Chk2敲除可通过增强抗氧化能力改善由Bmi-1缺失所致的小鼠脑衰老表型

Chk2 knockout attenuates the brain aging phenotype of Bmi-1 deficiency mice by enhancing the antioxidant capacity

目的:探索细胞周期检测点激酶2(cell-cycle checkpoint kinase 2,Chk2)敲除是否能改善由B淋巴瘤Mo-MLV插入区1(B cell-specific MLV integration site-1,Bmi-1)缺失所致的小鼠脑衰老表型。方法:取2月龄Bmi-1基因敲除(Bmi-1^(-/-))小鼠、Chk2基因敲除(Chk2^(-/-))小鼠、Bmi-1和Chk2双敲(Bmi-1^(-/-)Chk2^(-/-))小鼠以及同窝野生型(wild type,WT)小鼠脑组织,通过免疫组织化学染色检测不同组小鼠脑组织皮层、海马、下丘脑中NeuN、GFAP、Iba1、p16等指标的变化,通过Western blot检测不同组小鼠脑皮质中p16、SOD1、SOD2蛋白表达量的差异。结果:与同窝WT小鼠相比,Bmi-1^(-/-)小鼠在上述脑区中NeuN、Iba1阳性细胞百分率明显减少,GFAP与p16的阳性细胞百分率明显增加,SOD1、SOD2蛋白表达量明显降低,p16蛋白表达量明显上升,而在Chk2^(-/-)小鼠中NeuN、Iba1阳性细胞百分率则增加,GFAP与p16的阳性细胞百分率明显减少,SOD1、SOD2蛋白表达量明显上调,p16蛋白表达量明显下降;与Bmi-1^(-/-)小鼠相比,Bmi-1^(-/-)Chk2^(-/-)小鼠在上述脑区中NeuN、Iba1阳性细胞百分率明显增加,GFAP与p16的阳性细胞百分率明显减少,SOD1和SOD2蛋白表达量明显上升,p16蛋白表达量明显下降。结论:Chk2敲除可通过增强抗氧化能力,从而改善由Bmi-1缺失所致的小鼠脑衰老表型。

Objective:To explore whether the cell cycle checkpoint kinase 2(cell-cycle checkpoint kinase 2,Chk2)knockout could alleviate the brain aging phenotype of B cell-specific MLV integration site-1(B cell-specific MLV integration site-1,Bmi-1)deficiency mice. Methods:The two-month-old of Bmi-1 gene knockout(Bmi-1^(-/-))mice,Chk2 gene knockout(Chk2^(-/-))mice,Bmi-1 and Chk2 double knockout(Bmi-1^(-/-) Chk2^(-/-))mice and wild type(wild type,WT)littermates were used in this study. The expression of NeuN,GFAP,Iba1 and p16 in the cerebral cortex,hippocampus and hypothalamus of the above four groups of mice were detected by immunohistochemical staining. The expression of p16,SOD1 and SOD2 protein in the cerebral cortex of the above four groups were analyzed by Western blot. Results:Compared with the WT littermates,the percentages of NeuN and Iba1 positive cells in the above brain regions were significantly decreased,the percentage of GFAP and p16 positive cells were significantly increased,the protein expression levels of SOD1 and SOD2 were significantly decreased,and the protein expression levels of p16 were significantly increased in the Bmi-1^(-/-) mice. However,in Chk2^(-/-) mice,the percentages of NeuN and Iba1 positive cells were increased,the percentage of GFAP and p16 positive cells were significantly decreased,the protein expressions of SOD1 and SOD2 were significantly increased,and the protein expression of p16 were significantly decreased. Compared with the Bmi-1^(-/-) mice,Chk2 knockout increased the percentage of NeuN and Iba1 positive cells in the above brain regions,decreased the percentage of GFAP and p16 positive cells,increased the protein expressions of SOD1 and SOD2,and decreased the protein expressions of p16 in the Bmi-1^(-/-) Chk2^(-/-) mice significantly.Conclusion:Chk2 knockout can attenuate the brain aging phenotype induced by Bmi-1 deficiency in mice by enhancing the antioxidant capacity.