葛根汤改善大鼠脑缺血再灌注损伤及机制研究  

Study on the Improvement of Cerebral Ischemia-Reperfusion Injury and Its Mechanism in Rats by Gegen Decoction

作　　者：黄丽贤[1] 李红艳 范庆菁[1] 吴兢[1] 李群先 裴雪梅 马洪明[1] 李庆彬[1] 邹忆怀[1] HUANG Lixian;LI Hongyan;FAN Qingjing;WU Jing;LI Qunxian;PEI Xuemei;MA Hongming;LI Qingbin;ZOU Yihuai(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 101121,China)

机构地区：[1]北京中医药大学东直门医院,北京101121

出　　处：《中国中医基础医学杂志》2025年第4期639-643,共5页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药人教函〔2022〕1号);北京市通州区高层次人才发展支持计划领军人才项目(YHLD2019019)。

摘　　要：目的研究葛根汤对大鼠脑缺血再灌注损伤的神经保护作用,并分析其潜在的作用机制。方法选用SPF级雄性SD大鼠,建立左侧短暂性大脑中动脉栓塞(tMCAO)模型,造模成功后随机分为模型组,葛根汤低、中、高剂量组与依达拉奉组,另设假手术大鼠为对照组。各组以相应药物灌胃5天后,测定神经功能评分;TTC染色检测脑梗死面积;透射电子显微镜下观察线粒体形态;HE染色观察脑组织神经元的细胞形态结构及病理形态学改变;比色法检测血清中活性氧(ROS)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)水平;Western blot检测氨基酸-谷胱甘肽代谢通路溶质载体家族7成员11(SLC7A11)/溶质载体家族3成员2(SLC3A2)/谷胱甘肽过氧化物酶4(GPX4)蛋白表达。结果与模型组比较,不同剂量葛根汤组及依达拉奉组大鼠的神经功能明显改善(P<0.01),脑梗死面积下降,线粒体损伤减轻,脑水肿、炎性细胞浸润及细胞坏死均有改善;与模型组比较,葛根汤中、高剂量及依达拉奉组SOD、GSH显著升高(P<0.05),ROS水平显著降低(P<0.01),GPX4、SLC3A2、SLC7A11蛋白表达显著增加(P<0.05)。结论葛根汤可以改善大鼠脑缺血再灌注损伤,其作用机制可能与铁死亡有关。Objective To study the neuroprotective effect of Gegen decoction on cerebral ischemia-reperfusion injury in rats and analyze its potential mechanisms.Methods SPF-grade male SD rats were selected to establish a left transient middle cerebral artery occlusion(t-MCAO)model.After successful modeling,the rats were randomly divided into a model group,low,medium,and high dose Gegen decoction groups,and an Edaravone group,with a sham-operated group as the control.After 5 days of corresponding drug administration via gavage,neurological function scores were measured;TTC staining was used to detect the area of cerebral infarction;mitochondrial morphology was observed under a transmission electron microscope;HE staining was used to observe the cellular morphology and pathological changes of neurons in brain tissue;colorimetric methods were used to detect levels of reactive oxygen species(ROS),superoxide dismutase(SOD),and glutathione(GSH)in serum;and Western blot was used to detect the expression of solute carrier family 7 member 11(SLC7A11)/solute carrier family 3 member 2(SLC3A2)/glutathione peroxidase 4(GPX4)proteins in the amino acid-glutathione metabolic pathway.Results Compared with the model group,the different doses of Gegen decoction and edaravone groups showed significant improvement in neurological function in rats(P<0.01),a decrease in cerebral infarction area,reduced mitochondrial damage,and improvements in brain edema,inflammatory cell infiltration,and cell necrosis;compared with the model group,the levels of SOD and GSH in the high and medium doses of Gegen decoction and edaravone groups were significantly increased(P<0.05),while ROS levels were significantly decreased(P<0.01),and the protein expressions of GPX4,SLC3A2,and SLC7A11 were significantly increased(P<0.05).Conclusion Gegen decoction can improve cerebral ischemia-reperfusion injury in rats,and its mechanism of action may be related to ferroptosis.

关 键 词：脑缺血再灌注损伤 葛根汤 铁死亡 大鼠 

分 类 号：R285[医药卫生—中药学]