Shenqi Fuzheng Injection attenuates irradiation- induced brain injury in mice via inhibition of the NF-κB signaling pathway and microglial activation  

作　　者：Jian ZHANG Fan TONG Qian CAI Ling-juan CHEN Ji-hua DONG Gang WU Xiao-rong DONG 

机构地区：[1]Cancer Center, Wuhan430022, China [2]Experimental Center, Union Hospital, Tongl'i Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

出　　处：《Acta Pharmacologica Sinica》2015年第11期1288-1299,共12页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by grants from the National Natural Science Foundation of China （81573090 and 81172595）, Postdoctor Foundation of China （20100480905）, Post-doctor Special Foundation of China （201104440）, and China Oncology Clinical Science Fund （Y-L2011-002）.

摘　　要：Aim： Radiation-induced brain injury （RIBI） is the most common and severe adverse effect induced by cranial radiation therapy （CRT）. In the present study, we examined the effects of the traditional Chinese medicine Shenqi Fuzheng Injection （SFI） on RIBI in mice, and explored the underlying mechanisms. Methods： C57BL/6J mice were subjected to a single dose of 20-Gy CRT. The mice were treated with SFI （20 mL·kg^-1-d^-1, ip） for 4 weeks. Morris water maze test was used to assess the cognitive changes. Evans blue leakage and a horseradish peroxidase （HRP） assay were used to evaluate the integrity of the blood-brain barrier （BBB）. The expression of inflammatory factors and microglial activation in brain tissues were detected using RT-PCR, Western blotting and immunofluorescence staining. Results： CRT caused marked reductions in the body weight and life span of the mice, and significantly impaired their spatial learning. Furthermore, CRT significantly increased the BBB permeability, number of activated microglia, expression levels of TNF-α and IL-1β, and the levels of phosphorylated p65 and PIDD-CC （the twice-cleaved fragment of p53-induced protein with a death domain） in the brain tissues. Four-week SFI treatment （administered for 2 weeks before and 2 weeks after CRT） not only significantly improved the physical status, survival, and spatial learning in CRT-treated mice, but also attenuated all the CRT-induced changes in the brain tissues. Four-week SFI pretreatment （administered for 4 weeks before CRT） was less effective. Conclusion： Administration of SFI effectively attenuates irradiation-induced brain injury via inhibition of the NF-κB signaling pathway and microglial activation.Aim： Radiation-induced brain injury （RIBI） is the most common and severe adverse effect induced by cranial radiation therapy （CRT）. In the present study, we examined the effects of the traditional Chinese medicine Shenqi Fuzheng Injection （SFI） on RIBI in mice, and explored the underlying mechanisms. Methods： C57BL/6J mice were subjected to a single dose of 20-Gy CRT. The mice were treated with SFI （20 mL·kg^-1-d^-1, ip） for 4 weeks. Morris water maze test was used to assess the cognitive changes. Evans blue leakage and a horseradish peroxidase （HRP） assay were used to evaluate the integrity of the blood-brain barrier （BBB）. The expression of inflammatory factors and microglial activation in brain tissues were detected using RT-PCR, Western blotting and immunofluorescence staining. Results： CRT caused marked reductions in the body weight and life span of the mice, and significantly impaired their spatial learning. Furthermore, CRT significantly increased the BBB permeability, number of activated microglia, expression levels of TNF-α and IL-1β, and the levels of phosphorylated p65 and PIDD-CC （the twice-cleaved fragment of p53-induced protein with a death domain） in the brain tissues. Four-week SFI treatment （administered for 2 weeks before and 2 weeks after CRT） not only significantly improved the physical status, survival, and spatial learning in CRT-treated mice, but also attenuated all the CRT-induced changes in the brain tissues. Four-week SFI pretreatment （administered for 4 weeks before CRT） was less effective. Conclusion： Administration of SFI effectively attenuates irradiation-induced brain injury via inhibition of the NF-κB signaling pathway and microglial activation.

关 键 词：Shenqi Fuzheng Injection traditional Chinese medicine cranial radiation therapy radiation-induced brain injury blood-brain barrier MICROGLIA NF-κB 

分 类 号：Q26[生物学—细胞生物学] Q274