电离辐射抑制海马区神经发生与小鼠放射性脑损伤认知损害关系的研究

发布时间：2018-12-17 20:18

【摘要】：【目的】研究放疗后海马区神经发生改变与小鼠放射性脑损伤认知损害的关系。【方法】10天龄C57BL/6J小鼠，给予10Gy全脑照射，Morris水迷宫实验检测放射性脑损伤模型的建立；在照射后不同时间点取脑组织标本进行HE染色，观察海马区神经细胞的病理变化；免疫组化染色DCX、PCNA标记海马区神经发生水平；ED1标记小胶质细胞激活情况；TUNEL标记海马区神经细胞凋亡情况；γ-H2AX免疫荧光染色标记DSB形成情况；Real-time PCR检测脑组织TNF-、IL-1β表达水平的变化；ELISA检测照射后不同时间点血浆TNF-水平的变化。【结果】放疗后急性期表现为间质水肿，炎症细胞浸润，海马区齿状回神经细胞逐渐出现变性、坏死、凋亡，慢性期间质水肿消退，炎症细胞减少，海马齿状回出现细胞再生呈极性分布；照射后各时间点DCX阳性细胞和PCNA阳性细胞较对照组均有不同程度减少；照射后ED1阳性细胞较对照组增多；TUNEL标记凋亡神经元在放疗后6小时可见，于48小时达到峰值；照射后0.5小时γ-H2AX焦点形成达到高峰，，后逐渐减少；照射后脑组织TNF-、IL-1β表达较对照组均有所增加；血浆TNF-照射后3小时开始升高，至1周时达到峰值，随后逐渐降低；Morris水迷宫实验照射组和对照组相比，在实验第1、2、3天两者成绩无明显差异，但随着时间延长第4、5、6天照射组躲避潜伏期较对照组延长。【结论】10Gy全脑照射后建立放射性脑损伤模型，并发现海马区神经发生受到抑制和小胶质细胞激活，这可能是小鼠放射性脑损伤认知损害产生的原因之一。
[Abstract]:Objective: to study the relationship between the changes of hippocampal nerve after radiotherapy and cognitive impairment of radiation brain injury in mice. [methods] 10-day-old C57BL/6J mice were exposed to 10Gy whole brain irradiation, and Morris water maze test was used to detect the establishment of radiation-induced brain injury model. Brain tissue samples were taken at different time points after irradiation for HE staining to observe the pathological changes of hippocampal neurons. DCX,PCNA labeled hippocampal neurogenesis level, ED1 labeled microglia activation, TUNEL labeled hippocampal neuronal apoptosis, 纬-H2AX immunofluorescence staining labeled DSB formation; Real-time PCR was used to detect the expression of TNF-,IL-1 尾 in brain and ELISA was used to detect the changes of plasma TNF- at different time points after irradiation. [results] in the acute stage after radiotherapy, interstitial edema, inflammatory cell infiltration, degeneration, necrosis, apoptosis, receding of chronic edema and decrease of inflammatory cells were observed in dentate gyrus of hippocampus. Cell regeneration in dentate gyrus of sea horse showed polar distribution. The number of DCX positive cells and PCNA positive cells decreased in different degrees after irradiation, the number of ED1 positive cells increased after irradiation, and the apoptotic neurons labeled with TUNEL reached the peak at 48 hours after radiotherapy. The focal point formation of 纬-H2AX reached the peak at 0. 5 h after irradiation, and then decreased gradually, and the expression of TNF-,IL-1 尾 in brain tissue increased after irradiation compared with the control group. Plasma TNF- began to rise at 3 hours after irradiation, reached its peak at 1 week, and then decreased gradually. There was no significant difference between the Morris water maze exposure group and the control group on the 3rd day of the experiment, but the escape latency of the exposure group was longer than that of the control group on the 4th day and 6th day with the extension of time. [conclusion] Radiation-induced brain injury model was established after 10Gy whole brain irradiation, and it was found that hippocampal neurogenesis was inhibited and microglia activated, which may be one of the causes of cognitive impairment caused by radiation brain injury in mice.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R818

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