目的 探討腦心通膠囊通過抑制鐵死亡減少大鼠腦缺血再灌注損傷。方法 雄性SD大鼠隨機分為假手術(shù)組、模型組、腦心通（110.0 mg/kg）組、金納多（21.6 mg/kg）組、p53抑制劑（25.0 mg/kg）組和p53抑制劑（25.0 mg/kg）＋腦心通（110.0 mg/kg）組。通過短暫性大腦中動脈閉塞制備腦缺血再灌注損傷大鼠模型，術(shù)后24 h進行指標評定及取材，評估各組大鼠神經(jīng)功能評分檢測神經(jīng)功能；2,3,5-三苯基氯化四氮唑（2,3,5-triphenyltetrazolium chloride solution，TTC）法檢測腦梗死面積；蘇木素-伊紅（hematoxylin-eosin，HE）染色觀察海馬形態(tài)結(jié)構(gòu)；透射電鏡觀察超微結(jié)構(gòu)；生化試劑檢測海馬組織亞鐵、脂質(zhì)過氧化物含量；逆轉(zhuǎn)錄實時定量聚合酶鏈式反應(yīng)（real-time reverse transcription quantitative polymerase chain reaction，RT-qPCR）、Western blotting和免疫組化檢測海馬組織p53、SLC7A11、GPX4、ACSL4的mRNA和蛋白表達量。結(jié)果 與模型組比較，腦心通組大鼠神經(jīng)功能評分減少，腦梗死率顯著降低（P＜0.01），海馬組織病理學改變減輕，海馬組織中總鐵、脂質(zhì)過氧化物顯著降低（P＜0.05），SLC7A11、GPX4的mRNA表達量和蛋白表達量顯著增加（P＜0.01），p53、ACSL4的mRNA和蛋白表達量顯著減少（P＜0.01）。p53抑制劑能夠抑制p53表達，恢復大鼠神經(jīng)功能，減少腦梗死率，降低鐵超載，抑制鐵死亡發(fā)生（P＜0.05），與腦心通膠囊有協(xié)同作用。結(jié)論 腦心通膠囊通過抑制p53進而減少大鼠腦缺血再灌注損傷中鐵死亡。

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

北京中醫(yī)藥大學基本科研業(yè)務(wù)費項目（揭榜掛帥項目）（2022-JYB-JBZR-005）;國家自然科學基金面上項目（81573726）