补阳还五汤干预缺血性卒中气虚血瘀证铁代谢损伤的机制  

Mechanism of Buyang Huanwu Decoction in intervening iron metabolism injury of ischemic stroke with qi deficiency and blood stasis syndrome

作　　者：吴海辉 梁祺 杨彤[1] 聂慧芳[1] 王珊珊[1] 葛金文[1,3] WU Haihui;LIANG Qi;YANG Tong;NIE Huifang;WANG Shanshan;GE Jinwen(Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases,Changsha 410208,China;Pinghu Hospital of Traditional Chinese Medicine,Pinghu 314200,China;Hunan Academy of Chinese Medicine,Changsha 410006,China)

机构地区：[1]湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室,长沙410208 [2]浙江省平湖市中医院,浙江平湖314200 [3]湖南省中医药研究院,长沙410006

出　　处：《中华中医药杂志》2023年第8期3562-3569,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81774174);湖南省自然科学基金项目(No.2022JJ40303);湖南省研究生科研创新项目(No.CX20200795);湖南省“国内一流培育学科”中西医结合开放基金项目(No.2020ZXYJH28)。

摘　　要：目的:观察补阳还五汤通过转铁蛋白(TF)-铁调素信号通路减少缺血性卒中气虚血瘀证模型大鼠的脑铁沉积,探讨补阳还五汤对脑缺血的神经保护作用。方法:48只SPF级SD雄性大鼠,随机分为假手术组、模型组、补阳还五汤组和去铁酮组。采用持续力竭性游泳复合改良线栓法制备缺血性卒中气虚血瘀证模型。比较各组大鼠的一般情况和神经功能评分;运用HE染色、TTC染色、尼氏染色和高尔基银染观察脑缺血侧组织病理形态学改变、脑梗死体积、完整神经元数量和树突形态密度;普鲁士蓝染色检测脑缺血侧铁沉积;ELISA检测血浆中白细胞介素(IL)-6和肿瘤坏死因子-α(TNF-α)的含量;Western Blot和免疫荧光检测脑缺血侧TF-铁调素通路相关蛋白的表达水平。结果:与模型组比较,补阳还五汤组和去铁酮组大鼠精神状态、活动度、左侧肢体运动功能相对改善,神经功能评分显著下降(P<0.05,P<0.01),脑梗死体积显著减少(P<0.01),血浆中TNF-α和IL-6水平显著降低(P<0.01),铁沉积颗粒相对减少,尼氏小体数目显著增多(P<0.01),树突棘密度显著增加(P<0.01);TF、TFR、p-Smad1/5/8和铁调素蛋白相对表达与免疫荧光强度均显著下降(P<0.01,P<0.05)。结论:补阳还五汤可通过抑制TF-铁调素通路减少铁调素表达,促进铁输出,发挥改善脑缺血铁沉积损伤的作用。Objective:To observe the effect of Buyang Huanwu Decoction on reducing brain iron deposition in ischemic stroke model rats with qi deficiency and blood stasis syndrome and to explore its effect on transferrin(TF)-Hepcidin signaling pathway.Methods:Forty-eight SD male rats were randomly divided into 4 groups:sham group,model group,Buyang Huanwu Decoction group(BHT)and Deferiprone Tablets group(DFP).The model of qi deficiency and blood stasis syndrome of ischemic stroke was prepared by continuous exhaustion swimming combined with improved Zea Longa wire occlusion method.The general situation and neurological function score of each group were compared;HE staining,TTC staining,Nissl staining and Golgicox staining were used to observe the pathological changes,infarct volume,number of intact neurons,dendritic morphology and dendritic spine density of cerebral ischemia side of rats in each group.Perls staining was used to detect the iron deposition in ischemic side brain tissue of rats in each group.The contents of interleukin(IL)-6 and tumor necrosis factor-α(TNF-α)in plasma were detected by ELISA.Western Blot and immunofluorescence were used to detect the expression levels of proteins related to the TF-Hepcidin pathway on the ischemic side of the brain.Results:Compared with model group,neurological function score of BHT group and DFP group showed a downward trend(P<0.05,P<0.01),and cerebral infarction volume was significantly decreased(P<0.01),and there was no statistical significance in cerebral infarction volume between the two groups,and the plasma levels of TNF-αand IL-6 in model group were increased to varying degrees(P<0.01),and iron deposition particles were relatively decreased,the numbers of Nissl body were increased significantly(P<0.01).The number and density of dendrite spines were significantly increased(P<0.01).The relative expressions immunofluorescerce intensity of TF,TFR,p-Smad1/5/8 and Hepcidin were significantly decreased in cerebral ischemia cortex(P<0.01,P<0.05).Conclusion:Buyang Huanwu Decocti

关 键 词：补阳还五汤 缺血性卒中 气虚血瘀证 铁代谢 铁调素通路 

分 类 号：R285.5[医药卫生—中药学]