免疫相关GTP酶Irgm1对小鼠暂时性大脑中动脉缺血再灌注模型脑神经元自噬发生的影响

The effect of immunity-related GTPase 1 （ Irgml ） on neuronal autophagy regulation of tMCAO mice

目的探讨免疫相关GTP酶1（Irgml）在小鼠暂时性大脑中动脉缺血再灌注模型（tMCAO）中的表达及其对tMCAO小鼠大脑神经元内自噬发生的影响。方法采用westernblotting和免疫荧光染色，检测Irgml和自噬相关基因LC3I／II及P62在Irgml^＋/＋小鼠tMCAO脑组织内的表达水平及细胞定位；进一步比较Irgml^＋/＋及Irgml。小鼠tMCAO大脑神经元内自噬发生的差异。结果相比于假手术（sham）组，Irgml在Irgml^＋/＋小鼠tMCAO脑组织中表达明显增高，且主要分布于损伤侧皮层神经元内；同时我们也证实在小鼠tMCAO脑组织中LC3-II表达增加（t=-16．448，P〈0．01），而P62表达明显减低（t=3．975，P〈0．05）。我们进一步实验发现Irgml。小鼠tMCAO脑组织内LC3-II表达量低于Irgml^＋/＋小鼠tMCAO（t=4．073，P〈0．05），而P62表达量高于Irgml^＋/＋小鼠tMCAO（t=-3．383，P〈0．05）。结论在小鼠tMCAO模型中，Irgml参与调节大脑神经元的自噬活动。

Objective To investigate the impact of immunity-related GTPase Irgml on the regulation of neuronal autophagy in tMCAO mice. Methods Brain tissues were collected from lrgml ＋/＋ tMCAO mice. Ir- gml and autophagy-related genes LC3- I / 11 and p62 expression were detected by western blotting and immu- nofluorescence staining. In addition, we compared the expression of autophagy related genes between the brain tissues of Irgm ＋/＋ and Irgml -/- mice after tMCAO. Results Irgml was increased in the cortex neurons of Ir- gml ＋/＋ mice tMCAO compared to sham group. The increatted Irgml was accompanied by enhanced neuronal autophagic activity proved by higher expression of LC3-II （ t = -16. 448, P 〈 0.01 ） and lower expression of p62 （t = 3. 975 ,P 〈 0.05） in Irgml ＋/＋ mice tMCAO. However, we found that in Irgml -/- mice the exprossion of Lc3- II was lower （ P 〈 O. 01 ） while the expression of p62 was higher （ P 〈 0. 05 ） compared with that in Ir- gml ＋/＋ mice. Conclusion The increased expression of Irgml in the neurons during tMCAO is important for neuronal autophagy.