李氏5号中药对D-半乳糖老化小鼠海马超微结构及胰岛素受体底物表达的影响  

Effect of Chinese drug Lishi No.5 on the ultrastructure of hippocampal neurons and expression of insulin receptor substrate in D-galactose induced aging mice

作　　者：姚洁[1] 李子中 赵志炜[1] 程浩然 姬志娟[1] 闵嵘[1] 孙异临[3] 盛树力[1] 

机构地区：[1]首都医科大学宣武医院北京脑老化重点实验室,北京市100053 [2]高明脑病医疗研究院,广东省高明市528500 [3]北京神经外科研究所,北京市100050

出　　处：《中国临床康复》2004年第31期6966-6967,i004,共3页Chinese Journal of Clinical Rehabilitation

摘　　要：目的:观察李氏5号中药对D-半乳糖老化小鼠海马超微结构和磷脂酰肌醇酯3激酶(phosphatidylinoditide-3'OHkinase,PI3K)、胰岛素受体底物-1(insulin-receptorsubstrate-1,IRS-1)、胰岛素受体底物-2(insulinreceptorsubstrate-2,IRS-2)表达的影响。方法:将132只小鼠随机分为6组,正常对照(C)组、D-半乳糖模型(D)组、李氏5号大剂量(L)组、中剂量(M)组、小剂量(S)组、多奈哌齐(A)组。D,L,M,S,A5组每日皮下注射半乳糖100mg/kg。L,M,S3个治疗组分别灌胃李氏5号方1.2,0.6,0.3g/(kg·d),A组多奈哌齐0.75mg/(kg·d)灌胃。4个月后,取小鼠海马CA1区组织进行电镜观察,行脑冷冻切片,用PI3K,IRS-1,IRS-2抗体进行免疫组化染色。结果:①电镜结构显示,D-半乳糖老化小鼠海马CA1区神经元核固缩,线粒体、高尔基体等细胞器肿胀,血管足突细胞肿胀,管腔变窄;李氏5号中药保护可以明显改善这种现象。②免疫组织化学染色结果显示3种抗体C组深染的阳性细胞在海马广泛分布,D组海马阳性反应细胞着色浅,少有突起,细胞数目少,分别为C组的48.8%,57.0%和60.8%。李氏5号方组染色结果与C组相似,A组亦有相同结果。结论:D-半乳糖老化小鼠海马CA1区出现明显超微结构病理改变,海马PI3K,IRS-1,IRS-2的表达明显下降;李氏5号中药保护能明显改善CA1区?AIM:To investigate the influence of Lishi No.5 on the ultrastructure of hippocampus and the expression of phosphatidyl inoditide-3'OH kinase(PI3K),insulin receptor substrate-1(IRS-1) and insulin receptor substrate-2(IRS-2) in D-galactose induced aging of murine(DGAM). METHODS:A total of 132 Kunming mice were randomly divided into 6 groups: normal control group,DGAM group,Lishi No.5 large,middle and small dose groups,aricept group.The mice in the DGAM group,Lishi No.5 large,middle and small dose groups and aricept group were injected with D-galactose 100 mg/kg subcutaneously everyday,besides,the mice in the Lishi No.5 large,middle and small dose groups received gastric perfusion of Lishi No.5 at the dose of 1.2,0.6 and 0.3 g/kg per day respectively,while those in the aricept group were treated with gastric perfusion of aricept 0.75 mg/kg per day.After 4 months,the CA1 area of the mice hippocampus was taken and observed by electron microscope,frozen sections of brain were prepared,and then PI3K,IRS-1 and IRS-2 were stained with immunohistochemistry. RESULTS:①The results of electron microscope showed that in the DGAM group there was pyknosis in the CA1 hippocampus neuron,swelling of mitochondyia,Golgi body and other organells;edema of vascular foot processes and narrowed vascular lumen were also observed.The above phenomena could be obviously ameliorated by Lishi No.5.②The results of immunohistochemical staining showed that in the control group the deeply stained positive cells were distributed widely in the hippocampus,the hippocampal positive cell were stained slightly,there was seldom process and fewer cells in the DGAM group, which were 48.8%,57.0%and 60.8%of those in the control group,while the results of staining in the Lishi No.5 groups were similar to that in the control group,and there was the same result in the aricept group. CONCLUSION:There is obvious pathological change of the ultrastructure in the hippocampal CA1 of DGAM,and the expressions of PI3K,IRS-1 and IRS-2 are obviously decreased.The Chi

关 键 词：D-半乳糖 小鼠 海马 表达 超微结构 中药 IRS-1 李氏 相同 

分 类 号：R285.5[医药卫生—中药学] R392[医药卫生—中医学]