中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (4): 873-881.doi: 10.12307/2025.992

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

雷公藤内酯酮抑制铁死亡改善大脑动脉闭塞/再灌注模型大鼠脑缺血再灌注损伤

邹荣基1，喻芳芳2，王茂林1，贾卓鹏1    

  1. 西安医学院第一附属医院，1神经外科，2神经内科，陕西省西安市  710077

  • 收稿日期:2024-08-29 接受日期:2024-11-30 出版日期:2026-02-08 发布日期:2025-05-19
  • 通讯作者: 贾卓鹏，硕士，副主任医师，西安医学院第一附属医院神经外科，陕西省西安市 710077
  • 作者简介:邹荣基，男，硕士，主治医师，主要从事脑血管、脑肿瘤等疾病诊治方面的研究。 共同第一作者：喻芳芳，女，硕士，主治医师，主要从事脑血管、脑肿瘤等疾病诊治方面的研究。
  • 基金资助:
    西安市未央区科工局科研资金资助项目(202023)，项目参与人：邹荣基

Triptolide inhibits ferroptosis and improves cerebral ischemia-reperfusion injury in a rat model of cerebral artery occlusion/reperfusion

Zou Rongji1, Yu Fangfang2, Wang Maolin1, Jia Zhuopeng1   

  1. 1Department of Neurosurgery, 2Department of Neurology, The First Affiliated Hospital of Xi’an Medical University, Xi’an 710077, Shaanxi Province, China
  • Received:2024-08-29 Accepted:2024-11-30 Online:2026-02-08 Published:2025-05-19
  • Contact: Jia Zhuopeng, Master, Associate chief physician, Department of Neurosurgery, The First Affiliated Hospital of Xi’an Medical University, Xi’an 710077, Shaanxi Province, China
  • About author:Zou Rongji, Master, Attending physician, Department of Neurosurgery, The First Affiliated Hospital of Xi’an Medical University, Xi’an 710077, Shaanxi Province, China Yu Fangfang, Master, Attending physician, Department of Neurology, The First Affiliated Hospital of Xi’an Medical University, Xi’an 710077, Shaanxi Province, China Zou Rongji and Yu Fangfang contributed equally to this work.
  • Supported by:
    Science and Industry Bureau of Weiyang District, Xi’an City, No. 202023 (to ZRJ [project participant]) 

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摘要：


文题释义：
雷公藤内酯酮：为一种从雷公藤中分离得到的枞烷型二萜类化合物，具有显著的药理活性，这种草药已在传统中医中使用了上百年。研究表明它具有抗氧化、抗类风湿、抗老年性痴呆症、抗癌等功效，用于多种疾病的治疗。
脑缺血再灌注损伤：是指脑组织动脉循环急性栓塞之后，供血恢复引起的缺血性脑损伤二次损伤，是直接引起脑梗死并降低脑缺血患者预后的主要原因。它是一个极其复杂的病理过程，临床上具有高致残率和致死率的特点。

背景：雷公藤内酯酮作为中药雷公藤的生物活性成分对神经元具有一定的保护作用。
目的：探讨雷公藤内酯酮对脑缺血再灌注损伤的影响。
方法：①细胞实验：将海马神经元(HT22细胞)随机分为对照组、糖氧剥夺/复氧组、糖氧剥夺/复氧+雷公藤内酯酮组、糖氧剥夺/复氧+雷公藤内酯酮+敲低TP53诱导的糖酵解和凋亡因子(si-TIGAR)组、糖氧剥夺/复氧+si-TIGAR组、糖氧剥夺/复氧+雷公藤内酯酮+雷帕霉素组。通过CCK-8法检测HT22细胞活力，Western blotting检测TIGAR、谷胱甘肽过氧化酶4、溶质载体家族7成员11、鞘氨醇激酶1和哺乳动物雷帕霉素靶蛋白的蛋白表达水平，生化试剂盒检测谷胱甘肽、丙二醛含量和亚铁离子的水平。②动物实验：将大鼠随机分为假手术组、模型组、雷公藤内酯酮组，后两组制备大脑动脉闭塞/再灌注大鼠模型，雷公藤内酯酮组于建模后采用50 mg/kg雷公藤内酯酮灌胃7 d。给药结束后
24 h，采用LONGA法评估大鼠神经功能缺损情况，TTC法观察脑组织梗死情况，TUNEL染色检测凋亡水平，Western blotting检测凋亡相关蛋白表达水平。
结果与结论：①在细胞水平，与对照组比较，雷公藤内酯酮可恢复糖氧剥夺/复氧处理HT22细胞的活力，抑制细胞凋亡，上调HT22细胞中TIGAR、谷胱甘肽过氧化酶4、溶质载体家族7成员11的表达水平，激活SPHK1/mTOR通路；此外，雷公藤内酯酮还可升高谷胱甘肽含量，降低丙二醛含量和亚铁离子水平；而雷帕霉素处理抵消了雷公藤内酯酮对HT22细胞的保护作用；②在动物水平，雷公藤内酯酮明显降低了模型组大鼠脑组织的神经功能缺损、梗死体积和细胞凋亡，并抑制模型组大鼠神经元铁死亡；③提示雷公藤内酯酮通过上调TIGAR表达水平，激活SPHK1/mTOR信号来抑制铁死亡，从而减轻脑缺血再灌注损伤。结果提示，雷公藤内酯酮可能是脑缺血再灌注损伤治疗的候选药物。
https://orcid.org/0009-0008-3839-5278(邹荣基)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 雷公藤内酯酮, 铁死亡, TIGAR, 哺乳动物雷帕霉素靶蛋白, 脑缺血再灌注损伤, 工程化组织构建

Abstract: BACKGROUND: Triptolide, a bioactive component of the traditional Chinese medicine Tripterygium wilfordii, has a certain protective effect on neurons. 
OBJECTIVE: To investigate the effect of triptolide on cerebral ischemia/reperfusion injury. 
METHODS: (1) Cell experiment: Hippocampal neurons (HT22 cells) were randomly divided into control group, glucose oxygen deprivation/reoxygenation (OGD/R) group, OGD/R+triptolide group, OGD/R+triptolide+si-TIGAR group, OGD/R+si-TIGAR group, and OGD/R+triptolide+rapamycin group. HT22 cell viability was detected by cell counting kit 8. Tp53-induced glycolysis and apoptosis factors, glutathione peroxidase 4, 7 members of the solsolic vector family 11, sphingosine kinase 1 (SPHK1) and (mTOR) were detected by western blot assay. Glutathione, malondialdehyde and iron level were detected using the biochemical kit. (2) Animal experiment: Rats were randomly divided into sham surgery group, model group, and triptolide group. Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups. Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days. Twenty-four hours after administration, LONGA method was used to evaluate the neurological impairment of rats, TTC method was used to observe the conditions of cerebral infarction, TUNEL staining was used to detect cell apoptosis, and western blot was performed to detect the expression level of related proteins. 
RESULTS AND CONCLUSION: (1) At the cellular level, triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R. Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors, glutathione peroxidase 4, and 7 members of the solsolic vector family 11, activated the SPHK1/mTOR pathway, increased glutathione content, inhibited malondialdehyde content and iron levels. Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells. (2) At the animal level, triptolide significantly reduced neurological deficits, infarct volume, and cell apoptosis, and inhibited neuronal ferroptosis in brain tissue of rats. To conclude, triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling, and thereby reduced cerebral ischemia/reperfusion injury. These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

Key words: triptolide, ferroptosis, TIGAR, mammalian target of rapamycin, cerebral ischemia/reperfusion injury, engineered tissue construction

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