藁本内酯对脑缺血再灌注大鼠中性粒细胞胞外诱捕网的影响OA

Objective:To explore the possible mechanisms by which ligustilide(LIG)exerts neuroprotective effects on ischemic stroke(IS)by inhibiting the release of neutrophil extracellular traps(NETs),promoting blood-brain barrier repair,and alleviating post-ischemic neuroinflammation,thereby providing a new direction for IS treatment.Methods:A middle cerebral artery occlusion(MCAO)model was established in rats.The rats were divided into the sham operation(Sham)group,model(Model)group,low-and high-dose LIG groups(20,40 mg·kg-1),and the NET inhibitor CI-amidine group(CI-amidine,10 mg·kg-1).Drug treatments were administered for 3 days.Neurological injury after ischemia was evaluated by 2,3,5-triphenyltetrazolium chloride(TTC)staining,neurological deficit scoring,and brain index measurement.Flow cytometry and Western blot were used to analyze changes in neutrophil expression.Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3(H3Cit).Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors,including interleukin-18(IL-18)and interleukin-1β(IL-1β).Results:Compared with the Sham group,the Model group exhibited significant brain tissue injury(P＜0.05),significantly increased neutrophil numbers and NET expression(P＜0.05),significantly impaired blood-brain barrier permeability(P＜0.05),and significantly increased expression of inflammatory factors(P＜0.05).Compared with the Model group,both low-and high-dose LIG significantly alleviated brain tissue injury in rats(P＜0.01),inhibited neutrophil numbers and NET expression(P＜0.01),reduced blood-brain barrier damage(P＜0.01),and suppressed the expression of inflammatory factors IL-18 and IL-1β(P＜0.01),thereby ultimately exerting a neuroprotective effect.Conclusion:The neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.