)胞內(nèi)MTP;通過熒光顯微鏡拍照,觀察海馬皮質(zhì)神經(jīng)細(xì)胞的凋亡情況;比較試驗(yàn)組與對照組大鼠海馬皮質(zhì)、側(cè)腦室室管膜及脈絡(luò)叢,在光鏡、掃描和透射電鏡下的細(xì)微和超微結(jié)構(gòu)差異,以及兩組大鼠海馬皮質(zhì)神經(jīng)細(xì)胞內(nèi)MTP的差異,揭示實(shí)驗(yàn)性SAH對大鼠相關(guān)腦組織結(jié)構(gòu)的影響,為行為變化提供形態(tài)學(xué)依據(jù)。結(jié)果:試驗(yàn)組:光鏡觀察顯示,隨著術(shù)后飼養(yǎng)月份的增加,大鼠側(cè)腦室逐漸增大,室管膜細(xì)胞由立方形變?yōu)槎嘈涡陨踔帘馄叫?海馬皮質(zhì)表面的室管膜結(jié)構(gòu)出現(xiàn)細(xì)微改變,在海馬槽和多形細(xì)胞層,可觀察到小血管周圍間隙明顯增寬,錐體細(xì)胞層明顯變薄,細(xì)胞數(shù)量減少,細(xì)胞排列紊亂;并且,飼養(yǎng)時(shí)間越長,這種現(xiàn)象越明顯。掃描電鏡觀察顯示,在脈絡(luò)叢上皮細(xì)胞表面,出現(xiàn)大量火山口樣凹陷,其絨毛萎縮、扭曲甚至脫落;在海馬皮質(zhì)被覆的室管膜細(xì)胞表面,其纖毛和微絨毛明顯減少。透射電鏡觀察顯示,脈絡(luò)叢上皮細(xì)胞可見大量的吞飲泡,胞體和胞核呈現(xiàn)不規(guī)則狀;海馬皮質(zhì)錐體細(xì)胞核內(nèi)的異染色質(zhì)明顯增多,細(xì)胞內(nèi)出現(xiàn)膨大的線粒體、神經(jīng)原纖維纏結(jié)的團(tuán)塊,在神經(jīng)氈內(nèi)的淀粉樣脂蛋白沉積等現(xiàn)象;在術(shù)后飼養(yǎng)到6個(gè)月時(shí),這種現(xiàn)象更為明顯;表現(xiàn)為海馬室管膜細(xì)胞表面的微絨毛減少更明顯,大量的淀粉樣脂蛋白沉積在血管周圍。JC-1流式細(xì)胞術(shù)檢測發(fā)現(xiàn),海馬皮質(zhì)神經(jīng)細(xì)胞內(nèi)MTP去極化現(xiàn)象嚴(yán)重,與對照組相比,P0.05,差異具有統(tǒng)計(jì)學(xué)意義,提示神經(jīng)細(xì)胞內(nèi)線粒體發(fā)生不同程度的病理變化,細(xì)胞凋亡現(xiàn)象明顯;并且隨著飼養(yǎng)時(shí)間的延長,這種現(xiàn)象逐漸加重,P0.05,差異具有統(tǒng)計(jì)學(xué)意義。然而在對照組:術(shù)后2個(gè)月、4個(gè)月甚至6個(gè)月,大鼠的海馬皮質(zhì)、側(cè)腦室室管膜及脈絡(luò)叢,以及海馬皮質(zhì)神經(jīng)細(xì)胞內(nèi)MTP,均未觀察到明顯的病理變化。第三部分實(shí)驗(yàn)性蛛網(wǎng)膜下腔出血大鼠海馬皮質(zhì)內(nèi)炎性和自噬相關(guān)蛋白表達(dá)的變化目的:以上述兩部分的研究為基礎(chǔ),通過免疫組織化學(xué)法、Western blot以及TUNEL檢測法,進(jìn)一步探討實(shí)驗(yàn)性蛛網(wǎng)膜下腔出血(SAH),對大鼠與學(xué)習(xí)、記憶相關(guān)的重要腦區(qū)—海馬皮質(zhì)內(nèi)炎性和自噬相關(guān)蛋白表達(dá)的影響,揭示實(shí)驗(yàn)性SAH與AD之間的關(guān)聯(lián)性。方法:選取成年SD大鼠90只,平均體重為289.40±45.50 g,雌雄不拘;隨機(jī)將大鼠分為試驗(yàn)組和對照組,每組各45只。試驗(yàn)組大鼠用10%的水合氯醛進(jìn)行腹腔注射麻醉后,向枕大池內(nèi)注入自體動脈血0.30 ml,制作模擬SAH的實(shí)驗(yàn)動物模型;對照組大鼠只是向枕大池內(nèi)注射等量生理鹽水,其余操作步驟同試驗(yàn)組。同時(shí),對試驗(yàn)組和對照組大鼠進(jìn)行常規(guī)喂養(yǎng),并于術(shù)后2個(gè)月、4個(gè)月、6個(gè)月時(shí),隨機(jī)每組取10只大鼠,經(jīng)主動脈灌注固定取材,石蠟切片,通過免疫組織化學(xué)染色法,觀察Aβ,IL-1β,IBA-1在海馬皮質(zhì)的表達(dá)情況;采用TUNEL檢測法,觀察大鼠海馬皮質(zhì)錐體細(xì)胞的凋亡情況。同時(shí)隨機(jī)每組取5只大鼠,在深度麻醉下快速斷頭取腦,剝離大鼠雙側(cè)海馬皮質(zhì)結(jié)構(gòu),通過Western blot法,檢測炎性相關(guān)蛋白IL-1β、自噬相關(guān)蛋白(Atg-5,Beclin-l和LC-3),在大鼠海馬皮質(zhì)的表達(dá);記錄并分析相關(guān)數(shù)據(jù)。結(jié)果:1 Western blot結(jié)果分析:與對照組相比,試驗(yàn)組大鼠海馬皮質(zhì)炎性相關(guān)蛋白IL-1β、自噬相關(guān)蛋白(Atg-5,Beclin-l和LC-3)的表達(dá)明顯增多,P0.05,差異具有統(tǒng)計(jì)學(xué)意義;并且隨著術(shù)后飼養(yǎng)時(shí)間的延長表達(dá)呈現(xiàn)上升趨勢,P0.05,差異具有統(tǒng)計(jì)學(xué)意義。2免疫組織化學(xué)結(jié)果顯示:與對照組相比,試驗(yàn)組大鼠在實(shí)驗(yàn)性SAH術(shù)后,海馬皮質(zhì)內(nèi)Aβ、IL-1β、IBA-1的表達(dá)明顯增多,并且隨著術(shù)后飼養(yǎng)時(shí)間的延長呈現(xiàn)上升趨勢。3 TUNEL檢測結(jié)果表明:在實(shí)驗(yàn)性SAH術(shù)后,與對照組相比,試驗(yàn)組大鼠的海馬皮質(zhì)內(nèi)錐體細(xì)胞凋亡現(xiàn)象增多,P0.05,差異具有統(tǒng)計(jì)學(xué)意義,并且隨著術(shù)后飼養(yǎng)時(shí)間的延長而逐漸加重,術(shù)后飼養(yǎng)6個(gè)月時(shí)達(dá)高峰,P0.05,差異具有統(tǒng)計(jì)學(xué)意義。結(jié)論:1采用枕大池單次注射微量自體動脈血的方法,可以成功復(fù)制模擬SAH的實(shí)驗(yàn)大鼠模型,其病理變化與行為表現(xiàn)相一致,具有較為可靠的基礎(chǔ)和臨床研究參考意義。2實(shí)驗(yàn)性SAH可導(dǎo)致試驗(yàn)組大鼠的學(xué)習(xí)、記憶以及活動能力明顯減退,并且隨著術(shù)后飼養(yǎng)時(shí)間的延長,病情逐漸加重;提示實(shí)驗(yàn)性SAH可能對大鼠側(cè)腦室室管膜、脈絡(luò)叢、海馬皮質(zhì)等結(jié)構(gòu),造成了不同程度的病理性損傷。3實(shí)驗(yàn)性SAH可誘發(fā)大鼠海馬皮質(zhì)、側(cè)腦室室管膜以及脈絡(luò)叢的細(xì)微和超微結(jié)構(gòu)變化,誘發(fā)海馬皮質(zhì)神經(jīng)細(xì)胞內(nèi)MTP去極化,出現(xiàn)神經(jīng)細(xì)胞凋亡或壞死增多現(xiàn)象。4實(shí)驗(yàn)性SAH可誘發(fā)大鼠海馬皮質(zhì)炎性因子表達(dá)增高、細(xì)胞自噬作用增強(qiáng),淀粉樣脂蛋白沉積,以及海馬皮質(zhì)錐體細(xì)胞凋亡等現(xiàn)象,并且隨著術(shù)后飼養(yǎng)時(shí)間的延長,愈發(fā)嚴(yán)重。
