活性氧簇介导的氧化应激及细胞焦亡在大鼠脑缺血再灌注损伤中的作用

Role of Reactive Oxygen Species Mediated Oxidative Stress and Pyroptosisin Cerebral Ischemia-reperfusion Injury in Rats

目的研究活性氧簇(ROS)介导的氧化应激及细胞焦亡在大鼠脑缺血再灌注(I/R)损伤中的作用。方法成年雄性SD大鼠分为假手术(Sham)组、I/R组、ROS清除剂N乙酰半胱氨酸-低剂量(NAC-L)组、NAC中等剂量(NAC-M)组、NAC高剂量(NAC-H)组,建立脑I/R损伤模型并给予50、100、200 mg/kg NAC腹腔注射干预。再灌注后24 h,评价神经功能,检测脑梗死面积百分比、ROS、丙二醛(MDA)、4-羟基壬烯醛(4-HNE)、总抗氧化力(T-AOC)、裂解型caspase-1(Cleaved caspase-1)、gasdermin D的N端片段(GSDMD-N)。结果I/R组脑梗死面积百分比、ROS、MDA、4-HNE含量、Cleaved caspase-1、GSDMD-N表达水平均明显增加,T-AOC含量明显降低(P<0.05);NAC-L组、NAC-M组、NAC-H组脑梗死面积百分比、ROS、MDA、4-HNE含量、Cleaved caspase-1、GSDMD-N表达水平均明显降低,T-AOC含量明显增加(P<0.05)且NAC剂量越高,上述变化越显著。结论ROS介导的氧化应激及细胞焦亡参与大鼠脑I/R损伤。

Objective To study the role of reactive oxygen species(ROS)-mediated oxidative stress and pyroptosis in the cerebral ischemia-reperfusion(I/R)injury in rats.Methods Adult male SD rats were divided into 5 groups as follows:the sham group,the I/R group,the ROS scavenger N-acetylcysteine low dose(NAC-L)group,the NAC medium dose(NAC-M)group and the NAC high dose(NAC-H)group.The cerebral I/R injury model was established and 50,100 and 200 mg/kg NAC were injected intraperitoneally before ischemia and reperfusion as an intervention.The neurological function was evaluated 24 h after reperfusion,the percentage of cerebral infarction area,and the levels of ROS,malondialdehyde(MDA),4-hydroxynonenal(4-HNE)and total antioxidant capacity(T-AOC)were measured.The expression levels of cleaved caspase-1 and N-terminal of gasdermin D(GSDMD-N)were detected.Results In the I/R group,the percentage of cerebral infarction area,the amount of ROS,MDA,4-HNE,and the expression levels of cleaved caspase-1 and GSDMD-N were significantly increased,while the amount of T-AOC was significantly decreased(P<0.05).In the NAC-L,NAC-M and NAC-H groups,the percentage of cerebral infarction area,the amount of ROS,MDA,4-HNE,and the expression levels of cleaved caspase-1 and GSDMD-N were significantly decreased,while the amount of T-AOC was significantly increased(P<0.05).The changes of the above indexes became more obvious with the increase of the NAC dose.Conclusion ROS mediated oxidative stress and pyroptosis are involved in the cerebral I/R injury in rats.