【摘要】：【目的】初步探討大鼠放射性腦損傷對認知功能的影響及發(fā)生機制。 【方法】11周左右SD大鼠(體重為250-290g)共160只，分別給予空白照射（n=20）、30Gy（n=70）、40Gy（n=70）左半腦照射，且以未經(jīng)照射的對側(cè)半球作為對照。每周檢查照射區(qū)皮膚情況及體重變化；在照射后4周、12周、24周、36周通過MRI觀察大鼠受照射側(cè)大腦半球的影像學變化；在上述時間點取各組大鼠的腦組織進行HE染色，，觀察海馬區(qū)神經(jīng)細胞的病理變化；LFB染色觀察脫髓鞘變化；免疫組化使用CD31標記血管內(nèi)皮細胞，檢測血管密度的變化；NeuN標記海馬區(qū)神經(jīng)元；GFAP標記星形膠質(zhì)細胞；分別于照射后24周、36周行Morris水迷宮檢測大鼠的認知功能。 【結(jié)果】大鼠在放射性照射后4周開始出現(xiàn)照射野脫毛，同時照射組表現(xiàn)出體重的減輕,但體重的變化沒有統(tǒng)計學意義；MRI顯示在照射36周后海馬及內(nèi)囊位置出現(xiàn)明顯的T2高信號征象；病理結(jié)果顯示受照射的左半球可出現(xiàn)血管擴張、血管壁增厚、內(nèi)皮細胞核增大、血栓形成及神經(jīng)元固縮等表現(xiàn)，隨著時間延長，可出現(xiàn)神經(jīng)膠質(zhì)細胞增生、腦室水腫及外囊中“格子細胞”形成。照射后36周時，海馬傘、內(nèi)囊處出現(xiàn)壞死（30Gy組=3/10，40Gy組=2/5）。照射后各時間點照射組腦白質(zhì)中的LFB染色有不同程度的變化，但30Gy組和40Gy組在一定時期內(nèi)（4w-36w）左側(cè)和右側(cè)均無顯著性差異；36周時,40Gy劑量組左側(cè)的髓鞘染色密度顯著低于30Gy組左側(cè)的髓鞘染色密度。CD31陽性細胞在30Gy組照射后12周、24周的結(jié)果示左側(cè)明顯低于右側(cè)的細胞數(shù)目，40Gy組照射后24周、36周左側(cè)顯著高于右側(cè)；30Gy劑量組在12周、36周時的左側(cè)的血管密度都顯著高于40Gy組。各時間點左側(cè)海馬成熟神經(jīng)元（NeuN陽性細胞）的數(shù)目較右側(cè)海馬對照有不同程度的下降，兩劑量組左側(cè)的成熟神經(jīng)元的數(shù)目之間只在4周時有差異。照射后各時間點GFAP陽性細胞左半球較右半球均有不同程度的增加，兩劑量組左側(cè)的數(shù)目之間無差異。Morris水迷宮實驗在24周時，照射組與對照組大鼠穿起平臺次數(shù)無顯著性差異；在36周時，40Gy組大鼠較對照組穿越平臺次數(shù)有顯著性減少，同時，40Gy組大鼠較30Gy組穿越平臺次數(shù)亦有顯著性降低。 【結(jié)論】大鼠放射性腦損傷可以損害認知功能，同時有病理學、血管、膠質(zhì)細胞、影像學的變化，并表現(xiàn)為劑量依賴性。
[Abstract]:Objective: to explore the effect and mechanism of radiation brain injury on cognitive function in rats. [methods] 160 SD rats (body weight 250-290g) were exposed to blank irradiation (n = 20), 30Gy (n = 70), 40Gy (n = 70), and the contralateral hemisphere without irradiation for 11 weeks. The changes of skin and body weight in the irradiated area were examined weekly, and the imaging changes of the cerebral hemisphere of the irradiated side of the rats were observed through MRI at 4 weeks, 12 weeks, 24 weeks and 36 weeks after irradiation. At the above time points, the brain tissues of each group were stained with HE to observe the pathological changes of neurons in hippocampus, the changes of demyelinating by LFB staining, the changes of vascular endothelial cells labeled with CD31 by immunohistochemistry, and the changes of vascular density were detected by immunohistochemistry. Hippocampal neurons were labeled with NeuN and astrocytes were labeled with GFAP. The cognitive function of rats was measured by Morris water maze at 24 weeks and 36 weeks after irradiation. [results] hair loss in irradiation field began to occur in rats at 4 weeks after irradiation, and weight loss was observed in irradiation group, but the change of body weight was not statistically significant. After 36 weeks of irradiation, there were obvious T2 hyperintense signs in hippocampus and internal capsule on MRI. The pathological results showed that vascular dilatation, thickening of vascular wall, enlargement of endothelial nucleus, thrombosis and neuronal pyknosis appeared in the irradiated left hemisphere, and glial cell proliferation appeared with the prolongation of time. Ventricular edema and the formation of "lattice cells" in the outer capsule. At 36 weeks after irradiation, necrosis occurred in the hippocampal umbrella and internal capsule (30Gy group = 3 / 10 ~ 10 ~ 40 Gy group = 2 / 5). The changes of LFB staining in white matter were observed at different time points after irradiation, but there was no significant difference between 30Gy group and 40Gy group in left and right side (4w-36w). At 36 weeks, the density of myelin staining in the left side of 40Gy group was significantly lower than that in the left side of 30Gy group. The results of CD31 positive cells at 12 weeks and 24 weeks after irradiation in 30Gy group showed that the number of left side was significantly lower than that of right side, and that in 40Gy group was 24 weeks after irradiation. The left side was significantly higher than the right side at 36 weeks. The density of left blood vessels in 30Gy group was significantly higher than that in 40Gy group at 12 weeks and 36 weeks. The number of mature neurons (NeuN positive cells) in the left hippocampus at each time point was decreased to some extent than that in the right hippocampal control group, and the number of the mature neurons in the left side of the two dose groups was only different at 4 weeks. At each time point after irradiation, the number of GFAP positive cells in the left hemisphere was increased in different degrees compared with that in the right hemisphere, and there was no difference in the number of the left side between the two dose groups. At 24 weeks after irradiation, there was no significant difference in the number of perforations in the Morris water maze test between the irradiated group and the control group. At 36 weeks, the number of crossing platform in 40Gy group was significantly lower than that in control group, and the number of crossing platform in 40Gy group was significantly lower than that in 30Gy group. [conclusion] Radiation-induced brain injury may impair cognitive function and changes in pathology, blood vessels, glial cells and imaging in a dose-dependent manner.
【學位授予單位】：華中科技大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R651.15

【參考文獻】

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1 陳大朝;陳龍華;金吳東;許乙凱;許鵬君;;放射性腦損傷的MRI診斷[J];中國現(xiàn)代醫(yī)學雜志;2006年18期

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