天麻素抑制铁死亡改善血管性痴呆大鼠神经损伤及认知功能  

Gastrodin improves neurological damage and cognitive function by inhibiting ferroptosis in rats with vascular dementia

作　　者：陈婷婷 苏杭 杨红[1] 刘佳[1] 张宝[1] 陈永鑫 陶玲[2] 沈祥春[2] 李悦 CHEN Tingting;SU Hang;YANG Hong;LIU Jia;ZHANG Bao;CHEN Yongxin;TAO Ling;SHEN Xiangchun;LI Yue(Department of Pharmacy,Maternal and Child Health Care Hospital Affiliated to Guizhou Medical University,Guiyang 550003,Guizhou,China;Key Laboratory of Optimal Utilization of Natural Medicine Resources,Guizhou Medical University,Guiyang 550025,Guizhou,China)

机构地区：[1]贵州医科大学附属妇女儿童医院药学部,贵州贵阳550003 [2]贵州医科大学天然药物资源优效利用重点实验室,贵州贵阳550025

出　　处：《贵州医科大学学报》2024年第7期982-987,1041,共7页Journal of Guizhou Medical University

基　　金：贵阳市卫生健康局科学技术计划项目(〔2022〕016);贵州省科技厅科技计划项目(黔科合基础-ZK〔2024〕一般595);贵州省高层次创新型人才十层次人才项目(GCC〔2023〕048);贵州特色药用资源优效利用研究创新基地中央引导地方基金(〔2023〕003);贵州省卫生健康委科学技术基金项目(Gzwkj2023-084)。

摘　　要：目的探讨天麻素对血管性痴呆(VaD)大鼠海马细胞铁死亡的影响及机制。方法60只雄性SD大鼠随机均分为假手术组、模型组、天麻素低剂量组(25 mg/kg)、高剂量组(50 mg/kg)和阳性药多奈哌齐组(2 mg/kg),模型组、天麻素低剂量组、天麻素高剂量组和阳性药多奈哌齐组通过永久性大脑中动脉闭塞法建立VaD大鼠模型,假手术组除不闭塞大脑中动脉外其余操作同模型组;建模后1周后,各给药组大鼠灌胃给药,模型组和假手术组大鼠灌胃相应体积蒸馏水,连续给药8周;采用Morris水迷宫实验记录各组大鼠逃避潜伏期、穿越平台次数;水迷宫实验结束时,取各组大鼠海马组织检测丙二醛(MDA)、还原型谷胱甘肽(GSH)和Fe^(2+)的含量,免疫印迹和免疫组化检测铁死亡标志性蛋白GPX4和COX2的蛋白表达。结果与模型组比较,天麻素高剂量组与阳性药多奈哌齐组的逃避潜伏显著缩短(P<0.05),穿过平台的次数显著增加(P<0.05);与模型组比较,天麻素高剂量组与阳性药多奈哌齐组大鼠海马区的MDA与Fe^(2+)的水平降低(P<0.05),GSH的活力升高(P<0.05);与模型组比较,天麻素高剂量组与阳性药多奈哌齐组海马组织中GPX4蛋白表达显著上调(P<0.05),COX2显著下调(P<0.05)。结论天麻素可改善VaD模型大鼠的学习记忆能力,其机制可能与减少大鼠海马中Fe^(2+)蓄积,抑制海马细胞铁死亡,保护VaD大鼠海马神经元有关。Objective To investigate the effect of gastrodin on hippocampal cell ferroptosis of rats with vascular dementia(VaD)and its mechanism.Methods Sixty male SD rats were randomly divided into sham group,model group,low-dose gastrodin group(25 mg/kg),high-dose gastrodin group(50 mg/kg)and donepezil group(2 mg/kg,positive control).Rat VaD model was established by permanent middle cerebral artery occlusion in model group,low-dose gastrodin group,high-dose gastrodin group and donepezil group.Sham group was given the same procedures as model group except for not occluding the middle cerebral artery.At 1 week after modeling,the rats in each treatment group were intragastrically administered,while model group and sham group were intragastrically administered with corresponding volumes of distilled water.The treatment lasted for 8 consecutive weeks.Morris water maze was performed to record the escape latency and the times of crossing platforms in each group.At the end of Morris water maze,the contents of malondialdehyde(MDA),reduced glutathione(GSH),and Fe^(2+)in rat the hippocampal tissues in each group were detected,and the protein expressions of ferroptosis marker proteins GPX4 and COX2 were detected by Western blot and immunohistochemistry.Results When compared with model group,high-dose gastrodin and donepezil groups had significantly shorten escape latency(P<0.05)and increased times of crossing platforms(P<0.05).When compared with model group,high-dose gastrodin and donepezil groups had decreased levels of MDA and Fe^(2+)in rat hippocampi(P<0.05)and increased GSH activity(P<0.05).When compared with model group,high-dose gastrodin and donepezil groups had significantly upregulated GPX4 protein expression and downregulated COX2 protein expression.Conclusion Gastrodin can improve the learning and memory ability of rat with VaD model,and its mechanism may be related to the reduction of Fe^(2+)accumulation in rat hippocampi,the inhibition of hippocampal cell ferroptosis,and the protection of hippocampal neurons in rats with

关 键 词：天麻素 血管性痴呆 铁死亡 谷胱甘肽过氧化酶4 环氧化酶2 

分 类 号：R338.6[医药卫生—人体生理学] R962[医药卫生—基础医学]