Study on Anti-inflammatory Activity and Mechanism of Ticagrelor in vitro
The test aims to investigate the effects of ticagrelor on the anti-inflammatory activity of NLRP3 inflammasome constructed by human umbilical vein endothelial cells(HUVECs)and mouse bone marrow-derived macrophages(BMDMs).The inflammation model of HUVECs in vitro was induced by LPS,the effects of ticagrelor on the expression of TNF-α,IL-1β,IL-6 and Il-10 were detected by ELISA;NLRP3 inflammasome of BMDMs was induced by LPS+nigericin,and the activation of the inflammasome was detected by ELISA and Western Blot.Before and after induction of BMDMs NLRP3 inflammasome,different concentrations of ticagrelor were given respectively,the expression of IL-1 β,TNF-α and Caspase-1 were detected by ELISA and Western blot.The sepsis model was induced by LPS and treated with ticagrelor,the expression of IL-1 β,IL-6 and TNF-α were detected by ELISA.Result showed:1.The inflammation model of HUVECs induced by LPS was concentration-dependent,and the cell activity decreased gradually with the increase of concentration;the induction efficiency was the highest at the intermediate concentration of 100 ng/mL and 200 ng/mL,and the cell activity increased slightly or remained unchanged with the induction time.2.In the LPS-induced HUVECs inflammatory cell model,different concentrations of ticagrelor can down-regulate the levels of TNF-α,IL-6 and IL-1 β inflammatory factors,and up-regulate the levels of IL-10 inflammatory factors,and the changes of inflammatory factors were dose-dependent.3.The expression of Caspase-1 and IL-1β could be inhibited by drug intervention before and after the activation of inflammasome,and the degree of inhibition was dose-dependent;however,the expression of TNF-α decreased during pre-activation drug intervention,but remained unchanged after activation drug intervention.4.The expressions of inflammatory factors IL-1β,IL-6 and TNF-α were signi-ficantly decreased in the LPS-induced sepsis group.Ticagrelor has obvious anti-inflammatory activity in HUVECs cell assay in vitro.By constructing mouse BMDMs inflammasome,the regulation of inflammation on immune cells was studied,and it was found that ticagrelor can act on the activation of NLRP3 inflammasome,inhibit the activation of NF-κB signaling pathway,and avoid the conti-nuation of inflammatory response.
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