The mechanism by which epidermal growth factor 8 regulates microglia polarization in transient cerebral ischemia
10.3760/cma.j.issn.0254-1424.2021.07.003
- VernacularTitle:乳脂球-表皮生长因子8对脑缺血后小胶质细胞极化的调控作用机制研究
- Author:
Yingying FANG
1
;
Jinghui ZHANG
Author Information
1. 南方医科大学基础医学院，广州 510515
- Keywords:
Cerebral artery occlusion;
Microglia polarization;
Epidermal growth factor 8;
Signal transduction and transcription factor 3
- From:
Chinese Journal of Physical Medicine and Rehabilitation
2021;43(7):588-594
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the function of epidermal growth factor 8 in the polarization of microglia after ischemic brain injury and its mechanism.Methods:Forty C57BL/6 mice were randomly divided into a sham operation group, an ischemia group, a recombinant mouse milk fat globule epidermal growth factor 8 (rmMFG-E8) group and an rmMFG-E8 + colivelin TFA group, each of 10. The middle cerebral artery occlusion and reperfusion model (tMCAO) was established in all except the sham operation group. Right after the modelling the mice in the rmMFG-E8 group were immediately injected with 2μL of 0.4μg/μL of rmMFG-E8 into the ventricle contralateral to the cerebral infarction. The rmMFG-E8+ Colivelin TFA group was injected with the same dose of rmMFG-E8 plus 2μL of 5pmol/μL colivelin TFA. On the 1st, 3rd, 5th and 7th day after the modelling, neurological functioning was documented using behavioral tests. The volume proportion of the cerebral infarction was observed after tissue staining on the 7th day after the operation. The gene expression levels of M1 polarization marker-induced nitric oxide synthase (iNOS), M2 polarization marker arginase-1 (Arg1) and mouse chitinase-like molecule 3 (YM1) in the microglia were detected using real-time fluorescence quantitative polymerase chain reactions. The protein expression levels of MFG-E8, phosphorylated signal transduction and transcription factor 3 (p-STAT3) and cytokine signal transduction inhibitor-3 (SOCS3) were determined using western blotting.Results:The behavior tests revealed significant differences between the sham operation group and the other groups on all four days. Compared with the sham operation group, the average expression of MFG-E8 gene and its protein, Arg1 and Ym1, and the SOCS3/GAPDH protein ratio had decreased significantly in the ischemic group, while the average expression of iNOS and the p-STAT3/STAT3 protein ratio had increased significantly. On the 7th day after the modelling, compared with the ischemic group, the infarct volume was significantly smaller in the rmMFG-E8 group. The average expression of iNOS and the average p-STAT3/STAT3 ratio in the rmMFG-E8+ colivelin TFA group had increased significantly compared with the rmMFG-E8 group, while the average expression of Arg1 and Ym1, and the SOCS3/GAPDH ratio were significantly lower.Conclusion:MFG-E8 promotes the polarization of M2-type microglia after cerebral ischemia through STAT3 signaling, promoting the recovery of neurological functioning.
