Cao Jing-Jing, Pan Ji-Rong, Zhang Dong-Yuan, Chen Bo-Rui, Zhang Ling, Meng Ai-Min, Qin Chuan
Institute of Laboratory Animal Science,Comparative Medical Center,NHC Key Laboratory of Human Disease Comparative Medicine,Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,CAMS and PUMC,Beijing 100021,China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2022 Jun;44(3):357-365. doi: 10.3881/j.issn.1000-503X.14483.
Objective To explore the effects of interleukin-6 (IL-6) gene knockout on the cognitive function and pathological changes in 5×FAD transgenic mice of Alzheimer's disease.Methods IL-6 mice were crossed with 5×FAD mice to establish the 5×FAD;IL-6 mouse model,and 3-month-old and 10-month-old mice were selected for experiments.The cognitive function of mice was detected by behavioral tests,and HE staining and β-amyloid (Aβ) immunohistochemical staining were performed to detect the pathological changes of mouse brain tissue.Results The number of 5×FAD;IL-6 model mice (3 months old,=20;10 months old,=5) and 5×FAD littermate control (3 months old,=26;10 months old,=24) conformed to the Mendel's law.Compared with that of the 5×FAD mice at the same age,the discrimination ratio of 3-month-old 5×FAD;IL-6 mice increased in the novel object recognition test (=3.890,=0.002).Morris water maze test results showed that the 3-month-old 5×FAD;IL-6 mice had longer time spent in target quadrant (=3.797,=0.012) and more times of crossing platform (=2.505,=0.017) than the 5×FAD mice at the same age.The results of immunohistochemical staining showed that IL-6 knockout reduced the Aβ deposition in the hippocampus (=13.490,=0.002;=45.680,<0.001) and cortex (=16.830,=0.001;=14.180,=0.001) of 5×FAD mice.Conclusion IL-6 gene knockout can significantly improve the spatial memory and reduce the Aβ deposition in the brain of 5×FAD mice.
目的 探讨白细胞介素-6（IL-6）基因敲除对阿尔茨海默病5×FAD转基因小鼠认知功能及病理变化的影响。方法 将IL-6基因敲除小鼠与5×FAD小鼠杂交，建立5×FAD;IL-6小鼠模型，选取3月龄和10月龄小鼠进行实验。通过行为学测试检测小鼠的认知功能，采用苏木精-伊红（HE）染色和β-淀粉样蛋白（Aβ）免疫组化染色检测小鼠脑组织的病理变化。结果 5×FAD;IL-6模型小鼠（3月龄，n = 20；10月龄，n = 5）和5×FAD同窝对照小鼠（3月龄，n = 26；10月龄，n = 24）数量符合孟德尔定律。在新物体识别试验中，与同年龄的5×FAD小鼠相比，3月龄5×FAD;IL-6小鼠的辨别率升高（t = 3.890，P = 0.002）。莫里斯水迷宫试验结果显示，3月龄5×FAD;IL-6小鼠在目标象限的停留时间长于同年龄的5×FAD小鼠（t = 3.797，P = 0.012），穿越平台的次数多于同年龄的5×FAD小鼠（t = 2.505，P = 0.017）。免疫组化染色结果显示，IL-6基因敲除减少了5×FAD小鼠海马体（t = 13.490，P = 0.002；t = 45.680，P < 0.001）和皮质（t = 16.830，P = 0.001；t = 14.180，P = 0.001）中的Aβ沉积。结论 IL-6基因敲除可显著改善5×FAD小鼠的空间记忆，并减少其脑内Aβ沉积。
