外侧苍白球注射铁死亡诱导剂对小鼠运动行为的影响

Effect of stereotactic injection of a ferroptosis inducer in the external segment of globus pallidus on motor behavior in mice

目的 探讨外侧苍白球(GPe)立体定位注射铁死亡诱导剂RSL3或Erastin对小鼠运动行为的影响。方法 将8周龄雄性C57BL/6小鼠随机分为对照组8只、实验组24只(Erastin组12只、RSL3组12只)。借助脑立体定位注射技术,实验组小鼠GPe双侧注射200 nL的RSL3或Erastin(浓度为10μmol/L),对照组小鼠注射等体积生理盐水。两周后,采用步态分析实验检测小鼠的运动能力,采用免疫印迹法检测小鼠GPe中长链酯酰辅酶A合成酶4(ACSL4)和谷胱甘肽过氧化物酶4(GPX4)的表达。结果 与对照组相比,Erastin组和RSL3组小鼠的摆动速度均升高,RSL3组小鼠的最大接触面积、脚印面积和步幅长度均发生明显改变,差异均有显著性(F=5.433~7.486,q=4.039~5.446,P<0.05)。Erastin组和RSL3组小鼠GPe中GPX4表达水平均明显下降,而RSL3组小鼠GPe中ACSL4表达水平明显升高,差异均有统计学意义(F=6.207、19.740,q=3.847~7.735,P<0.01)。结论 小鼠GPe立体定位注射铁死亡诱导剂RSL3或Erastin两周后可发生铁死亡,运动行为增强。

Objective To investigate the effect of stereotactic injection of the ferroptosis inducer RSL3 or Erastin in the external segment of the globus pallidus(GPe)on the motor behavior of mice.Methods Male C57BL/6 mice,aged 8 weeks,were randomly divided into control group with 8 mice and experimental group with 24 mice(12 mice in Erastin group and 12 mice in RSL3 group).By means of the stereotactic injection technique,the mice in the experimental group were injected with 200 nL RSL3 or Erastin(with a concentration of 10μmol/L)into the bilateral GPe,and thosein the control group were injected with an equal volume of normal saline.After two weeks,gait analysis was used to observethe motor behavior of mice,and Western blot was used to measure the protein expression levels of long-chain acyl-CoA synthetase 4(ACSL4)and glutathione peroxidase 4(GPX4)in mouse GPe.Results Compared with the control group,the Erastin group and the RSL3 group had a significant increase in the swing speed of mice,and the RSL3 group had significant changes in maximum contact area,footprint area,and stride length(F=5.433-7.486,q=4.039-5.446,P<0.05).Compared with the control group,the Erastin group and the RSL3 group had a significant reduction in the protein expression level of GPX4 in the GPe of mice,and the RSL3 group had a significant increase in the protein expression level of ACSL4(F=6.207,19.740;q=3.847-7.735;P<0.01).Conclusion Stereotactic injection of the ferroptosis inducer RSL3 or Erastin in the GPe of mice can induce ferroptosis after two weeks,with enhanced motor behavior of mice.