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放射性脑损伤对认知功能的影响及机制初探

发布时间:2019-01-17 08:47
【摘要】:【目的】初步探讨大鼠放射性脑损伤对认知功能的影响及发生机制。 【方法】11周左右SD大鼠(体重为250-290g)共160只,分别给予空白照射(n=20)、30Gy(n=70)、40Gy(n=70)左半脑照射,且以未经照射的对侧半球作为对照。每周检查照射区皮肤情况及体重变化;在照射后4周、12周、24周、36周通过MRI观察大鼠受照射侧大脑半球的影像学变化;在上述时间点取各组大鼠的脑组织进行HE染色,,观察海马区神经细胞的病理变化;LFB染色观察脱髓鞘变化;免疫组化使用CD31标记血管内皮细胞,检测血管密度的变化;NeuN标记海马区神经元;GFAP标记星形胶质细胞;分别于照射后24周、36周行Morris水迷宫检测大鼠的认知功能。 【结果】大鼠在放射性照射后4周开始出现照射野脱毛,同时照射组表现出体重的减轻,但体重的变化没有统计学意义;MRI显示在照射36周后海马及内囊位置出现明显的T2高信号征象;病理结果显示受照射的左半球可出现血管扩张、血管壁增厚、内皮细胞核增大、血栓形成及神经元固缩等表现,随着时间延长,可出现神经胶质细胞增生、脑室水肿及外囊中“格子细胞”形成。照射后36周时,海马伞、内囊处出现坏死(30Gy组=3/10,40Gy组=2/5)。照射后各时间点照射组脑白质中的LFB染色有不同程度的变化,但30Gy组和40Gy组在一定时期内(4w-36w)左侧和右侧均无显著性差异;36周时,40Gy剂量组左侧的髓鞘染色密度显著低于30Gy组左侧的髓鞘染色密度。CD31阳性细胞在30Gy组照射后12周、24周的结果示左侧明显低于右侧的细胞数目,40Gy组照射后24周、36周左侧显著高于右侧;30Gy剂量组在12周、36周时的左侧的血管密度都显著高于40Gy组。各时间点左侧海马成熟神经元(NeuN阳性细胞)的数目较右侧海马对照有不同程度的下降,两剂量组左侧的成熟神经元的数目之间只在4周时有差异。照射后各时间点GFAP阳性细胞左半球较右半球均有不同程度的增加,两剂量组左侧的数目之间无差异。Morris水迷宫实验在24周时,照射组与对照组大鼠穿起平台次数无显著性差异;在36周时,40Gy组大鼠较对照组穿越平台次数有显著性减少,同时,40Gy组大鼠较30Gy组穿越平台次数亦有显著性降低。 【结论】大鼠放射性脑损伤可以损害认知功能,同时有病理学、血管、胶质细胞、影像学的变化,并表现为剂量依赖性。
[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.
【学位授予单位】:华中科技大学
【学位级别】:硕士
【学位授予年份】:2013
【分类号】:R651.15

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1 陈大朝;陈龙华;金吴东;许乙凯;许鹏君;;放射性脑损伤的MRI诊断[J];中国现代医学杂志;2006年18期



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