[Abstract]:Subarachnoid hemorrhage (SAH) is a common and critically ill disease. It refers to a clinical syndrome caused by the rupture of the vessels at the base of the brain or the surface of the brain and the blood flow directly into the subarachnoid cavity. According to the site of bleeding and the amount of bleeding, there are many common complications in the treatment of.SAH. Blood, cerebral vasospasm, and acute and chronic hydrocephalus (hydrocephalus). Some of the survivors of SAH have progressive ventricular enlargement, cortical atrophy and cognitive impairment or even dementia. Alzheimer's disease (Alzheimer's disease), referred to as premature or senile dementia, is the most common type of dementia in clinical. It has been found that it is a neurodegenerative disease with progressive learning, memory and cognitive impairment as the main clinical manifestation. The pathogenesis is still not very clear, and there is no clear and effective method of prevention and control. We wonder if this SAH sequela is similar to the occurrence and development of AD. It is known that the normal Cerebrospinal fluid (CSF) cycle is difficult to substitute for the transport of brain tissue metabolites, especially lipid, protein and other macromolecular substances, to maintain the relative stability of the central nervous system. Therefore, there is reason to speculate on the chronic CSF circulation disorder or brain caused by different causes. Water accumulation has caused abnormal transport of brain tissue metabolites and induced pathological changes and functional impairment of brain tissue. This study simulated subarachnoid hemorrhage, established a rat model of chronic CSF circulation disorder, observed and detected behavioral changes in experimental animals, mitochondrial transmembrane potential in the hippocampus, and the cortex and side of the hippocampus. Changes in the ultrastructure of the ventricular ependyma and choroid plexus and the changes in the expression of related proteins in the cortex of the hippocampus were detected. The study was divided into three parts. The first part of the experiment was to establish and observe the effects of the experimental subarachnoid hemorrhage model in rats: this part studies experimental subarachnoid hemorrhage (SAH). The effects of secondary brain injury on the cognitive function of rats, and the behavioral evidence for the study of the damage mechanism of the hippocampal cortex, the lateral ventricular ependyma and choroid plexus in the experimental SAH. Methods: 60 adult SD rats were selected, the average weight was 300.40 + 44.50 g, and the female male was not restricted. The rats were randomly divided into the experimental group and the control group. After intraperitoneal injection of 10% chloral chloral, the rats in the experimental group were injected with 0.30 ml of autologous arterial blood into the big pool of the brain occipital (or cerebellopontine medullary pool) to make an experimental animal model for simulating SAH. The control group was only injected with the same amount of normal saline in the large cistern, the rest of the operation were the same as the experimental group. At the same time, the experimental group and the test group were used in the control group. Rats in the control group (10 rats each) were fed with regular