电离辐射对幼鼠小脑和前额叶皮质发育的影响

Effects of ionizing radiation on the development of cerebellum and prefrontal cortex in mice during neonatal period

为探讨X射线对幼鼠小脑和前额叶皮质发育的影响,照射组小鼠于出生后(postanal day,PD)3天进行2 Gy(2 Gy/min)剂量的全身X射线照射,分别于照射后7、21和90天(PD 3+7、PD 3+21、PD 3+90)采集脑样本进行不同的实验研究。苏木素-伊红(Hematoxylin-eosin,HE)染色检测脑组织病理形态变化,免疫组织化学检测IBa1和GFAP蛋白表达,Western Blotting检测IL-1β和TNF-α蛋白表达。结果表明,照射组小脑及前额叶皮质炎性细胞浸润,外颗粒层厚度变窄,浦肯野细胞向内颗粒层迁移,小脑部分细胞丢失。与对照组比较,照射后21天小脑IBa1阳性细胞数增加(p<0.05),照射后7天GFAP阳性细胞数减少(p<0.05)。前额叶皮质中IBa1阳性细胞在照射后数量持续增加(p<0.05,p<0.01),GFAP阳性细胞数量持续减少(p<0.01)。照射后90天,小鼠小脑和前额叶皮质中IL-1β蛋白表达均增加(p<0.05),而TNF-α表达无改变。结果证实幼年小鼠2 Gy X射线照射可引起小鼠小脑颗粒细胞层、分子层、浦肯野细胞层产生连续性病理改变,前额叶皮质出现炎性细胞聚集,前额叶皮质和小脑小胶质细胞数量增加,星形胶质细胞数量减少,炎症因子主要是IL-1β。

To investigate the effects of X-ray on the development of cerebellum and prefrontal cortex in mice during neonatal period,the mice in irradiation group were irradiated with whole-body X-ray dose of 2 Gy(2 Gy/min)at the postanal day 3(PD 3).Irradiated mice were euthanized at 7,21 and 90 days after irradiation(PD 3+7,PD 3+21,PD 3+90)and brain samples were collected for different experimental studies.Hematoxylin-eosin(HE)was utilized to detect the pathomorphological changes of brain tissue;Immunohisto-chemistry were used to detect the protein expression of IBa1 and GFAP;Western blotting were used to detect the protein expression of IL-1βand TNF-α.In the irradiation group,the inflammatory cell infiltration was observed in the cerebellum and prefrontal cortex,and the thickness of external granular layer(EGL)narrowed.Purkinje cells migrated to internal granular layer(IGL)and some cells were lost in the cerebellum.Compared with the control group,the number of IBa1 positive cells increased at 21 days after irradiation(p<0.05),while the number of GFAP positive cells decreased at 7 days after irradiation in cerebellum(p<0.05).The number of IBa1 positive cells continued to increase until adulthood(p<0.05,p<0.01),and the number of GFAP positive cells continued to decrease until adulthood in prefrontal cortex(p<0.01).The protein expression of IL-1βincreased at 90 days after radiation in cerebellum and prefrontal cortex(p<0.05),while the expression of TNF-αdid not change.Neonatal exposure to 2 Gy X-ray caused continuous pathological changes in the granulosa cell layer,molecular layer and Purkinje cell layer of cerebellum,and inflammatory cell aggregation in the prefrontal cortex.Neonatal exposure to 2 Gy X-ray increased the number of microglia in the prefrontal cortex and cerebellum,decreased the number of astrocytes.IL-1βis mainly the inflammatory factor.