炎症因子IL-4可能通过自噬导致正常鼠认知功能下降

Inflammatory cytokine interleukin-4 may induce cognitive function impairment via autophagy in normal mice

目的:研究腹腔注射白细胞介素-4(interleukin-4,IL-4)对C57BL/6小鼠学习记忆能力的影响。方法:将10只C57BL/6小鼠随机分成2组:IL-4干预组和对照组。在注射IL-4 1 d后进行水迷宫实验,包括5天定位航行和1天空间探索实验。采用Western blot和RT-PCR对自噬标记物微管相关蛋白1轻链3(microtubule associated protein 1 light chain 3,MAP1LC3,LC3)进行检测。结果:IL-4注射组小鼠学习记忆能力较对照组明显下降(穿越平台次数:4.750±0.500 vs.6.500±0.577;t=4.583,P=0.004)。免疫印迹显示,IL-4干预组小鼠脑组织中LC3较对照组明显增多(皮质:0.760±0.091 vs.0.482±0.085;t=-6.702,P=0.000;海马:0.772±0.068 vs.0.486±0.047;t=-10.267,P=0.000)。RT-PCR同样验证了这个趋势(皮质:1.422±0.002 vs.1.000±0.000;t=-311.903,P=0.000;海马:1.434±0.005 vs.1.000±0.000;t=-162.197,P=0.000)。结论:IL-4可能通过大量增加小鼠自噬作用,降低小鼠的学习记忆能力。

Objective：to explore the effect of interleukin-4（IL-4）on the cognitive function in C57BL/6 mice. Methods：Ten C57BL/6mice were randomly divided into two groups：IL-4 intervention group（the mice intraperitoneally injected with IL-4 at the concentration of 100 ng/kg）and the control group. Morris water maze including five days of place navigation and one day of spatial probe was performed on the next day after intraperitoneal injection of IL-4. Microtubule associated protein 1 light chain 3（MAP1LC3,LC3）was detected by Western blot and reverse transcription-polymerase chain reaction（RT-PCR）. Results：Compared with those of control group,the level of learning and memory of the mice in IL-4 intervention group was significantly decreased（times of crossing platform：4.750±0.500 vs. 6.500±0.577;t=4.583,P=0.004）. Western blot showed that the expression of LC3 was increased in the mice in IL-4 intervention group than in control group（cortex：0.760±0.091 vs. 0.482±0.085;t=-6.702,P=0.000;hippocampus：0.772±0.068 vs.0.486±0.047;t=-10.267,P=0.000）. RT-PCR also verified this trend（cortex：1.422±0.002 vs. 1.000±0.000;t=-311.903,P=0.000;hippocampus：1.434 ± 0.005 vs. 1.000±0.000;t=-162.197,P=0.000）. Conclusion：IL-4 affects the function of autophagy,and the excessive autophagy may cause the damage to cognitive function in the mice.