Page 33 - 南京医科大学学报自然科学版

第41卷第7期 南京医科大学学报（自然科学版）
2021年7月 Journal of Nanjing Medical University（Natural Sciences） ·963 ·

·基础医学·

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

崔 敏 ，刘轶宁 ，庄旻羽 ，吕佳璐 ，金瑶瑶 ，张永杰 1，2*
1，2
1，2
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1 南京医科大学人体解剖学系，衰老及相关疾病研究重点实验室，第一临床医学院，江苏 南京 211166
［摘 要］ 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
-/-
-/-
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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，
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-/-
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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。
［关键词］ 脑；衰老；Bmi⁃1；Chk2；抗氧化
［中图分类号］ R339.34 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）07⁃963⁃07
doi：10.7655/NYDXBNS20210705

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

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CUI Min ，LIU Yining ，ZHUANG Minyu ，LÜ Jialu ，JIN Yaoyao ，ZHANG Yongjie 1，2*
1 2 3
Department of Human Anatomy，Key Laboratory for Aging & Diseases，First Clinical Medical College，Nanjing
Medical University，Nanjing 211166，China
［Abstract］ 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
-/-
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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，
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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

［基金项目］ 国家自然科学基金（81472081，81100942）；江苏省自然科学基金（BK2010539）；江苏省青蓝工程
∗
通信作者（Corresponding author），E⁃mail：zhangyongjie@njmu.edu.cn