feeding after operation, and 2 months, 4 months and 6 months after the operation, the general behavioral statistical analysis, the overall neurological score and the behavioral study were tested in three aspects, and the related data were analyzed. Results: compared with the control group, the rats in the experimental group were depressed, drowsiness, drinking. P0.05, the difference has statistical significance, and with the prolongation of feeding time, the difference has statistical significance. In the test of the Morris water maze test, the spatial learning ability and memory ability of the rats in the test group were compared with the control group. The difference was statistically significant in P0.05, and with the prolongation of the feeding month, the learning, memory, cognitive function and activity ability of rats in the experimental group gradually decreased, and the difference was statistically significant. The second part of experimental subarachnoid hemorrhage induced the morphology of the cortex and lateral ventricular ependyma and choroid plexus in the hippocampus of rats. Objective: To observe the morphological changes of the hippocampal cortex, the ependyma and choroid plexus of the rats, the changes in the mitochondrial transmembrane potential (MTP) in the hippocampal neurons of the hippocampus, and the experimental SAH to the hippocampus and the lateral ventricle of the rat, mainly through the observation of the experimental subarachnoid hemorrhage (SAH) by light microscopy, electron microscopy and flow cytometry. The damage mechanism of ependyma and choroid plexus was provided with experimental morphological evidence. Methods: 90 adult SD rats, with an average weight of 300.20 + 27.50 g, were randomly divided into experimental and control groups, which were randomly divided into experimental and control groups, with 45 rats in each group. The rats in the experimental group were injected with 10% chloral chloral anesthesia and injected into the large cerebral cisterns. The blood of the body artery was 0.30 ml, and the experimental animal model of the simulated SAH was made. The rats in the control group were only injected with the same amount of saline in the large cistern, the rest of the operation were the same as the experimental group. The experimental group and the control group (each taken from each group) were given routine feeding after the operation, and the material was fixed by the aorta for 2 months, 4 months and 6 months after the operation. The samples of microscope, scanning and transmission electron microscope were prepared. At the same time, 5 rats in each group were randomly taken from each group. The bilateral hippocampus was stripped by the method of head extraction under deep anesthesia. Flow cytometry was used to detect the MTP in the hippocampal neurons. The apoptosis of the hippocampus was observed by the fluorescence microscope, and the experimental group and the control group were compared. Hippocampal cortex, lateral ventricle ependyma and choroid plexus, microscopic and ultrastructural differences under light microscopy, scanning and transmission electron microscopy, and the difference of MTP in the hippocampal neurons of two groups of rats, reveal the effects of experimental SAH on the brain tissue structure of rats, and provide