目的 探讨脑心通胶囊通过抑制铁死亡减少大鼠脑缺血再灌注损伤。方法 雄性SD大鼠随机分为假手术组、模型组、脑心通（110.0 mg/kg）组、金纳多（21.6 mg/kg）组、p53抑制剂（25.0 mg/kg）组和p53抑制剂（25.0 mg/kg）＋脑心通（110.0 mg/kg）组。通过短暂性大脑中动脉闭塞制备脑缺血再灌注损伤大鼠模型，术后24 h进行指标评定及取材，评估各组大鼠神经功能评分检测神经功能；2,3,5-三苯基氯化四氮唑（2,3,5-triphenyltetrazolium chloride solution，TTC）法检测脑梗死面积；苏木素-伊红（hematoxylin-eosin，HE）染色观察海马形态结构；透射电镜观察超微结构；生化试剂检测海马组织亚铁、脂质过氧化物含量；逆转录实时定量聚合酶链式反应（real-time reverse transcription quantitative polymerase chain reaction，RT-qPCR）、Western blotting和免疫组化检测海马组织p53、SLC7A11、GPX4、ACSL4的mRNA和蛋白表达量。结果 与模型组比较，脑心通组大鼠神经功能评分减少，脑梗死率显著降低（P＜0.01），海马组织病理学改变减轻，海马组织中总铁、脂质过氧化物显著降低（P＜0.05），SLC7A11、GPX4的mRNA表达量和蛋白表达量显著增加（P＜0.01），p53、ACSL4的mRNA和蛋白表达量显著减少（P＜0.01）。p53抑制剂能够抑制p53表达，恢复大鼠神经功能，减少脑梗死率，降低铁超载，抑制铁死亡发生（P＜0.05），与脑心通胶囊有协同作用。结论 脑心通胶囊通过抑制p53进而减少大鼠脑缺血再灌注损伤中铁死亡。

Objective To investigate how Naoxintong Capsule reduces cerebral ischemia-reperfusion injury in rats by inhibiting ferroptosis. Methods Male SD rats were randomly divided into sham operation group, model group, Naoxintong (110.0 mg/kg) group, Ginaton (21.6 mg/kg) group, p53 inhibitor (25.0 mg/kg) group and p53 inhibitor (25.0 mg/kg) + Naoxintong (110.0 mg/kg) group. The cerebral ischemia-reperfusion injury rat model was prepared by transient middle cerebral artery occlusion, and the parameters were evaluated and sampled 24 h after operation. Nerve function score was used to detect nerve function. The infarct size was measured by 2,3,5-triphenyltetrazolium chloride solution (TTC). Hippocampal morphological structure was observed by hematoxylin-eosin (HE) staining. The ultrastructure was observed by transmission electron microscope. The contents of ferrous and lipid peroxides in hippocampus were detected by biochemical reagents. The mRNA and protein expression levels of p53, SLC7A11, GPX4 and ACSL4 in hippocampus were detected by RT-qPCR, Western blotting and immunohistochemistry. Results Compared with the model group, the neurological function score and cerebral infarction rate of rats in Naoxintong group were decreased (P < 0.01), the histopathological changes in hippocampus were alleviated, the total iron and lipid peroxides in hippocampus were significantly decreased (P < 0.05), and the mRNA and protein expressions of SLC7A11 and GPX4 were significantly increased (P < 0.01). The mRNA and protein expression of p53 and ACSL4 were significantly decreased (P < 0.01). p53 inhibitor can inhibit the expression of p53, restore the nervous function of rats, reduce the rate of cerebral infarction, reduce iron overload, and inhibit the occurrence of ferroptosis (P < 0.05), which has a synergistic effect with Naoxintong capsule. Conclusion Naoxintong Capsule can reduce ferroptosis in cerebral ischemia-reperfusion injury in rats by inhibiting p53.

R285.5

北京中医药大学基本科研业务费项目（揭榜挂帅项目）（2022-JYB-JBZR-005）;国家自然科学基金面上项目（81573726）