KLF4在伽马刀照射所致大鼠放射性脑损伤中的作用机制

Study on role of KLF4 in radiation-induced brain injury of rats caused by gamma knife irradiation

目的研究伽马刀立体定向照射大鼠正常脑组织后星形胶质细胞中KLF4及γ-H2AX随照射剂量变化的表达,探讨KLF4与放射性脑损伤的关系。方法成年雄性Wistar大鼠30只,按随机数字表法分为6组,每组5只,分别以不同照射剂量(0、10、20、30、40、50 Gy)照射大鼠右侧尾壳核,照射30 min后处死,并分析不同照射剂量下KLF4、γ-H2AX阳性细胞占星形胶质细胞的百分比,分析KLF4和γ-H2AX的表达与照射剂量之间、KLF4与γ-H2AX之间的线性回归关系。结果 KLF4、γ-H2AX阳性细胞占星形胶质细胞的百分比随照射剂量增加而上升(P<0.05),且KLF4、γ-H2AX的表达与照射剂量、KLF4与γ-H2AX均有显著线性关系(P<0.05)。结论 KLF4与辐射所致大鼠脑星形胶质细胞DNA双链损伤关系密切,其可能是辐射致DNA损伤的关键分子,通过引起DNA双链损伤导致放射性脑损伤。

Objective To investigate the dose-related expression of KLF4 and γ-H2AX in the normal rat brain after gamma knife irradiation, and to discuss the relationship between KFL4 and brain radiation injury. Methods Thirty adult male Wistar rats were divided into 6 groups according to the random digits table ,five rats in each group. The right caudate-putamen nu- cleus was irradiated at different dosage of exposure of gamma knife irradiation （0,10,20,30,40 and 50 Gy）. Rats were sacrificed at 30 minutes after irradiation,both the percentage of KLF4 and γ-H2AX positive cells on the total astrocytes were calculated, and the linear regression relationships between the percentage of KLF4 positive cells and the radiation dosage, the percentage of γ-H2AX positive cells and the radiation dosage, and the percentage of KLF4 positive cells and that of the γ-H2AX positive cells were analyzed separately. Results Both the percentage of KLF4 and γ-H2AX positive cells were increased following the increas- ing irradiation dosage（ P 〈 0.05 ）, and the linear relationships between the KLF4 and the irradiation dosage,the γ-H2AX and the radiation dosage, and the KLF4 and the γ-H2AX were significant （P 〈 0.05 ）. Conclusion KLF4 has a close relationship with the double-stranded DNA damage caused by irradiation in the brain astrocytes of rats. It could be the key molecule in the DNA damage induced by radiation ,which could finally lead to radiation-induced brain injury.