摘要
目的探讨黄芪甲苷(astragaloside IV,AST)对血管性痴呆(vascular dementia,VD)大鼠的保护作用及其机制。方法50只雄性SD大鼠随机分为假手术组、VD模型组、AST组(5、15、45 mg/kg)。采用腹腔注射硝普钠降压后立即夹闭双侧颈总动脉10 min、随后再通10 min、再夹闭10 min的方式制备VD模型。AST组于缺血前12、2 h2次灌胃AST,各组剂量分别为5、15、45 mg/kg。于术后第7天开始进行水迷宫实验测定大鼠学习记忆能力。水迷宫实验结束后取大鼠海马测试;HPLC法测定海马还原型谷胱甘肽含量;免疫组化法观察海马CA1区胶质纤维酸性蛋白(GFAP)表达;Western Blot方法检测磷酸化NF-κB P65(p-NF-κB P65)蛋白的含量变化;ELISA法检测海马组织中IL-1β、TNF-α含量。结果与假手术组相比较,模型组大鼠学习记忆能力明显下降,脑海马组织中GSH含量降低,GFAP与p-NF-κB P65表达增加(P<0.01)。与模型组相比,AST各组学习记忆能力明显提高,海马组织中GSH含量增加(P<0.01),GFAP和p-NF-κB P65表达下降(P<0.01)。结论AST对大鼠VD具有保护作用,其作用机制可能与增加大鼠海马组织中的GSH含量,提高了大鼠抗氧化能力,抑制星形胶质细胞的过度活化,进而抑制NF-κB途径的异常激活,减少炎症细胞因子IL-1β和TNF-α表达有关。
Objective To investigate the protective effect and mechanism of astragaloside IV(AST)on rats with vascular dementia(VD).Methods 50 male SD rats were randomly divided into the sham operation group,the VD model group and AST group(5,15,45 mg/kg).The VD model was prepared by clamping bilateral common carotid arteries for 10 min immediately after intraperitoneal injection of sodium nitroprusside to reduce blood pressure,followed by another 10 min of ventilation and another 10 min of clamping.AST group was given intragastric administration twice 12 and 2 h before ischemia,and the doses were 5,15 and 45 mg/kg,respectively.The learning and memory ability of rats was measured by water maze experiment on the 7th day after operation.After the water maze experiment,hippocampal test was taken from rats;the content of reduced glutathione in hippocampus was determined by HPLC;the expression of glial fibrillary acid protein(GFAP)in hippocampal CA1 region was observed by immunohistochemistry;the content of phosphorylated NF-κB P65(p-NF-κB P65)protein was detected by Western Blot;the contents of IL-1βand TNF-αin hippocampus tissue were determined by ELISA.Results Compared with sham operation group,the learning and memory ability of rats in model group was significantly decreased,the content of GSH in brain equine tissue was decreased,and the expression of GFAP and p-NF-κB P65 was increased(P<0.01).Compared with model group,the learning and memory ability of AST group was significantly improved,the content of GSH in hippocampus was increased(P<0.01),and the expression of GFAP and p-NF-κB P65 was decreased(P<0.01).Conclusion AST has a protective effect on VD in rats,and its mechanism may be related to increasing the content of GSH in the hippocampus of rats,improving the antioxidant capacity of rats,inhibiting the over-activation of astrocytes,inhibiting the abnormal activation of NF-κB pathway,and reducing the expression of inflammatory cytokines IL-1βand TNF-α.
作者
杨文强
卢金莹
于露
王高
杨菁
Yang Wenqiang;Lu Jinying;Yu Lu;Wang Gao;Yang Jing(The Public Laboratory Platform of Institue of Life Sciences,Jinzhou Medical University,Jinzhou 121000 China)
出处
《锦州医科大学学报》
CAS
2023年第4期12-16,共5页
Journal of Jinzhou Medical University
基金
辽宁省教育厅面上项目,项目编号:2021LJKZ0823
大学生创新训练项目,项目编号:202010160126。
