三七总皂苷抑制铁死亡和炎症反应减轻大鼠脑缺血再灌注损伤

Panax notoginseng saponins attenuate cerebral ischemia reperfusion injury in rats by inhibiting ferroptosis and inflammation

目的:基于三七总皂苷(PNS)对铁死亡和炎症反应的调控作用,探讨PNS抗脑缺血再灌注损伤(CIRI)机制。方法:采用大脑中动脉阻塞/复灌注(MCAO/R)方法建立大鼠CIRI模型,PNS干预后,各组大鼠进行Longa评分比较;观察脑梗死体积;试剂盒检测缺血侧大脑皮质组织中Fe2+、GSH、MDA、IL-1β、TNF-α和IL-6含量;Western blot检测脑组织中铁死亡关键调控蛋白谷胱甘肽过氧化物酶4(GPX4)的表达水平。结果:MCAO/R后,大鼠神经评分显著增加,有明显脑梗死区,皮层组织中Fe2+和MDA及IL-1β、TNF-α、IL-6含量显著增加,而GSH含量和GPX4水平显著降低。与MCAO/R组相比,PNS干预组大鼠神经功能评分显著降低、脑梗死体积减小、脑组织中Fe2+和MDA及IL-1β、TNF-α、IL-6含量显著降低,而GSH含量和GPX4水平显著增加。结论:PNS可有效减轻CIRI,其机制与抑制铁死亡和炎症反应有关。

Objective:To explore the mechanism of Panax notoginseng saponins(PNS)against cerebral ischemia-reperfusion injury(CIRI)based on regulatory effects of PNS on ferroptosis and inflammation.Methods:CIRI model was induced by middle cere⁃bral artery occlusion-reperfusion(MCAO/R)in rats.After PNS intervention,Longa scores were applied to assess neurological changes.Volume of cerebral infarction was observed and contents of Fe 2+,GSH,MDA,IL-1β,TNF-αand IL-6 in cerebral cortex of rats were determined by the kits.Besides,level of GPX 4 was detected by Western blot.Results:After MCAO/R of rats,the infarct volume and neurological deficit score of rats were strongly increased.Fe 2+and MDA content in brain tissue,and IL-1β,TNF-αand IL-6 also increased.Conversely,there were significant decrease in content of GSH and level of GPX 4.PNS intervention group saw substantially lower neurological deficit scores and cerebral infarct volume than MCAO/R group.Moreover,content of Fe 2+and MDA in brain tissue,as well as IL-1β,TNF-αand IL-6 all fell,while there were significant increase in GSH content and GPX 4 levels.Conclusion:PNS can effectively reduce CIRI,and its neuroprotective mechanism may be related to the inhibition of ferroptosis and inflammation.