心脑舒通胶囊抑制铁死亡减轻大鼠脑缺血再灌注损伤的机制  

Mechanism of Xinnao shutong capsule alleviating cerebral ischemia-reperfusion injury in rats by regulating ferroptosis

作　　者：李华妮 刘长河 郭晓燕 钟鑫 张薇 葛文静 LI Huani;LIU Changhe;GUO Xiaoyan;ZHONG Xin;ZHANG Wei;GE Wenjing(Academy of Chinese Medicine,Henan Integrative Medicine Hospital,Zhengzhou 450004,China;Henan Engineering Research Center of Traditional Chinese Medicine Preparation,Zhengzhou 450004,China;Dept.of Pharmacy,Zhengzhou Cigarette Factory Rehabilitation Hospital,Zhengzhou 450047,China)

机构地区：[1]河南省中西医结合医院中药研究所,郑州450004 [2]河南省中药制剂工程技术研究中心,郑州450004 [3]郑州卷烟厂康复医院药剂科,郑州450047

出　　处：《中国药房》2025年第3期306-311,共6页China Pharmacy

基　　金：河南省自然科学基金项目(No.232300421318);河南省中医药科学研究专项课题(No.2022ZY1148);河南省基本科研业务费(No.2304013,No.2404044)。

摘　　要：目的 研究心脑舒通胶囊调控铁死亡途径减轻大鼠脑缺血再灌注损伤(CIRI)的机制。方法 将大鼠随机分为假手术组,模型组,心脑舒通低、高剂量组(220、440 mg/kg),银杏叶提取物组(阳性对照,150 mg/kg)。各组大鼠灌胃相应药液/生理盐水,连续7 d。采用短暂性大脑中动脉闭塞法复制CIRI模型,术后24 h进行取材,检测大鼠脑梗死面积,并计算脑梗死率;观察大鼠脑组织病理学变化;检测大鼠脑组织中总铁和血清中脂质过氧化物(LPO)、丙二醛(MDA)、谷胱甘肽(GSH)水平;检测大鼠脑组织中核转录因子红系2相关因子2(Nrf2)/血红素氧合酶1(HO-1)/谷胱甘肽过氧化物酶4(GPX4)蛋白和mRNA表达水平。结果 与模型组比较,银杏叶提取物组和心脑舒通各剂量组大鼠脑梗死率、脑组织中总铁水平、血清中LPO水平(银杏叶提取物组和心脑舒通低剂量组除外)均显著降低(P<0.05或P<0.01);血清中GSH水平以及脑组织中Nrf2、HO-1、GPX4蛋白和mRNA表达水平均显著升高(P<0.05或P<0.01);脑组织病理损伤减轻,神经细胞数目增多,水肿减轻,核膜平整。结论 心脑舒通胶囊可抑制铁死亡,减轻CIRI,其作用机制可能与激活Nrf2/HO-1/GPX4信号通路有关。OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury(CIRI)in rats by regulating the ferroptosis pathway.METHODS SD rats were randomly divided into sham operation group,model group,Xinnao shutong low-dose,high-dose group(220,440 mg/kg),Ginkgo biloba leaves extract group(positive control,150 mg/kg).Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days.Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model;the samples were taken 24 h after the operation;the cerebral infarction area of rats was detected,and the cerebral infarction rate was calculated.The pathological changes of brain tissues were observed,and the levels of lipid peroxide(LPO),malondialdehyde(MDA)and glutathione(GSH)in cerebral tissue were detected;mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1)and glutathione peroxidase 4(GPX4)were all detected in cerebral tissue of rats.RESULTS Compared with model group,the cerebral infarction rate,the content of total iron in cerebral tissue and serum level of LPO(except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group)were all decreased significantly in G.biloba leaves extract group and Xinnao shutong groups(P<0.05 or P<0.01);the serum level of GSH,the protein and mRNA expressions of Nrf2,HO-1 and GPX4 were all increased significantly(P<0.05 or P<0.01).The pathological damage to brain tissue was reduced,the number of nerve cells increased,the edema was alleviated,and the nuclear membrane was flattened.CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI,the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.

关 键 词：心脑舒通胶囊 脑缺血再灌注损伤 铁死亡 Nrf2/HO-1/GPX4信号通路 

分 类 号：R965[医药卫生—药理学]