morphological basis for behavioral changes. Results: experimental group: light microscope observation showed that With the increase of the month after the operation, the lateral ventricle of the rat gradually increased. The ependymal cells were formed from cubic deformation to pleomorphic or even flat shape, and the ependymal membrane structure of the hippocampal cortical surface changed slightly. In the hippocampal groove and the multiform cell layer, the space around the small vessels was obviously widened, the pyramidal cell layer became thinner and the number of cells decreased. Cells were arranged in disorder; and the longer the feeding time, the more obvious the phenomenon was. A large number of crater like sags appeared on the surface of the choroid plexus epithelial cells, and its villi atrophied, twisted and even dropped off, and its cilia and microvilli decreased significantly on the surface of the ependymal cells covered by the hippocampal cortex. Transmission electron microscopy showed that veins The epithelial cells of the collaterals showed a large number of swallowing vesicles and irregular shape of the cell and nucleus; the heterochromatin in the pyramidal nucleus of the hippocampal cortex increased obviously, the cells appeared expanded mitochondria, the neurofibrillary clumps, and the amyloid lipoprotein deposition in the felt; after 6 months of rearing, this phenomenon was more important. Obviously, the decrease of microvilli on the surface of the hippocampal ependymal cells was more obvious. A large number of amyloid lipoproteins were detected by.JC-1 flow cytometry around the vessels, and the MTP depolarization in the hippocampal neurons was serious. Compared with the control group, the difference was statistically significant, suggesting that the mitochondria in the nerve cells were different. In the control group, the hippocampus, the lateral ventricular ependyma and the choroid plexus, and the MTP in the hippocampal neurons were not observed in the control group for 2 months, 4 months or even 6 months after the operation. Obvious pathological changes. The changes in the expression of inflammatory and autophagy related proteins in the hippocampal cortex in third experimental subarachnoid hemorrhage rats: Based on the two parts of the above study, the experimental subarachnoid hemorrhage (SAH) was further explored by immunohistochemistry, Western blot and TUNEL detection. The relationship between the inflammatory and autophagy related protein expression in the hippocampal cortex was studied. Methods: the relationship between experimental SAH and AD was revealed. Methods: 90 adult SD rats were selected, the average weight was 289.40 + 45.50 g, and the male and female were not restricted. The rats were randomly divided into experimental group and control group, 45 rats in each group. The rats in the experimental group were hydrated with 10% hydration. After intraperitoneal injection of chloral anaesthesia, 0.30 ml of autologous arterial blood was injected into the large cistern to make an experimental animal model of simulated SAH. The control group was only injected with the same amount of saline in the large cistern, the rest of the operation were the same as the experimental group. At the same time, the experimental group and the control group were routinely