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Aim Brain inflammation plays an important role in the pathophysiology of many psychiatric and neurological diseases.Angiotensin Ⅱ type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 microglia activation.The ARB telmisartan suppresses neuroinflammation in cultured neuronal cells.We wished to clarify whether telmisartan prevents microgliamediated neuroinflammation through microglia polarization to an antiinflammatory M2 phenotype.Methods The gene expression of M1 markers and M2 markers was measured by RTPCR.The AMPK phosphorylation level and M2 marker CD206 protein expression were determined by Western blot.TNFt and IL10 release was measured by ELISA.The gene knowdown was performed by the siRNA transfection experiment.Results Our results demonstrated that telmisartan promoted M2 polarization in LPSstimulated BV2 and primary microglia cells.The promoting effects of telmisartan on M2 polarization were attenuated by an AMPactivated protein kinase (AMPK) inhibitor or AMPK knockdown, indicating that AMPK activation participates on telmisartan effects.Furthermore, telmisartan enhanced brain AMPK activation and M2 gene expression in a mouse model of LPSinduced neuroinflammation.Conclusion Our results indicate that telmisartan can be considered as a novel AMPK activator, suppressing neuroinflammation by promoting microglia M2 polarization.Telmisartan may provide a novel and safe therapeutic approach for the treatment of brain disorders associated with neuroinflammation.