摘要
【目的】建立胰岛素抵抗状态下的阿尔茨海默病(AD)大鼠模型。【方法】选用胰岛素抵抗OLETF大鼠8只为OLETF组,同品系LETO正常大鼠8只为LETO组。16只OLETF大鼠采用腹腔注射D-半乳糖联合灌胃三氯化铝(AlCl3)溶液的方法复制AD模型,后随机选8只作为AD-OLETF组。造模结束后,采用Morris水迷宫实验观察各组大鼠行为学变化,应用葡萄糖测试盒检测各组大鼠血浆空腹血糖(FPG),酶联免疫吸附分析(ELISA)检测各组大鼠血浆空腹胰岛素(FINS)、血清C肽(C-P)、脑脊液胰岛素(INS),海马组织、脑脊液中β-淀粉样蛋白(Aβ)和Tau蛋白,海马组织β淀粉样前体蛋白(APP)、β位点APP内切酶1(BACE1)、早老素1(PS1)含量。【结果】与LETO组和OLETF组比较,AD-OLETF组逃避潜伏期延长(P<0.01),空间探索实验的穿越平台象限时间缩短(P<0.01)。与LETO组比较,OLETF组和AD-OLETF组大鼠血浆FPG、FINS,血清C-P含量均显著升高(P<0.01),脑脊液INS含量降低(P<0.01)。与LETO组和OLETF组比较,AD-OLETF组大鼠海马组织和脑脊液中Aβ含量,海马组织中Tau及APP、BACE1、PS1蛋白含量均显著升高(P<0.01)。【结论】以胰岛素抵抗模型OLETF大鼠为基础对象,运用D-半乳糖和AlCl3联合干预,可成功建立一种兼具胰岛素抵抗和AD主要病理特征的复合大鼠模型。
Objective To establish a rat model of Alzheimer’s disease(AD)with insulin resistance. Methods Eight insulin resistance OLETF rats were selected as OLETF group,and 8 normal LETO rats were selected as LETO group. Another 16 OLETF rats were induced into AD model by intraperitoneal injection of D-galactose combined with intragastric administration of AlCl3,and then 8 AD model rats were randomly selected as AD-OLETF group.Morris water maze test was performed to observe the behavior of the rats in each group. The fasting plasma glucose(FPG)level was determined by glucose kit. The contents of fasting insulin(FINS)in plasma,C-peptide(C-P)in serum, insulin in cerebrospinal fluid,β-amyloid(Aβ)and Tau in hippocampus tissue and cerebrospinal fluid, and amyloid β-protein precursor(APP),β-site APP-cleaving enzyme 1(BACE1)and presenilin 1(PS1)in hippocampus tissue of the rats in various groups were detected by enzyme-linked immunosorbent assay(ELISA). Results Compared with the LETO group and OLETF group,the escape latency of AD-OLETF group was prolonged(P<0.01)and the time of traversing platform quadrant was shortened(P<0.01). Compared with the LETO group, the contents of FPG, plasma FINS and C-P in the OLETF group and AD-OLETF group were significantly increased(P<0.01), and the content of insulin in cerebrospinal fluid was decreased(P<0.01,particularly in the AD-OLETF group). Compared with the LETO group and OLETF group,the contents of Aβ in the hippocampus tissue and cerebrospinal fluid and Tau,APP,BACE1,and PS1 in the hippocampus tissue of the AD-OLETF group were significantly increased(P<0.01). Conclusion A complicated AD rat model with insulin resistance was successfully established by combined intervention of D-galactose and AlCl3 based on OLETF rats.
作者
张梁
黄新宇
黄康柏
白东艳
郝燕
吴清龙
ZHANG Liang;HUANG Xin-Yu;HUANG Kang-Bai;BAI Dong-Yan;HAO Yan;WU Qing-Long(Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University ofChinese Medicine, Guangzhou 510006 Guangdong, China)
出处
《广州中医药大学学报》
CAS
2019年第10期1632-1637,共6页
Journal of Guangzhou University of Traditional Chinese Medicine
基金
国家自然科学基金资助项目（编号：81303043）
