Electroacupuncture alleviates neuroinflammation by regulating microglia polarization via STAT6/PPARγ in ischemic stroke rats
Description
Our previous study showed that electroacupuncture (EA) intervention produced a protective effect on cerebral ischemia-reperfusion injury (CIRI) in rats and may be related to the anti-inflammatory effects of microglia. This study aimed to investigate further whether EA could modulate neuroinflammation by targeting the STAT6/PPARγ pathway, a key regulator of microglia. Middle cerebral artery occlusion (MCAO) model rats were used, and 6 h after reperfusion, EA interventions were performed in Chize (LU 5), Hegu (LI 4), Sanyinjiao (SP 6), and Zusanli (ST 36) on the affected side of the rats, the group that received EA in combination with the STAT6 phosphorylation inhibitor AS1517499 was used as a parallel control. The degree of neurological impairment, infarct volume, microglia polarization, inflammation levels and activity changes in STAT6/PPARγ pathway were then assessed by neurological deficit score, TTC staining, immunofluorescence, western blotting, and quantitative real-time PCR. The data showed that EA intervention significantly alleviated nerve injury, reduced infarct volume, enhanced STAT6/PPARγ pathway activity, inhibited NF-κB activity, increased the number of M2 microglia and the release of associated anti-inflammatory factors, and inhibited microglia M1-type polarization and expression of pro-inflammatory factors. In contrast, inhibition of STAT6 phosphorylation exacerbated neural damage, inhibited STAT6/PPARγ pathway activity, promoted microglia M1-type polarization and exacerbated neuroinflammation, resulting in an attenuated positive effect of EA intervention on the regulation of microglia-associated neuroinflammation in MCAO rats. Therefore, we concluded that EA intervention could attenuate microglia-associated neuroinflammation by enhancing the activity of STAT6/PPARγ pathway, thereby reducing CIRI in MCAO rats.
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Steps to reproduce
WB, ELISA and qPCR assays were performed according to the conventional methods in the literature.