fed, and 2 months, 4 months, and 6 months after the operation. At random, 10 rats in each group were taken at random. The expression of A beta, IL-1 beta and IBA-1 in the hippocampus was observed by immunohistochemical staining. The apoptosis of hippocampal pyramidal cells in the hippocampus of rats was observed by TUNEL detection. At the same time, 5 rats in each group were taken to quickly break the head under deep anesthesia. Take the brain and peel off the hippocampal cortex structure in rats and detect the expression of inflammatory related protein IL-1 beta, autophagy related protein (Atg-5, Beclin-l and LC-3) in the hippocampus cortex of rats by Western blot method, and record and analyze the related data. Results: 1 Western blot results were analyzed: compared with the control group, the inflammatory related protein IL- in the hippocampus cortex of the experimental group was compared with the control group. The expression of 1 beta, autophagy related proteins (Atg-5, Beclin-l and LC-3) was significantly increased, P0.05, and the difference was statistically significant. And with the extension of postoperative feeding time, the expression of the protein showed an upward trend, P0.05, the difference was statistically significant,.2 immunohistochemical results showed that compared with the control group, the experimental group was in the hippocampus cortex after the experimental SAH operation. The expression of A beta, IL-1 beta, and IBA-1 increased significantly, and increased with the increase of post operation feeding time.3 TUNEL results showed that after experimental SAH, the pyramidal cell apoptosis in the hippocampus of the experimental group increased, and the difference of P0.05 was statistically significant compared with the control group, and with the postoperative feeding time. The difference has statistical significance at 6 months after operation, and the difference has statistical significance at 6 months after operation. Conclusion: 1 the experimental rat model of simulated SAH can be successfully replicated by single injection of micro autologous arterial blood in the occipital big pool. The pathological changes are in accordance with the behavior expression, which has a more reliable basis and clinical reference significance.2. Experimental SAH could lead to the learning, memory, and activity of rats in the experimental group, and the condition was gradually increased with the prolongation of the feeding time. It suggested that the experimental SAH may cause the lateral ventricular ependyma, choroid plexus, and the hippocampal cortex in rats, causing different degrees of pathological damage to.3 experimental SAH can induce the rat sea. The fine and ultrastructural changes in the horse cortex, the lateral ventricular ependyma and choroid plexus, induced MTP depolarization in the hippocampal neurons, apoptosis or necrosis of the neurons,.4 experimental SAH can induce the increased expression of inflammatory factors in the hippocampus, the enhancement of autophagy, the deposition of amyloid lipoprotein, and the cortex of the hippocampus Pyramidal cell apoptosis and other phenomena, and with the extension of postoperative feeding time, more serious.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R743.35

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