摘要
Background Baicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke. Most of the studies of Toll-like receptor 2/4 （TLR2/4） during cerebral ischemia had defined their specific expressions in microglia in hippocampus tissue. To explore the targets of baicalin in stroke, we detected the expressions of TLR2/4 in vitro/vivo.Methods By constructing a cerebral ischemia-reperfusion model in vivo and glucose oxygen deprivation model, we successfully induced neuron damage, then added baicalin and detected expressions of TLR2/4, nuclear factor-kB （NF-kB）, tumor necrosis factor-alpha （TNFα）, and interleukin-1β （IL-1β） in mRNA level and protein level.Results We found distinct upregulations of TLR2/4 and TNFα in both mRNA level and protein level in PC12 cells and primary neurons. Moreover, TLR2/4 and TNFα expressions were significantly higher in mice hippocampus treated with cerebral ischemia-reperfusion. Baicalin could downregulate the expressions of TLR2/4 and TNFα in the damaged cells and mice hippocampus effectively.Conclusions Neurons could respond to the damage and activate the related signal pathway directly. TLR2/4 responsed to the damage and sent the signal to downstream factor TNFα through activating NF-kB. Baicalin could inhibit the inflammatory reaction in neuron damage and TLR might be its targets, which explained why baicalin could widely be used in the clinical treatment of stroke.
Background Baicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke. Most of the studies of Toll-like receptor 2/4 （TLR2/4） during cerebral ischemia had defined their specific expressions in microglia in hippocampus tissue. To explore the targets of baicalin in stroke, we detected the expressions of TLR2/4 in vitro/vivo.Methods By constructing a cerebral ischemia-reperfusion model in vivo and glucose oxygen deprivation model, we successfully induced neuron damage, then added baicalin and detected expressions of TLR2/4, nuclear factor-kB （NF-kB）, tumor necrosis factor-alpha （TNFα）, and interleukin-1β （IL-1β） in mRNA level and protein level.Results We found distinct upregulations of TLR2/4 and TNFα in both mRNA level and protein level in PC12 cells and primary neurons. Moreover, TLR2/4 and TNFα expressions were significantly higher in mice hippocampus treated with cerebral ischemia-reperfusion. Baicalin could downregulate the expressions of TLR2/4 and TNFα in the damaged cells and mice hippocampus effectively.Conclusions Neurons could respond to the damage and activate the related signal pathway directly. TLR2/4 responsed to the damage and sent the signal to downstream factor TNFα through activating NF-kB. Baicalin could inhibit the inflammatory reaction in neuron damage and TLR might be its targets, which explained why baicalin could widely be used in the clinical treatment of stroke.
基金
This work was supported by grants from the National Natural Science Foundation of China （No. 30973896, No. 30801523, and No. 81073092） and the National S＆T Major Special Project for New Drug R＆D Program of China （No. 2009ZX09103-301, No. 2009ZX09502, No. 2009ZX09308-003, and No. 2011ZX09101- 002-11）.Acknowledgments： We thank specially all our colleagues in our laboratory.
